Kuvan in People With Schizophrenia and Schizoaffective Disorder

Schizophrenia Clinical Trial

Official title:

6R-BH 4 in People With Schizophrenia and Schizoaffective Disorder

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT01706965
• Other study ID #: 6320
• Status: Suspended
• Phase: Phase 1/Phase 2
• First received: October 10, 2012
• Last updated: March 17, 2016
• Start date: October 2012
• Est. completion date: June 2016

Study information

• Verified date: March 2016
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 60
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

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
• Multivitamin
Multi-vitamin will be used as an active control in this study. Will be dosed daily

Locations

Country	Name	City	State
United States	New York State Psychiatric Institute	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	Stanley Medical Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Relationship in changes in plasma Kuvan levels and efficacy outcomes	Measure plasma BH4 levels and examine the relationship with clinical symptoms and cognitive deficits	Lead-in phase visit, baseline visit and at week 2, 4, and 6 visits	No
Primary	Clinical response to Kuvan	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	Baseline (start of Kuvan) through six weeks of treatment and two weeks post-treatment follow up	No
Secondary	Safety	To evaluate the safety of Kuvan treatment for schizophrenic patients by collecting data on all adverse events	Throughout 6 week treatment study period	Yes