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Kuvan in People With Schizophrenia and Schizoaffective Disorder

Primary Purpose

Schizophrenia, Schizoaffective Disorder

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Kuvan

Multivitamin

About this trial

This is an interventional treatment trial for Schizophrenia

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

New York State Psychiatric Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Kuvan

Multivitamin

Arm Description

Kuvan once-daily dosing initiated with 10mg/kg for the first week followed by 20mg/kg for the remaining weeks of the study

Daily multivitamin tablet

Outcomes

Primary Outcome Measures

Final Positive and Negative Symptom Scale (PANSS)

This is a is a 30 item rating scale widely used in the assessment of schizophrenia ranging from 30-210. Higher scores are worse

Final MATRICS Cognitive Battery

MATRICS assessing 7 domains (Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning, Visual Learning, Reasoning and Problem Solving, and Social Cognition. Raw scores are converted into a composite T-score (normative mean = 50; standard deviation = 10), where higher values indicated less impairment.

Secondary Outcome Measures

Full Information

NCT ID

NCT01706965

First Posted

October 10, 2012

Last Updated

August 14, 2017

Sponsor

New York State Psychiatric Institute

Collaborators

Stanley Medical Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT01706965

Brief Title

Kuvan in People With Schizophrenia and Schizoaffective Disorder

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Completed

Study Start Date

October 2012 (undefined)

Primary Completion Date

June 2016 (Actual)

Study Completion Date

June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

New York State Psychiatric Institute

Collaborators

Stanley Medical Research Institute

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia, Schizoaffective Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Kuvan

Arm Type

Experimental

Arm Description

Kuvan once-daily dosing initiated with 10mg/kg for the first week followed by 20mg/kg for the remaining weeks of the study

Arm Title

Multivitamin

Arm Type

Active Comparator

Arm Description

Daily multivitamin tablet

Intervention Type

Drug

Intervention Name(s)

Kuvan

Other Intervention Name(s)

Sapropterin dihydrochloride

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Multivitamin

Intervention Description

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

Primary Outcome Measure Information:

Title

Final Positive and Negative Symptom Scale (PANSS)

Description

This is a is a 30 item rating scale widely used in the assessment of schizophrenia ranging from 30-210. Higher scores are worse

Time Frame

Baseline (start of Kuvan) and at six weeks of treatment

Title

Final MATRICS Cognitive Battery

Description

Time Frame

Baseline to week 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey A Lieberman, M.D.

Organizational Affiliation

New York State Psychiatric

Official's Role

Principal Investigator

Facility Information:

Facility Name

New York State Psychiatric Institute

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

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Kuvan in People With Schizophrenia and Schizoaffective Disorder

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