Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy

Conditions
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Hyperphenylalaninemia, Phenylketonuria

Intervention / Treatment
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* Drug: Sapropterin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Non-Kuvan treated<br>Adults with hyperphenylalaninemia who have are not receiving Kuvan therapy. | |
| Experimental: Kuvan treated<br>Adults with hyperphenylalaninemia who are treated with Kuvan (sapropterin). | Drug: Sapropterin<br>* 20 mg/kg, orally, daily, 1 year or patient chooses to discontinue therapy<br>* Other names: Kuvan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density | A DXA scan will be conducted one year after Kuvan therapy is initiated. | 1 year after initiation of Kuvan therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Amino Acid Profile | Evaluation of levels of plasma amino acids. | every three months up to 1 year | 
| Diet Analysis | 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. | every 3 months up to 1 year | 
| Plasma Phenylalanine Levels | Plasma phenylalanine levels will be monitored to determine effectiveness of Kuvan therapy. | weekly for 6 weeks, then at least every three months up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperphenylalaninemia, Phenylketonuria, Adults, Bone Mineral Density