Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy

The University of Texas System (UT)

Status

Terminated

Conditions

Hyperphenylalaninemia

Phenylketonuria

Treatments

Drug: Sapropterin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01541397

HSC-MS-11-0119

Details and patient eligibility

About

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.

Full 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.

Enrollment

6 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

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.