We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00688844
Recruitment Status : Completed
First Posted : June 3, 2008
Results First Posted : August 20, 2014
Last Update Posted : June 8, 2015
Sponsor:
Collaborators:
BioMarin Pharmaceutical
Atlanta Clinical and Translational Science Institute
Information provided by (Responsible Party):
Rani Singh, Emory University

Tracking Information
First Submitted Date May 29, 2008
First Posted Date June 3, 2008
Results First Submitted Date August 5, 2013
Results First Posted Date August 20, 2014
Last Update Posted Date June 8, 2015
Study Start Date October 2008
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 13, 2015)
  • 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
  • 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
  • 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)
  • 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)
  • 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.
  • 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
  • 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
Original Primary Outcome Measures
 (submitted: June 2, 2008)
  • Changes in body composition: fat mass, lean mass, bone density, anthropometrics [ Time Frame: 12 months ]
  • Nutritional status: Changes in blood nutrition markers, macronutrient intake and micronutrient intake [ Time Frame: 12 months ]
  • Changes in blood and urine neurotransmitter concentrations (catecholamines and serotonin) [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: July 30, 2014)		 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Nutritional and Neurotransmitter Changes in PKU Subjects on BH4
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.
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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood plasma Blood platelets Whole blood Urine
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.
Condition Phenylketonuria
Intervention 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
Study Groups/Cohorts PKU subjects - baseline
Male and female subjects with PKU at baseline starting KuvanTM therapy.
Intervention: Drug: KuvanTM Therapy
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: July 30, 2014)		 58
Original Estimated Enrollment
 (submitted: June 2, 2008)		 105
Actual Study Completion Date October 2010
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages 4 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00688844
Other Study ID Numbers IRB00007828
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Current Responsible Party Rani Singh, Emory University
Original Responsible Party Rani H. Singh, PhD, RD, Emory University Department of Human Genetics
Current Study Sponsor Emory University
Original Study Sponsor Same as current
Collaborators
  • BioMarin Pharmaceutical
  • Atlanta Clinical and Translational Science Institute
Investigators
Principal Investigator: Rani H Singh, PhD, RD Emory University Department of Human Genetics
PRS Account Emory University
Verification Date May 2015