Clinical trial NCT00688844: 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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Phenylketonuria
Keywords: PKU
Phenylketonuria
BH4
Kuvan
Tetrahydrobiopterin
Sapropterin Dihydrochloride
Nutrition
PHE
Phenylalanine
PAH
Phenylalanine hydroxylase
Neurotransmitters
Serotonin
Catecholamines
Diet
Body Fat
Bone Density
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: BioMarin Pharmaceutical
name: Atlanta Clinical and Translational Science Institute
First posted: 2008-06-03
Enrollment: 58
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: Change From Baseline in BMI at 12 Months
timeFrame: Baseline and 12 months
measure: Change From Baseline in Bone Mineral Density (BMD) at 12 Months
timeFrame: Baseline and 12 months
measure: Change From Baseline in Percent (%) Lean Mass at 12 Months
timeFrame: Baseline and 12 months
measure: Change From Baseline in Percent (%) Fat Mass at 12 Months
timeFrame: Baseline and 12 months
measure: Change From Baseline in Plasma Phenylalanine at 12 Months
timeFrame: Baseline and 12 months
measure: Change From Baseline in Total Dietary Protein Intake at 12 Months
timeFrame: Baseline and 12 months
measure: Change From Baseline in Phenylalanine Intake at 12 Months
timeFrame: Baseline and 12 months
Secondary outcomes:
Other outcomes:
measure: Change From Baseline in Serotonin at 12 Months
timeFrame: Baseline and 12 months
Locations:
city: Atlanta
country: United States
facility: Emory Hospital, CIN/ACTSI
state: Georgia
city: Decatur
country: United States
facility: Emory University Genetics Clinic
state: Georgia
Study officials:
affiliation: Emory University Department of Human Genetics
name: Rani H Singh, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.