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Study of Kuvan Treatment in Adults With GTPCH Deficiency

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ClinicalTrials.gov Identifier: NCT01425528
Recruitment Status : Completed
First Posted : August 30, 2011
Results First Posted : April 8, 2014
Last Update Posted : April 8, 2014
Sponsor:
Collaborator:
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Kathryn Swoboda, University of Utah

Study Description
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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.

Condition or disease Intervention/treatment Phase
GTP Cyclohydrolase Deficiency Drug: Sapropterin Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study to Assess Impact of Kuvan® Supplementation as an Adjunct Treatment in Subjects With Dominantly-inherited GTPCH Deficiency on Mood, Behavioral and Motor Phenotypes
Study Start Date : August 2011
Actual Primary Completion Date : August 2013
Actual Study Completion Date : August 2013

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Kuvan Cohort 1
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
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.
Other Name: Kuvan
Experimental: Kuvan Cohort 2
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
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.
Other Name: Kuvan


Outcome Measures
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Primary Outcome Measures :
  1. Change in BH4 Levels in Cerebral Spinal Fluid [ Time Frame: Baseline, 8 wks, 12 wks ]
    Identify dosing range of oral Kuvan® necessary and sufficient to normalize CSF BH4 levels in adults with GTPCH Deficiency.

  2. Change in Neurotransmitter Metabolite Levels in Cerebral Spinal Fluid [ Time Frame: Baseline, 8 wks, 12 wks ]

Secondary Outcome Measures :
  1. Hamilton Anxiety Rating Scale [ Time Frame: Baseline, 8 wks, 12 wks, 24 wks (optional) ]
  2. Hamilton Depression Rating Scale [ Time Frame: Baseline, 8 wks, 12 wks, 24 wks (optional) ]
  3. Behavior Rating Inventory of Executive Function (BRIEF) Adult Version [ Time Frame: Baseline, 8 wks, 12 wks, 24 wks (optional) ]
  4. Beck Depression Inventory [ Time Frame: Baseline, 8 wks, 12 wks, 24 wks (optional) ]
  5. Brief Symptom Inventory [ Time Frame: Baseline, 8 wks, 12 wks, 24 wks (optional) ]
  6. Pittsburgh Sleep Quality Index [ Time Frame: Baseline, 8 wks, 12 wks, 24 wks (optional) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01425528


Locations
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United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Utah
BioMarin Pharmaceutical
Investigators
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Principal Investigator: Kathryn J Swoboda, MD University of Utah
More Information
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Responsible Party: Kathryn Swoboda, Associate Professor, Neurology and Pediatrics Director, Pediatric Motor Disorders Research Program, University of Utah
ClinicalTrials.gov Identifier: NCT01425528    
Other Study ID Numbers: 48052
First Posted: August 30, 2011    Key Record Dates
Results First Posted: April 8, 2014
Last Update Posted: April 8, 2014
Last Verified: March 2014