Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy
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 Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy|
- Bone Mineral Density [ Time Frame: 1 year after initiation of Kuvan therapy ] [ Designated as safety issue: No ]A DXA scan will be conducted one year after Kuvan therapy is initiated.
- Plasma Amino Acid Profile [ Time Frame: every three months up to 1 year ] [ Designated as safety issue: No ]Evaluation of levels of plasma amino acids.
- Diet Analysis [ Time Frame: every 3 months up to 1 year ] [ Designated as safety issue: No ]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.
- Plasma Phenylalanine Levels [ Time Frame: weekly for 6 weeks, then at least every three months up to 1 year ] [ Designated as safety issue: No ]Plasma phenylalanine levels will be monitored to determine effectiveness of Kuvan therapy.
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||October 2012|
|Estimated Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
No Intervention: Non-Kuvan treated
Adults with hyperphenylalaninemia who have are not receiving Kuvan therapy.
Experimental: Kuvan treated
Adults with hyperphenylalaninemia who are treated with Kuvan.
20 mg/kg, orally, daily, 1 year or patient chooses to discontinue therapy
Other Name: Kuvan
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.
|United States, Texas|
|The University of Texas Health Science Center at Houston|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Heather W Saavedra, MS||The University of Texas Health Science Center, Houston|