Nutritional and Neurotransmitter Changes in PKU Subjects on BH4 (BH4&PKU)

This study has been completed.
Sponsor:
Collaborators:
BioMarin Pharmaceutical
Atlanta Clinical and Translational Science Institute
Information provided by (Responsible Party):
Rani Singh, Emory University
ClinicalTrials.gov Identifier:
NCT00688844
First received: May 29, 2008
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

HYPOTHESIS: We hypothesize that KuvanTM therapy could influence nutritional and body composition parameters and neurotransmitter concentrations in pediatric and adult PKU subjects.

SUMMARY: Though we know that KuvanTM lowers blood Phe levels and improves tolerance for natural protein in at least half of the PKU (Phenylketonuria) patient population, we 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, we 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, our 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.


Condition Intervention
Phenylketonuria
Drug: KuvanTM Therapy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Baseline Evaluation and Long-term Follow-up of Nutritional Status and Neurotransmitter Concentrations in Phenylketonuria Patients Initiating Treatment With Sapropterin Dihydrochloride (KuvanTM), a Tetrahydrobiopterin Analog.

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Change From Baseline in BMI at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Body mass index (BMI)

  • Change From Baseline in Bone Mineral Density (BMD) at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Bone mineral density (BMD)

  • Change From Baseline in Percent (%) Lean Mass at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    % lean mass was measured via dual energy x-ray absorptiometry (DXA)

  • Change From Baseline in Percent (%) Fat Mass at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Percent fat mass measured via dual energy x-ray absorptiometry (DXA)

  • Change From Baseline in Plasma Phenylalanine at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Full amino acid panel, including phenylalanine, analyzed in fasting plasma samples.

  • Change From Baseline in Total Dietary Protein Intake at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Total dietary protein intake assessed through 3-day food records - calculated as average protein intake (grams/day) in the 3 days recorded

  • Change From Baseline in Phenylalanine Intake at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Total dietary phenylalanine assessed through 3-day food records - calculated as average phenylalanine intake (grams/day) in the 3 days recorded


Other Outcome Measures:
  • Change From Baseline in Serotonin at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Objective: 1 year prospective cohort of PKU patients introduced to sapropterin (Kuvan)to evaluate peripheral neurotransmitter changes across time.


Biospecimen Retention:   Samples With DNA

Blood plasma Blood platelets Whole blood Urine


Enrollment: 58
Study Start Date: October 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
PKU subjects starting KuvanTM therapy.
Drug: KuvanTM Therapy
BH4 treatment was prescribed by each participant's medical provider, not an intervention that was assigned as part of the current study.
Other Names:
  • BH4
  • Kuvan

Detailed Description:

BACKGROUND : Tetrahydrobiopterin (BH4) is a treatment option newly available to phenylketonuria (PKU) patients within the United States as the pharmaceutical KuvanTM. This small molecule functions as a cofactor in multiple enzyme systems, including the metabolism of phenylalanine into tyrosine by the enzyme phenylalanine hydroxylase (PAH).

HYPOTHESIS: We hypothesize that KuvanTM therapy could influence nutritional and body composition parameters and neurotransmitter concentrations in pediatric and adult PKU subjects.

OBJECTIVES:

  1. To record nutritional biomarkers, body composition, bone density, and measures of nutrient intake in a phenylketonuria subject group at baseline and for one year after start of KuvanTM therapy.
  2. To investigate changes in monoamine neurotransmitter synthesis in a phenylketonuria subject group at baseline and for one year after start of KuvanTM therapy.
  3. Evaluate changes in quality of life (QOL) for PKU subjects beginning KuvanTM therapy

METHODOLOGY: We intend to enroll 60 PKU patients, ages 4 to adulthood, who are planning to begin BH4 treatment as prescribed by their medical provider. Patients will be given 4 weeks to demonstrate a response to KuvanTM as determined by a drop in plasma PHE by ≥15%. All patients, regardless of response to KuvanTM, will be allowed to continue in the study. All subjects will be followed for a full 12 months while monitoring nutrient intake, nutritional biomarkers, serotonin and catecholamine levels, and QOL. Two-tailed statistical analysis with α=0.05 will be used to compare results between responders and nonresponders, as well as compare follow-up values with baseline measures.

  Eligibility

Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Pregnant
  • unable to provide informed consent
  • less than 4 years of age
  • currently taking BH4
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00688844

Locations
United States, Georgia
Emory Hospital, CIN/ACTSI
Atlanta, Georgia, United States, 30322
Emory University Genetics Clinic
Decatur, Georgia, United States, 30033
Sponsors and Collaborators
Emory University
BioMarin Pharmaceutical
Atlanta Clinical and Translational Science Institute
Investigators
Principal Investigator: Rani H Singh, PhD, RD Emory University Department of Human Genetics
  More Information

Additional Information:
No publications provided

Responsible Party: Rani Singh, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT00688844     History of Changes
Other Study ID Numbers: IRB00007828
Study First Received: May 29, 2008
Results First Received: August 5, 2013
Last Updated: July 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
PKU
Phenylketonuria
BH4
Kuvan
Tetrahydrobiopterin
Sapropterin Dihydrochloride
Nutrition
PHE
Phenylalanine
PAH
Phenylalanine hydroxylase
Neurotransmitters
Serotonin
Catecholamines
Diet
Body Fat
Bone Density

Additional relevant MeSH terms:
Phenylketonurias
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
Metabolic Diseases
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014