NCT01706965

Kuvan in People With Schizophrenia and Schizoaffective Disorder

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: New York State Psychiatric Institute · Academic / Other
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Not accepted

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)

Conditions

• Schizophrenia
• Schizoaffective Disorder

Interventions

Type	Name	Description
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
DRUG	Multivitamin	Multi-vitamin will be used as an active control in this study. Will be dosed daily

Timeline

• Start date: 2012-10-01
• Primary completion: 2016-06-01
• Completion: 2016-06-01
• First posted: 2012-10-15
• Last updated: 2017-09-13
• Results posted: 2017-09-13

Locations

1 site across 1 country: United States