Trial Outcomes & Findings for Phase 2 Study of Glycomacropeptide Versus Amino Acid Diet for Management of Phenylketonuria (NCT NCT01428258)
NCT ID: NCT01428258
Last Updated: 2018-08-24
Results Overview
Plasma will be collected at each base week and after 3 weeks on each of the dietary treatments, glycomacropeptide and amino acid, following an overnight fast. Plasma phenylalanine concentration (along with the complete profile of free amino acids) will be determined with an amino acid analyzer in the Wisconsin State Lab of Hygiene. Statistical analysis to determine the significance of the change in plasma phe concentration when comparing the 2 diets will consist of ANCOVA with covariates for baseline Phe and dietary Phe intake. The change in plasma Phe concentration from day 22 (final) to day 1 (baseline) was determined after adjusting for baseline Phe level and dietary Phe intake.
COMPLETED
NA
32 participants
baseline to day 22 on each diet
2018-08-24
Participant Flow
Participant milestones
| Measure |
GMP Diet-AA Diet
In this randomized crossover study, half of subjects will be assigned to an arm that consists of the the GMP diet followed by the AA diet referred to as the Glycomacropeptide (GMP) diet given first intervention.
Glycomacropeptide (GMP) diet given first: The intervention compares a new low-phenylalanine (phe) dietary therapy for PKU, a diet containing foods and beverages made from GMP using Glytactin provided by Cambrooke Foods LLC, with the usual amino acid (AA) low-phe dietary therapy. PKU subjects in the GMP Diet-AA Diet Arm will follow the GMP diet that will replace all of the dietary protein equivalents provided by AA formula with foods and beverages made from GMP for 3 weeks followed by a 3 wk wash out period. They will then follow the usual AA diet for 3 weeks. Each dietary treatment period will maintain constant intake of total protein and phe and last for 3 weeks in subjects living at home.
|
AA Diet - GMP Diet
In this randomized crossover study, half of subjects will be assigned to an arm that consists of the AA diet followed by the GMP diet referred to as the Amino Acid (AA) Diet given first intervention.
Amino Acid (AA) Diet Given First: The intervention compares the usual amino acid (AA) low-phenylalanine (phe) dietary therapy with a new dietary therapy for PKU, a low-phe diet containing foods and beverages made from glycomacropeptide (GMP). PKU subjects in the AA Diet-GMP Diet Arm will follow their usual AA diet for 3 weeks followed by a 3 wk wash out period. They will then replace all of the protein equivalents provided in their diet by AA formula with foods and beverages made from GMP using Glytactin as provided by Cambrooke Foods, LLC. Each dietary treatment period will maintain constant intake of total protein and phe and last for 3 weeks in subjects living at home.
|
|---|---|---|
|
Intervention 1
STARTED
|
17
|
15
|
|
Intervention 1
COMPLETED
|
15
|
15
|
|
Intervention 1
NOT COMPLETED
|
2
|
0
|
|
Intervention 2
STARTED
|
15
|
15
|
|
Intervention 2
COMPLETED
|
15
|
15
|
|
Intervention 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
GMP Diet-AA Diet
In this randomized crossover study, half of subjects will be assigned to an arm that consists of the the GMP diet followed by the AA diet referred to as the Glycomacropeptide (GMP) diet given first intervention.
Glycomacropeptide (GMP) diet given first: The intervention compares a new low-phenylalanine (phe) dietary therapy for PKU, a diet containing foods and beverages made from GMP using Glytactin provided by Cambrooke Foods LLC, with the usual amino acid (AA) low-phe dietary therapy. PKU subjects in the GMP Diet-AA Diet Arm will follow the GMP diet that will replace all of the dietary protein equivalents provided by AA formula with foods and beverages made from GMP for 3 weeks followed by a 3 wk wash out period. They will then follow the usual AA diet for 3 weeks. Each dietary treatment period will maintain constant intake of total protein and phe and last for 3 weeks in subjects living at home.
|
AA Diet - GMP Diet
In this randomized crossover study, half of subjects will be assigned to an arm that consists of the AA diet followed by the GMP diet referred to as the Amino Acid (AA) Diet given first intervention.
Amino Acid (AA) Diet Given First: The intervention compares the usual amino acid (AA) low-phenylalanine (phe) dietary therapy with a new dietary therapy for PKU, a low-phe diet containing foods and beverages made from glycomacropeptide (GMP). PKU subjects in the AA Diet-GMP Diet Arm will follow their usual AA diet for 3 weeks followed by a 3 wk wash out period. They will then replace all of the protein equivalents provided in their diet by AA formula with foods and beverages made from GMP using Glytactin as provided by Cambrooke Foods, LLC. Each dietary treatment period will maintain constant intake of total protein and phe and last for 3 weeks in subjects living at home.
|
|---|---|---|
|
Intervention 1
Withdrawal by Subject
|
2
|
0
|
Baseline Characteristics
Phase 2 Study of Glycomacropeptide Versus Amino Acid Diet for Management of Phenylketonuria
Baseline characteristics by cohort
| Measure |
GMP Diet-AA Diet
n=17 Participants
In this randomized crossover study, half of subjects will be assigned to an arm that consists of the the GMP diet followed by the AA diet referred to as the Glycomacropeptide (GMP) diet given first intervention.
Glycomacropeptide (GMP) diet given first: The intervention compares a new low-phenylalanine (phe) dietary therapy for PKU, a diet containing foods and beverages made from GMP using Glytactin provided by Cambrooke Foods LLC, with the usual amino acid (AA) low-phe dietary therapy. PKU subjects in the GMP Diet-AA Diet Arm will follow the GMP diet that will replace all of the dietary protein equivalents provided by AA formula with foods and beverages made from GMP for 3 weeks followed by a 3 wk wash out period. They will then follow the usual AA diet for 3 weeks. Each dietary treatment period will maintain constant intake of total protein and phe and last for 3 weeks in subjects living at home.
|
AA Diet - GMP Diet
n=15 Participants
In this randomized crossover study, half of subjects will be assigned to an arm that consists of the AA diet followed by the GMP diet referred to as the Amino Acid (AA) Diet given first intervention.
Amino Acid (AA) Diet Given First: The intervention compares the usual amino acid (AA) low-phenylalanine (phe) dietary therapy with a new dietary therapy for PKU, a low-phe diet containing foods and beverages made from glycomacropeptide (GMP). PKU subjects in the AA Diet-GMP Diet Arm will follow their usual AA diet for 3 weeks followed by a 3 wk wash out period. They will then replace all of the protein equivalents provided in their diet by AA formula with foods and beverages made from GMP using Glytactin as provided by Cambrooke Foods, LLC. Each dietary treatment period will maintain constant intake of total protein and phe and last for 3 weeks in subjects living at home.
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
3 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
27 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
|
28 years
n=99 Participants
|
28 years
n=107 Participants
|
28 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
17 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: baseline to day 22 on each dietPlasma will be collected at each base week and after 3 weeks on each of the dietary treatments, glycomacropeptide and amino acid, following an overnight fast. Plasma phenylalanine concentration (along with the complete profile of free amino acids) will be determined with an amino acid analyzer in the Wisconsin State Lab of Hygiene. Statistical analysis to determine the significance of the change in plasma phe concentration when comparing the 2 diets will consist of ANCOVA with covariates for baseline Phe and dietary Phe intake. The change in plasma Phe concentration from day 22 (final) to day 1 (baseline) was determined after adjusting for baseline Phe level and dietary Phe intake.
Outcome measures
| Measure |
GMP Diet/GMP Medical Foods
n=30 Participants
All subjects received the Glycomacropeptide (GMP) diet either in the first or second period. The intervention consists of a low-Phe diet in combination with medical foods made from glycomacropeptide, a low-Phe whey protein.
|
AA Diet/AA Medical Foods
n=30 Participants
All subjects received the Amino Acid (AA) Diet in either the first or second period. The intervention consists of a low-Phe diet in combination with each subject's usual AA medical formula.
|
|---|---|---|
|
Change in the Plasma Phenylalanine Concentration of PKU Subjects Fed the Glycomacropeptide Diet Compared With the Change When Fed the Amino Acid Diet
|
62 micro moles per liter plasma
Standard Error 40
|
-85 micro moles per liter plasma
Standard Error 40
|
SECONDARY outcome
Timeframe: 3 week dietary treatmentCompliance with the glycomacropeptide and amino acid dietary treatments will be assessed by comparison of the intake of medical food in grams of protein from medical food per day based on subject completion of 3-day food records prior to the final study visit on day 22. Statistical analysis for a dietary treatment effect will consist of ANOVA.
Outcome measures
| Measure |
GMP Diet/GMP Medical Foods
n=30 Participants
All subjects received the Glycomacropeptide (GMP) diet either in the first or second period. The intervention consists of a low-Phe diet in combination with medical foods made from glycomacropeptide, a low-Phe whey protein.
|
AA Diet/AA Medical Foods
n=30 Participants
All subjects received the Amino Acid (AA) Diet in either the first or second period. The intervention consists of a low-Phe diet in combination with each subject's usual AA medical formula.
|
|---|---|---|
|
Dietary Compliance
|
0.74 g protein from MF/kg/day
Standard Error 0.04
|
0.76 g protein from MF/kg/day
Standard Error 0.05
|
SECONDARY outcome
Timeframe: day 22 of each dietary treatmentCompletion of a standardized test, the Behavior Rating Inventory of Executive Function (BRIEF), by each subject for the GMP diet and the AA diet. Values are T-scores which have a mean of 50 points and a SD of 10 points. A T score of \<50 is considered within the normative range. Data are analyzed with a paired t-test.
Outcome measures
| Measure |
GMP Diet/GMP Medical Foods
n=30 Participants
All subjects received the Glycomacropeptide (GMP) diet either in the first or second period. The intervention consists of a low-Phe diet in combination with medical foods made from glycomacropeptide, a low-Phe whey protein.
|
AA Diet/AA Medical Foods
n=30 Participants
All subjects received the Amino Acid (AA) Diet in either the first or second period. The intervention consists of a low-Phe diet in combination with each subject's usual AA medical formula.
|
|---|---|---|
|
Executive Function Assessed by BRIEF
|
49.0 T score
Standard Error 1.8
|
48.8 T score
Standard Error 2.1
|
SECONDARY outcome
Timeframe: day 22 of each dietary treatmentVitamin D was measured as a measure of the capacity for calcium absorption. Higher levels of plasma vitamin D are consistent with higher calcium absorption.
Outcome measures
| Measure |
GMP Diet/GMP Medical Foods
n=30 Participants
All subjects received the Glycomacropeptide (GMP) diet either in the first or second period. The intervention consists of a low-Phe diet in combination with medical foods made from glycomacropeptide, a low-Phe whey protein.
|
AA Diet/AA Medical Foods
n=30 Participants
All subjects received the Amino Acid (AA) Diet in either the first or second period. The intervention consists of a low-Phe diet in combination with each subject's usual AA medical formula.
|
|---|---|---|
|
Vitamin D (25-OH) Plasma Concentration at Day 22
|
33.8 ng per ml
Standard Error 1.70
|
33.6 ng per ml
Standard Error 1.52
|
SECONDARY outcome
Timeframe: 4 times total, 2 per treatmentPopulation: Analysis of sample pairs is required to determine the discrepancy in Phe levels with the 2 methods. Each subject should have had 4 sample pairs, 29 x 4 = 116, but we ended up with only 110 sample pairs. The explanation for the difference is that several subjects did not provide dried blood spots because research staff forgot to obtain them.
Concentrations of Phe in plasma and in dried blood spots collected simultaneously by subjects will be compared using 2 methodologies, regardless of intervention. At each of the 4 study visits (baseline and final for each dietary treatment): 1) venipuncture was used to collect blood and plasma was isolated and analyzed for Phe with ion exchange chromatography and 2) subjects were asked right after the venipuncture to spot their blood on filter paper for analysis of Phe with tandem mass spectroscopy (MS/MS). The discrepancy in Phe concentrations with these 2 methods was compared for each sample pair using Bland-Altman statistical analysis. Each subject should have had 4 sample pairs, 29 x 4 = 116, but we ended up with only 110 sample pairs, as explained below.
Outcome measures
| Measure |
GMP Diet/GMP Medical Foods
n=29 Participants
All subjects received the Glycomacropeptide (GMP) diet either in the first or second period. The intervention consists of a low-Phe diet in combination with medical foods made from glycomacropeptide, a low-Phe whey protein.
|
AA Diet/AA Medical Foods
n=29 Participants
All subjects received the Amino Acid (AA) Diet in either the first or second period. The intervention consists of a low-Phe diet in combination with each subject's usual AA medical formula.
|
|---|---|---|
|
Comparison of Phe Concentrations in Plasma With Concentrations in Dried Blood Spots
|
731 micro moles per liter
Standard Error 32
|
514 micro moles per liter
Standard Error 23
|
SECONDARY outcome
Timeframe: day 22 of each dietary treatmentPopulation: Samples were not obtained from 4 subjects due to a collection error by research staff. Thus the sample size is reduced from 30 to 26.
Plasma concentration of BSAP was determined as a measure of bone turnover.
Outcome measures
| Measure |
GMP Diet/GMP Medical Foods
n=26 Participants
All subjects received the Glycomacropeptide (GMP) diet either in the first or second period. The intervention consists of a low-Phe diet in combination with medical foods made from glycomacropeptide, a low-Phe whey protein.
|
AA Diet/AA Medical Foods
n=26 Participants
All subjects received the Amino Acid (AA) Diet in either the first or second period. The intervention consists of a low-Phe diet in combination with each subject's usual AA medical formula.
|
|---|---|---|
|
Bone-specific Alkaline Phosphatase (BSAP) Plasma Concentration at Day 22
|
17.0 micro gram per liter
Standard Error 2.1
|
17.0 micro gram per liter
Standard Error 2.2
|
SECONDARY outcome
Timeframe: day 22 of each dietary treatmentPopulation: Samples were not obtained from 3 subjects due to a collection error by research staff. Thus the sample size is reduced from 30 to 27.
Plasma concentration of NTX was determined as a measure of bone resorption; higher levels indicate greater bone breakdown
Outcome measures
| Measure |
GMP Diet/GMP Medical Foods
n=27 Participants
All subjects received the Glycomacropeptide (GMP) diet either in the first or second period. The intervention consists of a low-Phe diet in combination with medical foods made from glycomacropeptide, a low-Phe whey protein.
|
AA Diet/AA Medical Foods
n=27 Participants
All subjects received the Amino Acid (AA) Diet in either the first or second period. The intervention consists of a low-Phe diet in combination with each subject's usual AA medical formula.
|
|---|---|---|
|
N-terminal Telopeptide (NTX) Plasma Concentration at Day 22
|
17.5 nmol per liter bone collagen equivalents
Standard Error 0.66
|
17.1 nmol per liter bone collagen equivalents
Standard Error 0.65
|
OTHER_PRE_SPECIFIED outcome
Timeframe: once during first 3 week dietary treatmentSubjects will have a single DXA test to assess bone mineral density of the lumbar spine and total body during the first dietary treatment that they are randomly assigned to start with.
Outcome measures
Outcome data not reported
Adverse Events
GMP Diet/GMP Medical Foods
AA Diet/AA Medical Foods
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place