Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy

NCT ID: NCT01541397

Last Updated: 2015-07-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2012-08-31

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.

Conditions

Hyperphenylalaninemia; Phenylketonuria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Non-Kuvan treated

Adults with hyperphenylalaninemia who have are not receiving Kuvan therapy.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Kuvan treated

Adults with hyperphenylalaninemia who are treated with Kuvan (sapropterin).

Group Type: EXPERIMENTAL

Sapropterin

Intervention Type: DRUG

20 mg/kg, orally, daily, 1 year or patient chooses to discontinue therapy

Interventions

Sapropterin

20 mg/kg, orally, daily, 1 year or patient chooses to discontinue therapy

Intervention Type: DRUG

Other Intervention Names

Kuvan

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Heather Saavedra

Nutritionist; Department of Pediatrics Division of Genetics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Heather W Saavedra, MS

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Countries

United States

Other Identifiers

HSC-MS-11-0119

Identifier Type: -

Identifier Source: org_study_id