Trial Outcomes & Findings for A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia (NCT NCT01179217)

Last Updated: 2020-08-19

Results Overview

The number of occurrences of protocol-defined sickle cell crises that occur from Week 0 to Week 48 will be used to evaluate the efficacy of oral L-glutamine as a treatment for sickle cell anemia and beta-0 thalassemia.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

230 participants

Primary outcome timeframe

48 weeks

Results posted on

2020-08-19

Participant Flow

Participant milestones

Participant milestones
Measure	L-glutamine Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	Placebo Patients will be randomized to receive Placebo. Placebo (100% maltodextrin): 0.3 g/kg of placebo will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
Overall Study STARTED	152	78
Overall Study COMPLETED	97	59
Overall Study NOT COMPLETED	55	19

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	L-glutamine n=152 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	Placebo n=78 Participants Patients will be randomized to receive Placebo. Placebo: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.	Total n=230 Participants Total of all reporting groups
Age, Categorical <=18 years	75 Participants n=99 Participants	43 Participants n=107 Participants	118 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	77 Participants n=99 Participants	35 Participants n=107 Participants	112 Participants n=206 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Continuous	22.4 years STANDARD_DEVIATION 12.32 • n=99 Participants	21.4 years STANDARD_DEVIATION 12.42 • n=107 Participants	22.0 years STANDARD_DEVIATION 12.33 • n=206 Participants
Sex: Female, Male Female	79 Participants n=99 Participants	45 Participants n=107 Participants	124 Participants n=206 Participants
Sex: Female, Male Male	73 Participants n=99 Participants	33 Participants n=107 Participants	106 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	144 Participants n=99 Participants	73 Participants n=107 Participants	217 Participants n=206 Participants
Race (NIH/OMB) White	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=99 Participants	5 Participants n=107 Participants	13 Participants n=206 Participants
Diagnosis Sickle Cell Anemia	136 Participants n=99 Participants	71 Participants n=107 Participants	207 Participants n=206 Participants
Diagnosis Sickle Beta plus Thalassemia	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
Diagnosis Sickle Beta zero Thalassemia	14 Participants n=99 Participants	7 Participants n=107 Participants	21 Participants n=206 Participants

PRIMARY outcome

Timeframe: 48 weeks

Population: Intent-to-Treat Population - Included all patients who were randomized and dispensed study medication.

Outcome measures

Outcome measures
Measure	L-glutamine n=152 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 Participants Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
The Number of Occurrences of Sickle Cell Crises	3 Number of crises Interval 0.0 to 15.0	4 Number of crises Interval 0.0 to 15.0

SECONDARY outcome

Timeframe: 48 weeks

Population: Intent-to-Treat Population - Included all patients who were randomized and dispensed study medication.

The number of hospitalizations that occur from Week 0 to Week 48, will be used to evaluate the efficacy of oral L-glutamine as a treatment for sickle cell anemia and beta-0 thalassemia.

Outcome measures

Outcome measures
Measure	L-glutamine n=152 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 Participants Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
The Number of Hospitalizations for Sickle Cell Pain	2 Number of hospitalizations Interval 0.0 to 14.0	3 Number of hospitalizations Interval 0.0 to 13.0

SECONDARY outcome

Timeframe: 48 weeks

Population: Intent-to-Treat Population - Included all patients who were randomized and dispensed study medication.

The number of emergency room visits or medical facility visits that occur from Week 0 to Week 48, will be used to evaluate the efficacy of oral L-glutamine as a treatment for sickle cell anemia and beta-0 thalassemia.

Outcome measures

Outcome measures
Measure	L-glutamine n=152 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 Participants Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
The Number of Emergency Room/Medical Facility Visits for Sickle Cell Pain	1 Number of ER visits Interval 0.0 to 12.0	1 Number of ER visits Interval 0.0 to 15.0

SECONDARY outcome

Timeframe: Baseline, Week 4, 24 and 48

Population: Safety population - The safety population included all patients who received at least 1 dose of study medication.

To assess the effect of oral L-glutamine on hematological parameters (hemoglobin), Change from Baseline will be reported at Weeks 4, 24 and 48.

Outcome measures

Outcome measures
Measure	L-glutamine n=151 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 Participants Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
The Effect of Oral -L-glutamine on Hematological Parameters Hemoglobin at Baseline	8.82 g/dL Standard Deviation 1.43	8.71 g/dL Standard Deviation 1.17
The Effect of Oral -L-glutamine on Hematological Parameters Change in Hemoglobin at week 4	0.04 g/dL Standard Deviation 0.84	0.23 g/dL Standard Deviation 0.71
The Effect of Oral -L-glutamine on Hematological Parameters Change in Hemoglobin at Week 24	-0.17 g/dL Standard Deviation 1.01	-0.12 g/dL Standard Deviation 1.24
The Effect of Oral -L-glutamine on Hematological Parameters Change in Hemoglobin at Week 48	-0.12 g/dL Standard Deviation 0.95	-0.12 g/dL Standard Deviation 0.96

SECONDARY outcome

Timeframe: Baseline, Week 4, 24, and 48

Population: Safety Population which includes all patients that took at least one dose of study medication.

To assess the effect of oral L-glutamine on Vital signs (systolic and diastolic blood pressure). Change from Baseline will be reported at Weeks 4, 24, and 48.

Outcome measures

Outcome measures
Measure	L-glutamine n=151 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 Participants Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
The Effect of Oral L-glutamine on Vital Signs Systolic blood pressure at Baseline	111.3 mm Hg Standard Deviation 11.20	114.6 mm Hg Standard Deviation 14.16
The Effect of Oral L-glutamine on Vital Signs Change Systolic blood pressure at Week 4	0.5 mm Hg Standard Deviation 11.19	-0.2 mm Hg Standard Deviation 10.68
The Effect of Oral L-glutamine on Vital Signs Change in Systolic blood pressure at Week 24	1.1 mm Hg Standard Deviation 10.78	0.5 mm Hg Standard Deviation 14.23
The Effect of Oral L-glutamine on Vital Signs Change in Systolic blood pressure at Week 48	2.2 mm Hg Standard Deviation 10.78	2.6 mm Hg Standard Deviation 15.70
The Effect of Oral L-glutamine on Vital Signs Diastolic blood pressure at Baseline	64.8 mm Hg Standard Deviation 8.61	66.2 mm Hg Standard Deviation 9.75
The Effect of Oral L-glutamine on Vital Signs Change in Diastolic blood pressure at Week 4	-0.7 mm Hg Standard Deviation 9.08	0.3 mm Hg Standard Deviation 10.29
The Effect of Oral L-glutamine on Vital Signs Change in Diastolic blood pressure at Week 24	-0.7 mm Hg Standard Deviation 8.40	0.6 mm Hg Standard Deviation 12.44
The Effect of Oral L-glutamine on Vital Signs Change in Diastolic blood pressure at Week 48	0.4 mm Hg Standard Deviation 8.71	2.0 mm Hg Standard Deviation 9.96

SECONDARY outcome

Timeframe: Baseline, Week 4, 24 and 48

Population: Safety population - The safety population included all patients who received at least 1 dose of study medication.

To assess the effect of oral L-glutamine on hematological parameters (hematocrit), Change from Baseline will be reported at Weeks 4, 24 and 48.

Outcome measures

Outcome measures
Measure	L-glutamine n=151 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 Participants Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
The Effect of Oral L-glutamine on Hematological Parameters Hematocrit at Baseline	27.67 % of red blood cells Standard Deviation 4.40	27.53 % of red blood cells Standard Deviation 3.61
The Effect of Oral L-glutamine on Hematological Parameters Change in Hematocrit at Week 4	0.16 % of red blood cells Standard Deviation 2.77	0.75 % of red blood cells Standard Deviation 2.52
The Effect of Oral L-glutamine on Hematological Parameters Change in Hematocrit Week 24	-0.26 % of red blood cells Standard Deviation 3.42	-0.15 % of red blood cells Standard Deviation 4.13
The Effect of Oral L-glutamine on Hematological Parameters Change in Hematocrit at Week 48	0.16 % of red blood cells Standard Deviation 3.27	0.11 % of red blood cells Standard Deviation 3.19

SECONDARY outcome

Timeframe: Baseline, Week 4, 24 and 48

Population: Safety population - The safety population included all patients who received at least 1 dose of study medication.

To assess the effect of oral L-glutamine on hematological parameters (reticulocyte count), Change from Baseline will be reported at Weeks 4, 24 and 48.

Outcome measures

Outcome measures
Measure	L-glutamine n=151 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 Participants Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
The Effect of Oral L-glutamine on Hematological Parameters Change in Reticulocyte (Abs) at Week 4	-9.28 1000 cells/uL Standard Deviation 104.88	-23.09 1000 cells/uL Standard Deviation 160.41
The Effect of Oral L-glutamine on Hematological Parameters Change in Reticulocyte (Abs) at Week 24	7.94 1000 cells/uL Standard Deviation 111.85	-1.93 1000 cells/uL Standard Deviation 137.65
The Effect of Oral L-glutamine on Hematological Parameters Change in Reticulocyte (Abs) at Week 48	50.89 1000 cells/uL Standard Deviation 112.93	26.27 1000 cells/uL Standard Deviation 140.65
The Effect of Oral L-glutamine on Hematological Parameters Reticulocyte (Abs)	283.62 1000 cells/uL Standard Deviation 129.49	295.03 1000 cells/uL Standard Deviation 140.10

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 24 and Week 48

Population: Safety Population which includes all patients that took at least one dose of study medication.

To assess the effect of oral L-glutamine on Vital signs (pulse rate). Change from Baseline will be reported at Weeks 4, 24, and 48.

Outcome measures

Outcome measures
Measure	L-glutamine n=151 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 Participants Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
The Effect of Oral L-glutamine on Vital Signs Pulse Rate (bpm) at Baseline	85.6 bpm Standard Deviation 13.15	88.5 bpm Standard Deviation 14.07
The Effect of Oral L-glutamine on Vital Signs Change in Pulse Rate (bpm) at Week 4	-0.1 bpm Standard Deviation 12.07	-0.4 bpm Standard Deviation 14.96
The Effect of Oral L-glutamine on Vital Signs Change in Pulse Rate (bpm) at Week 24	3.0 bpm Standard Deviation 14.58	-1.5 bpm Standard Deviation 15.05
The Effect of Oral L-glutamine on Vital Signs Change in Pulse Rate (bpm) at 48	1.1 bpm Standard Deviation 14.74	0.2 bpm Standard Deviation 15.33

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 24 and Week 48

Population: Safety Population which includes all patients that took at least one dose of study medication.

To assess the effect of oral L-glutamine on Vital signs (temperature). Change from Baseline will be reported at Weeks 4, 24, and 48.

Outcome measures

Outcome measures
Measure	L-glutamine n=151 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 Participants Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
Effect of Oral L-glutamine on Vital Signs Temperature at Baseline	36.85 degree C Standard Deviation 0.387	36.83 degree C Standard Deviation 0.403
Effect of Oral L-glutamine on Vital Signs Change in Temperature at Week 4	-0.06 degree C Standard Deviation 0.436	-0.02 degree C Standard Deviation 0.540
Effect of Oral L-glutamine on Vital Signs Change in Temperature at Week 24	-0.05 degree C Standard Deviation 0.469	0.03 degree C Standard Deviation 0.510
Effect of Oral L-glutamine on Vital Signs Change in Temperature at Week 48	-0.09 degree C Standard Deviation 0.442	0.05 degree C Standard Deviation 0.521

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 24 and Week 48

Population: Safety Population which includes all patients that took at least one dose of study medication.

To assess the effect of oral L-glutamine on Vital signs (respiration). Change from Baseline will be reported at Weeks 4, 24, and 48.

Outcome measures

Outcome measures
Measure	L-glutamine n=151 Participants Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 Participants Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
The Effect of Oral L-glutamine on Vital Signs Respiration at Baseline	18.9 breaths/min Standard Deviation 3.0	19.1 breaths/min Standard Deviation 2.34
The Effect of Oral L-glutamine on Vital Signs Change in Respiration at Week 4	-0.2 breaths/min Standard Deviation 3.01	-0.2 breaths/min Standard Deviation 2.55
The Effect of Oral L-glutamine on Vital Signs Change in Respiration at Week 24	-0.7 breaths/min Standard Deviation 3.03	-0.6 breaths/min Standard Deviation 3.36
The Effect of Oral L-glutamine on Vital Signs Change in Respiration at Week 48	-0.7 breaths/min Standard Deviation 3.25	-0.6 breaths/min Standard Deviation 2.94

Adverse Events

L-glutamine

Serious events: 118 serious events

Other events: 148 other events

Deaths: 0 deaths

100% Maltodextrin

Serious events: 68 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Yutaka Niihara, MD, MPH

Emmaus Medical, Inc

Phone: 310-214-0065

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI agrees that any INFORMATION submitted to it by EMMAUS shall be maintained in secrecy for a period of seven (7) years from each disclosure of INFORMATION. PI will use the up most due diligence to prevent disclosure by it except to its employees, agents, and contractors necessary for evaluation, all of whom shall be bound by similar written obligations of confidentiality, and who agree not to use the INFORMATION for any purpose other than for evaluation purposes.
Publication restrictions are in place

Restriction type: OTHER

Measure	L-glutamine n=151 participants at risk Patients will be randomized to receive investigational product, L-Glutamine. L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.	100% Maltodextrin n=78 participants at risk Patients will be randomized to receive Placebo. 100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.
Blood and lymphatic system disorders Anaemia	4.6% 7/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	7.7% 6/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Cardiac disorders Tachycardia	5.3% 8/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	5.1% 4/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Congenital, familial and genetic disorders Sickle cell anaemia with crisis	81.5% 123/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	91.0% 71/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Eye disorders Ocular icterus	9.9% 15/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	11.5% 9/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Gastrointestinal disorders Constipation	25.2% 38/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	24.4% 19/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Gastrointestinal disorders Nausea	22.5% 34/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	16.7% 13/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Gastrointestinal disorders Vomiting	14.6% 22/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	12.8% 10/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain	11.9% 18/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	12.8% 10/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Blood and lymphatic system disorders Acute chest syndrome	11.9% 18/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	26.9% 21/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Blood and lymphatic system disorders Leukocytosis	6.0% 9/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	7.7% 6/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain upper	10.6% 16/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	7.7% 6/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Gastrointestinal disorders Diarrhoea	7.9% 12/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.4% 5/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
General disorders Pyrexia	21.9% 33/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	37.2% 29/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
General disorders Chest pain	13.9% 21/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	9.0% 7/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
General disorders Fatigue	6.0% 9/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	1.3% 1/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
General disorders Oedema peripheral	5.3% 8/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	10.3% 8/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Upper respiratory tract infection	17.9% 27/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	23.1% 18/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	6.6% 10/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	7.7% 6/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Urinary tract infection	6.6% 10/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	3.8% 3/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Pneumonia	6.0% 9/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	17.9% 14/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Bronchitis	3.3% 5/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	5.1% 4/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Infections and infestations Gastroenteritis	3.3% 5/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	5.1% 4/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Metabolism and nutrition disorders Hypokalaemia	4.0% 6/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.4% 5/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Investigations Hypomanesaemia	4.0% 6/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	5.1% 4/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Metabolism and nutrition disorders Hyperkalaemia	3.3% 5/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	5.1% 4/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	15.9% 24/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	7.7% 6/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	13.2% 20/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.4% 5/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	12.6% 19/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	12.8% 10/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Nervous system disorders Headache	21.2% 32/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	17.9% 14/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Nervous system disorders Dizziness	5.3% 8/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	5.1% 4/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	17.2% 26/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	17.9% 14/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.3% 11/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	6.4% 5/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharnyngeal pain	7.3% 11/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	14.1% 11/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.3% 8/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	9.0% 7/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.3% 5/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	5.1% 4/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.6% 4/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	7.7% 6/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	9.3% 14/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	14.1% 11/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Rash	2.0% 3/151 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.	17.9% 14/78 • Adverse events data were collected throughout the course of the study (53 weeks or about 1 year). The Safety population will include all patients who received at least one dose of study medication.