Kuvan in People With Schizophrenia and Schizoaffective Disorder
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 1/Phase 2

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)
    

Intervention name(s): Kuvan; Multivitamin
Intervention type(s): Drug; Drug
Intervention description(s): 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; Multi-vitamin will be used as an active control in this study. Will be dosed daily
Other intervention name(s): Sapropterin dihydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment