Kuvan in People With Schizophrenia and Schizoaffective Disorder

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by New York State Psychiatric Institute
Sponsor:
Collaborator:
Stanley Medical Research Institute
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT01706965
First received: October 10, 2012
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

Rater blinded trial of six weeks of Kuvan vs. multivitamin in 60 outpatients with schizophrenia or schizoaffective disorder. The aims are to evaluate an anticipated clinical response to Kuvan treatment including negative symptom and cognitive deficits, evaluate safety of Kuvan treatment for schizophrenic patients and evaluate the relationship of changes in plasma Kuvan levels and efficacy outcomes.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: Kuvan
Drug: Multivitamin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 6R-BH 4 in People With Schizophrenia and Schizoaffective Disorder

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Clinical response to Kuvan [ Time Frame: Baseline (start of Kuvan) through six weeks of treatment and two weeks post-treatment follow up ] [ Designated as safety issue: No ]
    To evaluate an anticipated clinical response to Kuvan treatment including negative symptoms and cognitive deficits by the change in the Positive and Negative Symptom Scale (PANSS) total score and the MATRICS consensus cognitive scale


Secondary Outcome Measures:
  • Safety [ Time Frame: Throughout 6 week treatment study period ] [ Designated as safety issue: Yes ]
    To evaluate the safety of Kuvan treatment for schizophrenic patients by collecting data on all adverse events


Other Outcome Measures:
  • Relationship in changes in plasma Kuvan levels and efficacy outcomes [ Time Frame: Lead-in phase visit, baseline visit and at week 2, 4, and 6 visits ] [ Designated as safety issue: No ]
    Measure plasma BH4 levels and examine the relationship with clinical symptoms and cognitive deficits


Estimated Enrollment: 60
Study Start Date: October 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Kuvan
Kuvan once-daily dosing initiated with 10mg/kg for the first week followed by 20mg/kg for the remaining weeks of the study
Drug: Kuvan
20mg/kg using a daily dosing schedule. To increase tolerability, treatment will be initiated at 10mg/kg for the first week of the study. Given the short length of the trial, no dose adjustments will be made for changes in weight
Other Name: Sapropterin dihydrochloride
Active Comparator: Multivitamin
Daily multivitamin tablet
Drug: Multivitamin
Multi-vitamin will be used as an active control in this study. Will be dosed daily

Detailed Description:

Tetrahydrobiopterin (BH4) is a vital central nervous system (CNS) cofactor that maintains availability of amine neurotransmitters such as dopamine (DA) and serotonin (5HT), and stimulates and modulates the glutamatergic system. Dysregulation of these neurotransmitter systems has been implicated in the pathogenesis of schizophrenia (SZ). A central role of BH4 in schizophrenia is further supported by a study finding a relative deficit of 32% for SZ patients as compared to controls. The observed BH4 deficit is comparable to that reported for genetic BH4 deficiency disorders, supporting its characterization as having physiological significance. This highly significant finding, along with: a) the known roles of BH4 in neurotransmitter maintenance, b) dysregulation of CNS neurotransmitter synthesis observed in human BH4 deficiencies, c) evidence that plasma biopterin levels are correlated with CNS biopterin levels, and d) evidence that urinary biopterin excretion is not increased in SZ, all support our hypothesis that dysregulation of BH4 biosynthesis is involved in the pathophysiology of SZ. Moreover, additional data suggesting that mood stabilizer drugs can moderately increase levels of biopterin in patients with psychiatric disorders, and the reported efficacy of BH4 in pilot studies of neuropsychiatric disorders, suggest that alleviation of the schizophrenia BH4 deficit via treatment with synthetic BH4 supplement (Sapropterin dihydrochloride or Kuvan), may give rise to an improvement of the symptoms of schizophrenia, including positive and negative symptoms as well as neurocognitive deficits. Sapropterin dihydrochlorides, teh active pharmaceutical ingredient in Kuvan Tablets,is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4)

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female outpatients with schizophrenia or schizoaffective disorder
  • Ages 18-64
  • A score of 45 or greater on PANSS
  • All oral and depot antipsychotics (with the exception of clozapine) are allowable. Patients must be on their antipsychotic medication for 3 months and stable on dose of antipsychotic and adjunctive medications for 2 weeks prior to study entry. If a patient is on depot medication, they must be stable in dose for 2 months

Exclusion Criteria:

  • Organic brain disorder, including epilepsy; mental retardation; or a medical condition whose pathology or treatment would likely alter the presentation or treatment of schizophrenia
  • Participated in any investigational study or taken an investigational drug within 30 days
  • Current Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of drug/alcohol abuse in last month and current DSM-IV diagnosis drug/alcohol dependence in last 6 months. Subjects must have a negative drug screen at baseline (with one retest allowed for suspected false positive based on clinical judgement of the investigator)
  • Diagnosis of any known BH4 deficiency disorder (other than schizophrenia or schizoaffective disorder), including dopa-responsive dystonia,phenylketonuria (PKU), and autism
  • Current treatment with clozapine
  • In the investigator's judgment, a significant risk of suicide or violent behavior
  • Current use of levodopa and nitric oxide-mediated vasorelaxation or oral minoxidil
  • Women will be excluded if they are pregnant, lactating, or not either surgically-sterile or using appropriate methods of birth control. Women must agree to continue using applicable birth control throughout the trial. All women of child-bearing potential must have a negative urine pregnancy test at the screening visit and visit 2 (1 week before beginning study medication)
  • Absolute neutrophil count below 2.0 on screening
  • Any contraindication or allergic reaction to previous multi-vitamin or unwillingness to stop use of current multi-vitamin during study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01706965

Contacts
Contact: Joshua T Kantrowitz, MD 646-774-6738 kantrow@nyspi.columbia.edu

Locations
United States, New York
New York State Psychiatric Institute Recruiting
New York, New York, United States, 10032
Principal Investigator: Jeffrey A. Lieberman, MD         
Sponsors and Collaborators
New York State Psychiatric Institute
Stanley Medical Research Institute
Investigators
Principal Investigator: Jeffrey A Lieberman, M.D. New York State Psychiatric
  More Information

No publications provided

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01706965     History of Changes
Other Study ID Numbers: 6320
Study First Received: October 10, 2012
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on July 24, 2014