Open-label study to evaluate VMAT2 inhibition in psychosis
Research type
Research Study
Full title
An Open-label Positron Emission Tomography Study to Evaluate the Effects of Vesicular Monoamine Transporter 2 Receptor (VMAT2) Blockade on the Dopamine Neurotransmitter System in Subjects with Positive Symptoms and a Diagnosis of Schizophrenia or Schizoaffective Disorder
IRAS ID
300422
Contact name
Oliver D Howes
Contact email
Sponsor organisation
Neurocrine Biosciences Inc.
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Antipsychotic treatment is inadequate for many patients with schizophrenia or schizoaffective disorder. The mechanism underlying persistent symptoms despite antipsychotic treatment is unknown, but several lines of evidence implicate the dopamine system. This study will investigate the role of the dopamine system in treatment-resistant psychosis by measuring dopamine synthesis capacity and levels of vesicular monoamine transporter 2 (VMAT2) in healthy volunteers and in patients with schizophrenia or schizoaffective disorder with ongoing positive symptoms of psychosis. This will help identify new approaches to treat ongoing positive symptoms of psychosis despite antipsychotic treatment for patients with schizophrenia or schizoaffective disorder.
In lay terms, the study addresses the following questions:
1. Does VMAT2 inhibition affect dopamine synthesis capacity in patients with persistent positive symptoms?
2. Do dopamine synthesis capacity and VMAT2 density relate to clinical symptoms in patients with schizophrenia and schizoaffective disorder at baseline and after VMAT2 inhibition?
3. Are VMAT2 levels and dopamine synthesis capacity elevated in patients relative to healthy controls?The third question will be answered by a cross-sectional case-control study. Patient participants and healthy volunteers aged 21-85 will undergo assessments to determine eligibility. There will then be two PET imaging visits using [18F]DOPA and [18F]AV-133 tracers to measure dopamine synthesis capacity and VMAT2 levels. Patient and healthy volunteers' PET imaging measures will then be compared.
The first and second questions will be answered by a nested longitudinal observational study of the effect of VMAT2 inhibition on dopamine synthesis capacity in the patients group. Eligible patient candidates with ongoing positive symptoms will then enter the longitudinal arm and receive a VMAT2 inhibitor (valbenazine) orally for up to 41 days. Following this, initial PET imaging measures will be repeated and valbenazine stopped. Follow-up imaging measures ([18F]DOPA and [18F]AV-133) will then be compared to baseline imaging measures.
Duration:up to 12weeks for healthy volunteers and 16weeks for patient participants.
REC name
East of Scotland Research Ethics Service REC 2
REC reference
22/ES/0003
Date of REC Opinion
23 Feb 2022
REC opinion
Further Information Favourable Opinion