Nutritional and Neurotransmitter Changes in PKU Subjects on BH4

NCT00688844 | Completed Results

• 1 other identifier: IRB00007828
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 2

Brief Summary

HYPOTHESIS: The investigators hypothesize that KuvanTM therapy could influence nutritional and body composition parameters and neurotransmitter concentrations in pediatric and adult PKU subjects. SUMMARY: Though the investigators know that KuvanTM lowers blood Phe levels and improves tolerance for natural protein in at least half of the PKU (Phenylketonuria) patient population, investigators do not know the full effects this medicine will have on the patient's diet, or what impact the medicine or diet changes will have on the body composition or nutrient status of PKU patients. Since KuvanTM may also help the body produce neurotransmitters, investigators also want to find out if taking KuvanTM changes neurotransmitter levels in PKU patients, and if PKU patients who are benefitting from KuvanTM feel less stigmatized and have a better outlook on life as a result of the treatment. Therefore, the research study has several objectives. These are to investigate the impact KuvanTM therapy has on (1) body composition parameters of PKU patients: such as lean body mass, percent body fat, bone density, weight gain, and growth (2) dietary changes, and the effect of those changes, on intake of calories and essential nutrients (3) changes in blood biomarkers of certain nutrients (4) blood and urine neurotransmitter levels, since these changes could indicate improved neurological functioning, (5) and quality of life of PKU patients, who may feel less burdened due to the dietary freedom KuvanTM provides.

Conditions

Phenylketonuria

Keywords

PKU; Phenylketonuria; BH4; Kuvan; Tetrahydrobiopterin; Sapropterin Dihydrochloride; Nutrition; PHE; Phenylalanine; PAH; Phenylalanine hydroxylase; Neurotransmitters; Serotonin; Catecholamines; Diet; Body Fat; Bone Density

Outcome Measures

Primary Outcomes (7)

• Change From Baseline in BMI at 12 Months

  Change in Body mass index (BMI) from baseline of Kuvan study to 12 months post-baseline

  Baseline and 12 months

• Change From Baseline in Bone Mineral Density (BMD) at 12 Months

  Change in bone mineral density (BMD) from baseline of Kuvan study to 12 months post-baseline

  Baseline and 12 months

• Change From Baseline in Percent (%) Lean Mass at 12 Months

  % lean mass was measured via dual energy x-ray absorptiometry (DXA)

  Baseline and 12 months

• Change From Baseline in Percent (%) Fat Mass at 12 Months

  Percent fat mass measured via dual energy x-ray absorptiometry (DXA)

  Baseline and 12 months

• Change From Baseline in Plasma Phenylalanine at 12 Months

  Full amino acid panel, including phenylalanine, analyzed in fasting plasma samples.

  Baseline and 12 months

• Change From Baseline in Total Dietary Protein Intake at 12 Months

  Total dietary protein intake assessed through 3-day food records - calculated as average protein intake (grams/day) in the 3 days recorded

  Baseline and 12 months

• Change From Baseline in Phenylalanine Intake at 12 Months

  Total dietary phenylalanine assessed through 3-day food records - calculated as average phenylalanine intake (grams/day) in the 3 days recorded

  Baseline and 12 months

Other Outcomes (1)

• Change From Baseline in Serotonin at 12 Months

  Baseline and 12 months

Study Arms (1)

PKU subjects - baseline

Male and female subjects with PKU at baseline starting KuvanTM therapy.

Drug: KuvanTM Therapy

Interventions

KuvanTM Therapy DRUG

BH4 treatment was prescribed by each participant's medical provider, not an intervention that was assigned as part of the current study.

Also known as: BH4, Kuvan

PKU subjects - baseline

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Phenylketonuria (PKU) subjects ages 4 through adulthood who plan to start BH4 therapy but are not currently on BH4.

You may qualify if:

• Diagnosed with PKU
• ability to provide informed consent (or have legal guardian who can provide informed consent)
• at least 4 years of age
• planning on trying BH4 treatment

You may not qualify if:

• Pregnant
• unable to provide informed consent
• less than 4 years of age
• currently taking BH4

Sponsors & Collaborators

• Emory University: lead
• BioMarin Pharmaceutical: collaborator
• Atlanta Clinical and Translational Science Institute: collaborator

Study Sites (2)

Emory Hospital, CIN/ACTSI

Atlanta, Georgia, 30322, United States

Location

Emory University Genetics Clinic

Decatur, Georgia, 30033, United States

Location

Related Publications (1)

• Jani R, Coakley K, Douglas T, Singh R. Protein intake and physical activity are associated with body composition in individuals with phenylalanine hydroxylase deficiency. Mol Genet Metab. 2017 Jun;121(2):104-110. doi: 10.1016/j.ymgme.2017.04.012. Epub 2017 Apr 28.

  PMID: 28465125 DERIVED

Related Links

• BH4 \& PKU Study Opportunity

Biospecimen

Retention: SAMPLES WITH DNA

Blood plasma Blood platelets Whole blood Urine

MeSH Terms

Conditions

Phenylketonurias

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Rani H. Singh
• Organization: Emory University

rsingh@emory.edu

404-448-8519

Study Officials

• Rani H Singh, PhD, RD

  Emory University Department of Human Genetics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 29, 2008
• First Posted: June 3, 2008
• Study Start: October 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: June 8, 2015
• Results First Posted: August 20, 2014

Record last verified: 2015-05

Locations

US (2)