Trial Outcomes & Findings for Low Dose Naltrexone for Glioma Patients (NCT NCT01303835)

Last Updated: 2015-07-17

Results Overview

The difference in QoL scores between the 3rd QoL measurement (approximately 16 weeks from initial assessment) and the initial baseline assessment are reported. QoL instruments included are listed below. Higher scores indicate more favorable outcomes unless otherwise indicated. * Functional Assessment of Cancer Therapy-Brain (FACT-Br) measures general QoL reflecting symptoms associated with brain malignancies (range 0-132) * Functional Assessment of Chronic Illness Therapy (FACIT-F) measures level of fatigue during patients' usual daily activities (range 0-52) * Epworth Sleepiness Scale measures level of daytime sleepiness. Note that higher scores indicate a greater level of sleepiness (range 0-24) * Medical Outcomes Survey (MOS) measures QoL including physical, mental and general health via 8 domains (range 0-100 for each domain) * Zung Self-Rating Depression Scale quantifies the depressed status of a patient. Lower scores indicate more favorable outcome (range 20-80) A difference

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

110 participants

Primary outcome timeframe

Baseline and 16 weeks

Results posted on

2015-07-17

Participant Flow

Patients were randomized to either low dose naltrexone (LDN) or placebo and were followed for 24 weeks. A patient is defined as completing the study if they completed the Quality of Life (QoL) assessments at 24 weeks.

Participant milestones

Participant milestones
Measure	Naltrexone Randomized patients received 4.5 mg naltrexone to be taken every night before bed.	Placebo Randomized patients received placebo to be taken every night before bed.
Overall Study STARTED	54	56
Overall Study COMPLETED	35	31
Overall Study NOT COMPLETED	19	25

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Low Dose Naltrexone for Glioma Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Naltrexone n=54 Participants Randomized patients received 4.5 mg naltrexone to be taken every night before bed.	Placebo n=56 Participants Randomized patients received placebo to be taken every night before bed.	Total n=110 Participants Total of all reporting groups
Age, Continuous	55.6 years STANDARD_DEVIATION 11.0 • n=99 Participants	56.7 years STANDARD_DEVIATION 11.3 • n=107 Participants	56.2 years STANDARD_DEVIATION 11.1 • n=206 Participants
Sex: Female, Male Female	23 Participants n=99 Participants	25 Participants n=107 Participants	48 Participants n=206 Participants
Sex: Female, Male Male	31 Participants n=99 Participants	31 Participants n=107 Participants	62 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline and 16 weeks

Population: This analysis only includes those patients who completed both the initial QOL assessments and the 16 week QoL assessments, and thus number of participants may not match those reported in the participant flow module, which reports number of participants completing the trial at 24 weeks.

Outcome measures

Outcome measures
Measure	Low Dose Naltrexone (LDN) n=37 Participants Randomized patients received 4.5 mg naltrexone to be taken every night before bed.	Placebo n=39 Participants Randomized patients received placebo to be taken every night before bed.
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline FACT-Brain Trial Outcome Index (TOI)	-3.73 Scores on a Scale Standard Deviation 22.85	-6.06 Scores on a Scale Standard Deviation 21.72
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline FACIT-Fatigue	-4.22 Scores on a Scale Standard Deviation 11.07	-4.1 Scores on a Scale Standard Deviation 13.41
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline Epworth Sleepiness Scale	3.47 Scores on a Scale Standard Deviation 4.37	0.81 Scores on a Scale Standard Deviation 3.45
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline MOS - Physical Functioning	-5.54 Scores on a Scale Standard Deviation 34.41	-3.42 Scores on a Scale Standard Deviation 29.75
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline MOS - Role Limitations due to Physical Health	0 Scores on a Scale Standard Deviation 51.71	20.39 Scores on a Scale Standard Deviation 41.86
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline MOS - Role Limitations due to Emotional Issues	2.69 Scores on a Scale Standard Deviation 49.31	12.3 Scores on a Scale Standard Deviation 56.11
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline MOS - Energy/Fatigue	-6.22 Scores on a Scale Standard Deviation 29.8	-4.61 Scores on a Scale Standard Deviation 29.76
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline MOS - Emotional Well Being	3.5 Scores on a Scale Standard Deviation 21.4	-1.89 Scores on a Scale Standard Deviation 15.64
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline MOS - Social Functioning	1.34 Scores on a Scale Standard Deviation 32.38	7.87 Scores on a Scale Standard Deviation 41.57
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline MOS - Pain	10.41 Scores on a Scale Standard Deviation 27.12	2.39 Scores on a Scale Standard Deviation 24.92
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline MOS - General Health	-13.38 Scores on a Scale Standard Deviation 17.8	-12.11 Scores on a Scale Standard Deviation 19.82
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline Zung Depression Scale	0.86 Scores on a Scale Standard Deviation 11.15	3.54 Scores on a Scale Standard Deviation 8.48

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: This analysis only includes those patients who completed both the initial 6MWT assessments and the 16 week assessments, and thus number of participants may not match those reported in the participant flow module, which reports number of participants completing the trial at 24 weeks.

Patients completed the 6-minute walk test (6MWT) at each QoL measurement assessment. The 6 minute walk test is a measure of functional capacity in which the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes is measured. The mean difference in distance traveled (in meters) between the 3rd QoL measurement (approximately 16 weeks from initial assessment) and the initial baseline assessment are reported. A difference greater than 0 indicates an increase in distance traveled, while a difference less than 0 indicates a decrease.

Outcome measures

Outcome measures
Measure	Low Dose Naltrexone (LDN) n=37 Participants Randomized patients received 4.5 mg naltrexone to be taken every night before bed.	Placebo n=36 Participants Randomized patients received placebo to be taken every night before bed.
Effects of Low-dose Naltrexone Versus Placebo on Change in Functional Capacity From Baseline	13.43 Meters Standard Deviation 113.7	-6.42 Meters Standard Deviation 136.73

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: This analysis only includes those patients who completed both the initial CNS Vital Signs assessments and the 16 week assessments, and thus number of participants may not match those reported in the participant flow module, which reports number of participants completing the trial at 24 weeks.

Patients completed neurocognitive testing at each QoL measurement assessment. Neurocognitive function was measured via a computerized neurocognitive test battery called CNS Vital Signs. The battery consists of 7 tests that assess verbal and visual memory, finger tapping, symbol digit coding, the Stroop Test, a test of shifting attention, and continuous performance. The battery provides scores over 9 domains with higher scores indicating better performance. Scores were normalized to a standard score mean of 100 and standard deviation of 15 using a normative sample. The mean difference in score in each domain between the 3rd QoL measurement (approximately 16 weeks from initial assessment) and the initial baseline assessment are reported. A difference greater than 0 indicates an increase in mean score, while a difference less than 0 indicates a decrease in mean score.

Outcome measures

Outcome measures
Measure	Low Dose Naltrexone (LDN) n=21 Participants Randomized patients received 4.5 mg naltrexone to be taken every night before bed.	Placebo n=25 Participants Randomized patients received placebo to be taken every night before bed.
Effects of Low-dose Naltrexone Versus Placebo on Change in Neurocognitive Function From Baseline Memory	-5.38 Scores on a Scale Standard Deviation 24.03	-0.24 Scores on a Scale Standard Deviation 17.63
Effects of Low-dose Naltrexone Versus Placebo on Change in Neurocognitive Function From Baseline Processing Speed	-0.71 Scores on a Scale Standard Deviation 24.72	7.32 Scores on a Scale Standard Deviation 19.17
Effects of Low-dose Naltrexone Versus Placebo on Change in Neurocognitive Function From Baseline Reaction Time	-7.24 Scores on a Scale Standard Deviation 29.61	-8.64 Scores on a Scale Standard Deviation 17.03
Effects of Low-dose Naltrexone Versus Placebo on Change in Neurocognitive Function From Baseline Verbal Memory	-0.1 Scores on a Scale Standard Deviation 28.22	2 Scores on a Scale Standard Deviation 17.29
Effects of Low-dose Naltrexone Versus Placebo on Change in Neurocognitive Function From Baseline Visual Memory	-8.38 Scores on a Scale Standard Deviation 19.05	-2.24 Scores on a Scale Standard Deviation 19.32
Effects of Low-dose Naltrexone Versus Placebo on Change in Neurocognitive Function From Baseline Cognitive Flexibility	3.62 Scores on a Scale Standard Deviation 23.14	7.44 Scores on a Scale Standard Deviation 22.12
Effects of Low-dose Naltrexone Versus Placebo on Change in Neurocognitive Function From Baseline Complex Attention	7.33 Scores on a Scale Standard Deviation 32.07	6.24 Scores on a Scale Standard Deviation 18.84
Effects of Low-dose Naltrexone Versus Placebo on Change in Neurocognitive Function From Baseline Psychomotor Speed	-0.76 Scores on a Scale Standard Deviation 13	4.72 Scores on a Scale Standard Deviation 11.6
Effects of Low-dose Naltrexone Versus Placebo on Change in Neurocognitive Function From Baseline Executive Functioning	3.9 Scores on a Scale Standard Deviation 23.17	7.56 Scores on a Scale Standard Deviation 22.87

Adverse Events

Naltrexone

Serious events: 12 serious events

Other events: 51 other events

Deaths: 0 deaths

Placebo

Serious events: 17 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Katherine B. Peters, MD, PhD

Duke University Medical Center, The Preston Robert Tisch Brain Tumor Center

Phone: (919) 684-6173

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Naltrexone n=54 participants at risk Randomized patients received 4.5 mg low dose naltrexone (LDN) to be taken every night before bed.	Placebo n=56 participants at risk Randomized patients received placebo to be taken every night before bed.
Blood and lymphatic system disorders Anemia	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Cardiac disorders Atrial fibrillation	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Cardiac disorders Sinus tachycardia	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Gastrointestinal disorders Dysphagia	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Gastrointestinal disorders Nausea	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	0.00% 0/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Gastrointestinal disorders Pancreatitis	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Gastrointestinal disorders Vomiting	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	0.00% 0/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
General disorders Edema face	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
General disorders Edema limbs	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
General disorders Fatigue	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	0.00% 0/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
General disorders Fever	3.7% 2/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Infections and infestations Encephalitis infection	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Infections and infestations Lung infection	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	5.4% 3/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Infections and infestations Mucosal infection	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Infections and infestations Rash pustular	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Infections and infestations Sepsis	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Infections and infestations Urinary tract infection	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	0.00% 0/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Investigations Neutrophil count decreased	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	3.6% 2/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Investigations Platelet count decreased	3.7% 2/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	3.6% 2/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Investigations White blood cell decreased	3.7% 2/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	3.6% 2/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Metabolism and nutrition disorders Dehydration	5.6% 3/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	0.00% 0/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Metabolism and nutrition disorders Hyponatremia	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	3.6% 2/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	0.00% 0/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Nervous system disorders Dysphasia	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Nervous system disorders Edema cerebral	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	0.00% 0/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Nervous system disorders Encephalopathy	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	3.6% 2/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Nervous system disorders Headache	5.6% 3/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Nervous system disorders Pyramidal tract syndrome	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Nervous system disorders Seizure	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	3.6% 2/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Nervous system disorders Somnolence	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Psychiatric disorders Confusion	3.7% 2/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	0.00% 0/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	3.6% 2/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	3.6% 2/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Respiratory, thoracic and mediastinal disorders Pulmonary edema	1.9% 1/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	0.00% 0/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Vascular disorders Hypotension	0.00% 0/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	1.8% 1/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0
Vascular disorders Thromboembolic event	3.7% 2/54 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0	12.5% 7/56 • 24 weeks The adverse events were gathered in Common Terminology Criteria for Adverse Events v.4.0