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

May 13, 2015 updated by: Rani Singh, Emory University

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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: The investigators 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: Investigators 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.

Study Type

Observational

Enrollment (Actual)

58

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory Hospital, CIN/ACTSI
      • Decatur, Georgia, United States, 30033
        • Emory University Genetics Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PKU subjects - baseline
Male and female subjects with PKU at baseline 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:
  • Kuvan
  • BH4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in BMI at 12 Months
Time Frame: Baseline and 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
Time Frame: Baseline and 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
Time Frame: Baseline and 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
Time Frame: Baseline and 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
Time Frame: Baseline and 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
Time Frame: Baseline and 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
Time Frame: Baseline and 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Serotonin at 12 Months
Time Frame: Baseline and 12 months
Objective: 1 year prospective cohort of PKU patients introduced to sapropterin (Kuvan)to evaluate peripheral neurotransmitter changes across time.
Baseline and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

BioMarin Pharmaceutical
Atlanta Clinical and Translational Science Institute

Investigators

  • Principal Investigator: Rani H Singh, PhD, RD, Emory University Department of Human Genetics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (ACTUAL)

October 1, 2010

Study Completion (ACTUAL)

October 1, 2010

Study Registration Dates

First Submitted

May 29, 2008

First Submitted That Met QC Criteria

June 2, 2008

First Posted (ESTIMATE)

June 3, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

June 8, 2015

Last Update Submitted That Met QC Criteria

May 13, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00007828

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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