Hyperphenylalaninemia, Phenylketonuria
Conditions
Keywords
Hyperphenylalaninemia, Phenylketonuria, Adults, Bone Mineral Density
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.
Interventions
DRUGSapropterin
20 mg/kg, orally, daily, 1 year or patient chooses to discontinue therapy
Sponsors
BioMarin Pharmaceutical
The University of Texas Health Science Center, Houston
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density | 1 year after initiation of Kuvan therapy | A DXA scan will be conducted one year after Kuvan therapy is initiated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Amino Acid Profile | every three months up to 1 year | Evaluation of levels of plasma amino acids. |
| Diet Analysis | every 3 months up to 1 year | 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 | weekly for 6 weeks, then at least every three months up to 1 year | Plasma phenylalanine levels will be monitored to determine effectiveness of Kuvan therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Non-Kuvan Treated Adults with hyperphenylalaninemia who have are not receiving Kuvan therapy. | 4 |
| Kuvan Treated Adults with hyperphenylalaninemia who are treated with Kuvan (sapropterin).
Sapropterin: 20 mg/kg, orally, daily, 1 year or patient chooses to discontinue therapy | 2 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study ended prior to data collection | 4 | 2 |
Baseline characteristics
| Characteristic | Non-Kuvan Treated | Kuvan Treated | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Bone Mineral Density
A DXA scan will be conducted one year after Kuvan therapy is initiated.
Time frame: 1 year after initiation of Kuvan therapy
Population: Zero participants were analyzed because the study was ended early (due to an insufficient number of enrolled participants).
Secondary
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.
Time frame: every 3 months up to 1 year
Population: Zero participants were analyzed because the study was ended early (due to an insufficient number of enrolled participants).
Secondary
Plasma Amino Acid Profile
Evaluation of levels of plasma amino acids.
Time frame: every three months up to 1 year
Population: Zero participants were analyzed because the study was ended early (due to an insufficient number of enrolled participants).
Secondary
Plasma Phenylalanine Levels
Plasma phenylalanine levels will be monitored to determine effectiveness of Kuvan therapy.
Time frame: weekly for 6 weeks, then at least every three months up to 1 year
Population: Zero participants were analyzed because the study was ended early (due to an insufficient number of enrolled participants).