Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Heather Saavedra, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT01541397
First received: July 11, 2011
Last updated: February 23, 2012
Last verified: February 2012

July 11, 2011
February 23, 2012
June 2011
October 2012   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01541397 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy
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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hyperphenylalaninemia
  • Phenylketonuria
Drug: Sapropterin
20 mg/kg, orally, daily, 1 year or patient chooses to discontinue therapy
Other Name: Kuvan
  • 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.
    Intervention: Drug: Sapropterin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Enrolling by invitation
20
October 2012
October 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01541397
HSC-MS-11-0119
No
Heather Saavedra, The University of Texas Health Science Center, Houston
The University of Texas Health Science Center, Houston
BioMarin Pharmaceutical
Principal Investigator: Heather W Saavedra, MS The University of Texas Health Science Center, Houston
The University of Texas Health Science Center, Houston
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP