Clinical trial NCT01541397: Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy
Official title: Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hyperphenylalaninemia
Phenylketonuria
Keywords: Hyperphenylalaninemia
Phenylketonuria
Adults
Bone Mineral Density
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: BioMarin Pharmaceutical
First posted: 2012-03-01
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Bone Mineral Density
timeFrame: 1 year after initiation of Kuvan therapy
Secondary outcomes:
measure: Plasma Amino Acid Profile
timeFrame: every three months up to 1 year
measure: Diet Analysis
timeFrame: every 3 months up to 1 year
measure: Plasma Phenylalanine Levels
timeFrame: weekly for 6 weeks, then at least every three months up to 1 year
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Heather W Saavedra, MS
role: PRINCIPAL_INVESTIGATOR
References: