Study of Kuvan Treatment in Adults With GTPCH Deficiency

NCT01425528 | Completed Phase 1 Results DMC

• 1 other identifier: 48052
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

GTP Cyclohydrolase Deficiency

Outcome Measures

Primary Outcomes (1)

• Change in BH4 Levels in Cerebral Spinal Fluid

  Identify dosing range of oral Kuvan® necessary and sufficient to normalize CSF BH4 levels in adults with GTPCH Deficiency.

  Baseline, 8 wks, 12 wks

Study Arms (2)

Kuvan Cohort 1

EXPERIMENTAL

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.

Drug: Sapropterin

Kuvan Cohort 2

EXPERIMENTAL

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.

Drug: Sapropterin

Interventions

Sapropterin DRUG

Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1.

Also known as: Kuvan

Kuvan Cohort 1; Kuvan Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Utah: lead
• BioMarin Pharmaceutical: collaborator

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Interventions

sapropterin

Results Point of Contact

• Title: Kathryn Swoboda MD
• Organization: University of utah

Swoboda@genetics.utah.edu

801-585-9717

Study Officials

• Kathryn J Swoboda, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2011
• First Posted: August 30, 2011
• Study Start: August 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: April 1, 2025
• Results First Posted: April 8, 2014

Record last verified: 2014-03

Locations

US (1)