Study of Kuvan Treatment in Adults With GTPCH Deficiency

Phase 1

Completed

Brief Summary: The purpose of this study is to identify the dose of Kuvan needed to normalize the levels of tetrahydrobiopterin (BH4) in patients with a Guanosine Triphosphate Cyclohydrolase (GTPCH) deficiency and to asses the potential impact of oral Kuvan on mood and function in individuals with GTPCH deficiency who may be experiencing symptoms of anxiety, depression, fatigue, trouble concentrating, or memory loss. This will be a phase one study. The investigators will monitor patients over a period of three to six months while on the medication. Medication levels will be monitored by measuring the BH4 levels in cerebral spinal fluid (CSF). Patients will undergo a baseline lumbar puncture and two follow-up lumbar punctures for this purpose. The investigators will also monitor emotional function and motor function.

Recruitment & Eligibility

Inclusion Criteria

established diagnosis of GTPCH deficiency, supported by appropriate family history, CSF neurotransmitter studies, skin fibroblast enzyme assay and/or mutation analysis
minimum age 18 years
identified by self or others to have symptoms of anxiety, depression, fatigue, or other neurocognitive dysfunction (trouble concentrating, memory loss, etc)
willingness to undergo at least 2 CSF evaluations for BH4 and neurotransmitter levels over an 8 to 12 week period

Exclusion Criteria

age < 18 years old
unwillingness to undergo repeated CSF analysis
lack of supporting diagnostic criteria
concomitant medical problems or medications which would increase risk of Kuvan®
concomitant psychiatric state, such as severe depression with suicidal ideation that requires immediate referral and alternative treatment intervention
prior history of back surgery, abnormality or chronic pain that in the opinion of the investigator would increase risks associated with lumbar puncture
significant obesity that might increase difficulty or risk in performing lumbar puncture
if female, unwillingness to use birth control during the period of study drug administration

Arm && Interventions

Group	Intervention	Description
Kuvan Cohort 2	Sapropterin	Participants in cohort 2 will be enrolled after the analysis of cohort 1 data has taken place. Dosing for cohort 2 will be based on results obtained in cohort 1, but will plan on starting at 30 mg/kg/day.
Kuvan Cohort 1	Sapropterin	This cohort will be enrolled first. Analysis will be done to determine the optimum dosing of Kuvan to normalize BH4 levels in the Cerebral Spinal Fluid. This cohort will begin at a dose of 20mg/kg/day.

Primary Outcome Measures

Name	Time	Method
Change in BH4 Levels in Cerebral Spinal Fluid	Baseline, 8 wks, 12 wks	Identify dosing range of oral Kuvan® necessary and sufficient to normalize CSF BH4 levels in adults with GTPCH Deficiency.

Secondary Outcome Measures