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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by Emory University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
BioMarin Pharmaceutical
Clinical Interaction Network (CIN) of the Atlanta
Atlanta Clinical and Translational Science Institute
Information provided by:
Emory University
ClinicalTrials.gov Identifier:
NCT00688844
First received: May 29, 2008
Last updated: September 24, 2009
Last verified: July 2009
  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
Phenylketonuria

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:
  • Changes in body composition: fat mass, lean mass, bone density, anthropometrics [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Nutritional status: Changes in blood nutrition markers, macronutrient intake and micronutrient intake [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Changes in blood and urine neurotransmitter concentrations (catecholamines and serotonin) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood plasma Blood platelets Whole blood Urine


Enrollment: 62
Study Start Date: October 2008
Estimated Study Completion Date: February 2010
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
PKU subjects starting KuvanTM therapy.

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
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
Clinical Interaction Network (CIN) of the Atlanta
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 H. Singh, PhD, RD, Emory University Department of Human Genetics
ClinicalTrials.gov Identifier: NCT00688844     History of Changes
Other Study ID Numbers: IRB-7828
Study First Received: May 29, 2008
Last Updated: September 24, 2009
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 April 23, 2014