Phenylketonuria Clinical Trial
— PKUOfficial title:
Phase 2 Study of Glycomacropeptide vs. Amino Acid Diet for the Management of PKU
Verified date | July 2018 |
Source | University of Wisconsin, Madison |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
For individuals with Phenylketonuria (PKU), the investigators hypothesize that glycomacropeptide will provide an acceptable form of low-phenylalanine dietary protein that will improve dietary compliance, blood phenylalanine levels, cognitive function, and ultimately quality of life compared with the usual amino acid based diet. The study is funded by the Food and Drug Administration (FDA) Office of Orphan Products Development Grants Program, R01 FD003711.
Status | Completed |
Enrollment | 32 |
Est. completion date | May 2016 |
Est. primary completion date | November 2015 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 12 Years to 45 Years |
Eligibility |
Inclusion Criteria: - Identified PKU by newborn screening; started diet treatment before 1 mo age - Diagnosis of classical or variant PKU with documented phenylalanine level of greater than 600 umol/L at 7-10d of age - Follows or willing to follow PKU diet and consume amino acid medical formula providing more than 50% of protein needs - Acceptance of glycomacropeptide foods determined prior to enrollment Exclusion Criteria: - Females who are pregnant or planning pregnancy - Individuals with mental deficits due to untreated or poorly controlled PKU - Individuals with any health condition deemed to interfere with participation |
Country | Name | City | State |
---|---|---|---|
United States | Children's Hospital of Boston | Boston | Massachusetts |
United States | University of Wisconsin-Madison | Madison | Wisconsin |
Lead Sponsor | Collaborator |
---|---|
University of Wisconsin, Madison | Boston Children’s Hospital |
United States,
Laclair CE, Ney DM, MacLeod EL, Etzel MR. Purification and use of glycomacropeptide for nutritional management of phenylketonuria. J Food Sci. 2009 May-Jul;74(4):E199-206. doi: 10.1111/j.1750-3841.2009.01134.x. — View Citation
MacLeod EL, Clayton MK, van Calcar SC, Ney DM. Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria. Mol Genet Metab. 2010 Aug;100(4):303-8. doi: 10.1016/j.ymgme.2010.04.003. Epub 2010 Apr 14. — View Citation
Ney DM, Gleason ST, van Calcar SC, MacLeod EL, Nelson KL, Etzel MR, Rice GM, Wolff JA. Nutritional management of PKU with glycomacropeptide from cheese whey. J Inherit Metab Dis. 2009 Feb;32(1):32-9. doi: 10.1007/s10545-008-0952-4. Epub 2008 Oct 29. Review. — View Citation
Ney DM, Hull AK, van Calcar SC, Liu X, Etzel MR. Dietary glycomacropeptide supports growth and reduces the concentrations of phenylalanine in plasma and brain in a murine model of phenylketonuria. J Nutr. 2008 Feb;138(2):316-22. — View Citation
Ney DM, Murali SG, Stroup BM, Nair N, Sawin EA, Rohr F, Levy HL. Metabolomic changes demonstrate reduced bioavailability of tyrosine and altered metabolism of tryptophan via the kynurenine pathway with ingestion of medical foods in phenylketonuria. Mol Ge — View Citation
Ney DM, Stroup BM, Clayton MK, Murali SG, Rice GM, Rohr F, Levy HL. Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial. Am J Clin Nutr. 2016 Aug;104(2):334-45. doi: 10.3945/ajcn.116.135293. Epub 2016 — View Citation
Stroup BM, Hansen KE, Krueger D, Binkley N, Ney DM. Sex differences in body composition and bone mineral density in phenylketonuria: A cross-sectional study. Mol Genet Metab Rep. 2018 Feb 3;15:30-35. doi: 10.1016/j.ymgmr.2018.01.004. eCollection 2018 Jun. — View Citation
Stroup BM, Held PK, Williams P, Clayton MK, Murali SG, Rice GM, Ney DM. Clinical relevance of the discrepancy in phenylalanine concentrations analyzed using tandem mass spectrometry compared with ion-exchange chromatography in phenylketonuria. Mol Genet M — View Citation
Stroup BM, Murali SG, Nair N, Sawin EA, Rohr F, Levy HL, Ney DM. Dietary amino acid intakes associated with a low-phenylalanine diet combined with amino acid medical foods and glycomacropeptide medical foods and neuropsychological outcomes in subjects wit — View Citation
Stroup BM, Nair N, Murali SG, Broniowska K, Rohr F, Levy HL, Ney DM. Metabolomic Markers of Essential Fatty Acids, Carnitine, and Cholesterol Metabolism in Adults and Adolescents with Phenylketonuria. J Nutr. 2018 Feb 1;148(2):194-201. doi: 10.1093/jn/nxx — View Citation
Stroup BM, Ney DM, Murali SG, Rohr F, Gleason ST, van Calcar SC, Levy HL. Metabolomic Insights into the Nutritional Status of Adults and Adolescents with Phenylketonuria Consuming a Low-Phenylalanine Diet in Combination with Amino Acid and Glycomacropepti — View Citation
Stroup BM, Sawin EA, Murali SG, Binkley N, Hansen KE, Ney DM. Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonur — View Citation
van Calcar SC, MacLeod EL, Gleason ST, Etzel MR, Clayton MK, Wolff JA, Ney DM. Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids. Am J Clin Nutr. 2009 Apr;89(4):1068-77. doi: 10.3945/ajcn.2008.27280. Epub 2009 Feb 25. Erratum in: Am J Clin Nutr. 2010 Apr;91(4):1072. — View Citation
* Note: There are 13 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Bone Mineral Density Determined by Dual-energy X-ray Absorptiometry (DXA) Scan | Subjects 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. | once during first 3 week dietary treatment | |
Primary | Change in the Plasma Phenylalanine Concentration of PKU Subjects Fed the Glycomacropeptide Diet Compared With the Change When Fed the Amino Acid Diet | 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. | baseline to day 22 on each diet | |
Secondary | Dietary Compliance | Compliance 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. | 3 week dietary treatment | |
Secondary | Executive Function Assessed by BRIEF | Completion 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. | day 22 of each dietary treatment | |
Secondary | Vitamin D (25-OH) Plasma Concentration at Day 22 | Vitamin D was measured as a measure of the capacity for calcium absorption. Higher levels of plasma vitamin D are consistent with higher calcium absorption. | day 22 of each dietary treatment | |
Secondary | Comparison of Phe Concentrations in Plasma With Concentrations in Dried Blood Spots | 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. | 4 times total, 2 per treatment | |
Secondary | Bone-specific Alkaline Phosphatase (BSAP) Plasma Concentration at Day 22 | Plasma concentration of BSAP was determined as a measure of bone turnover. | day 22 of each dietary treatment | |
Secondary | N-terminal Telopeptide (NTX) Plasma Concentration at Day 22 | Plasma concentration of NTX was determined as a measure of bone resorption; higher levels indicate greater bone breakdown | day 22 of each dietary treatment |
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