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 Overview

• Status: Terminated
• Conditions: Phenylketonuria; Hyperphenylalaninemia
• Intervention / Treatment: Drug: Sapropterin

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 (sapropterin).	Drug: Sapropterin; 20 mg/kg, orally, daily, 1 year or patient chooses to discontinue therapy; Other Names: Kuvan

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: BioMarin Pharmaceutical
• Investigators: Principal Investigator: Heather W Saavedra, MS, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: July 11, 2011
• First Submitted That Met QC Criteria: February 23, 2012
• First Posted (ESTIMATE): March 1, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): July 7, 2015
• Last Update Submitted That Met QC Criteria: June 11, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Adults; Phenylketonuria; Bone Mineral Density; Hyperphenylalaninemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: HSC-MS-11-0119