Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy

Not Applicable

Terminated

• Conditions: Hyperphenylalaninemia; Phenylketonuria
• Interventions: Drug: Sapropterin

• Registration Number: NCT01541397
• Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary

Prospective study to compare the bone mineral density in adults with HPA on KUVAN™ therapy to those not on therapy. The investigators hypothesize that after one year of KUVAN™ therapy, there will be an improvement in their bone mineral density.

Detailed Description

Hyperphenylalaninemia (HPA) is a rare metabolic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH) (NIH, October 16-18, 2000). Elevated plasma levels of phenylalanine (phe) cause mental retardation, microcephaly, delayed speech, seizures, eczema, and behavior abnormalities. Adequate control of the plasma levels of phe by a phe-restricted diet can prevent the developmental and behavioral problems.

The foundation of this diet is a phe-free metabolic medical product/formula made from free amino acids. Based on longitudinal studies, it has been reported that the most benefit is attained by individuals who maintain a phe-restricted diet throughout life. On December 13, 2007, KUVAN™ (sapropterin dihydrochloride) was approved by the FDA for the indication of reducing blood phe levels in patients with HPA due to BH4 responsive PKU, in conjunction with a phe restricted diet (BioMarin Pharmaceutical Inc., Investigator's Brochure March 25, 2008). Studies were performed to determine a definition of response to KUVAN™. In a phase 2 clinical trial in 2007, Burton, et. al. defined a Kuvan™ responder as having a 30% or greater improvement in blood phenylalanine levels compared to baseline after 8 days of drug therapy.

Kuvan™ has been shown to improve phenylalanine tolerance in some individuals with HPA. This drug enables these individuals to consume more protein from natural sources. However, there have been no research studies assessing the effects of KUVAN™ along with liberalization of the diet on bone mineral density.

The investigators propose a prospective study to compare the bone mineral density in adults with HPA on KUVAN™ therapy to those not on therapy. The investigators hypothesize that after one year of KUVAN™ therapy, there will be an improvement in their bone mineral density.

Study Timeline

• Study Start: 2011-06
• Study First Submitted: 2011-07-11
• Study First Submitted QC: 2012-02-23
• Study First Posted: 2012-03-01
• Primary Completion: 2012-08
• Study Completion: 2012-08
• Status Verified: 2015-06
• Results First Submitted: 2015-06-11
• Results First Submitted QC: 2015-06-11
• Last Update Submitted: 2015-06-11
• Results First Posted: 2015-07-07
• Last Update Posted: 2015-07-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• Diagnosis of hyperphenylalaninemia at birth
• Age between 18 and 50 years
• Participated in study HSC-MS-110-0262

Exclusion Criteria

• Peri-menopausal and menopausal women will be excluded because this is a time of increased bone loss related to hormonal mediated factors.
• Patients taking bisphosphonates because it alters bone density. Therefore, bone mineral density would reflect the biphosphonate intervention rather than their true status.
• Pregnant women due to the hazard of radiation exposure during a DXA scan. In addition women who have been pregnant or who have breastfed within one year of study enrollment will be excluded because these are periods of rapid bone loss which would not reflect the entity under study but would serve to confound the data.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Kuvan treated	Sapropterin	Adults with hyperphenylalaninemia who are treated with Kuvan (sapropterin).

Primary Outcome Measures

Name	Time	Method
Bone Mineral Density	1 year after initiation of Kuvan therapy	A DXA scan will be conducted one year after Kuvan therapy is initiated.

Secondary Outcome Measures

Name	Time	Method
Plasma Phenylalanine Levels	weekly for 6 weeks, then at least every three months up to 1 year	Plasma phenylalanine levels will be monitored to determine effectiveness of Kuvan therapy.
Plasma Amino Acid Profile	every three months up to 1 year	Evaluation of levels of plasma amino acids.
Diet Analysis	every 3 months up to 1 year	Subjects will provide a 3 day diet record for every plasma amino acid evaluation. Diets will be analyzed to determine phenylalanine, protein, calories, fat, vitamins and minerals.

Trial Locations

Locations (1)

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States