MIMIC 1.0
Research type
Research Study
Full title
Muscarinic Influences on Striatal Dopamine: A Molecular Imaging Study With [11C]-PHNO PET
IRAS ID
354854
Contact name
Oliver Howes
Contact email
Sponsor organisation
Vice President (Research and Innovation) King’s College London
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Psychotic disorders such as schizophrenia are a cause of major disability. The symptoms of schizophrenia are grouped into positive (e.g. delusions and hallucinations), negative (e.g. social withdrawal, lack of motivation) and cognitive symptoms (e.g. difficulty with concentration and memory or problem-solving). Current medication for psychosis is often effective at addressing positive symptoms, but not negative and cognitive symptoms.
Current antipsychotic treatment work on receptors in the brain called dopamine D2 receptors to reduce a chemical called dopamine. Recently, several medications with novel mechanisms of action have been investigated for the treatment of schizophrenia. This includes a medication called xanomeline-trospium, which has been shown to have good results in clinical trials for people experiencing acute psychosis. It is currently unclear, however, to what extent xanomeline-trospium works by reducing dopamine activity in the brain, like current antipsychotic treatments, or whether its effects come from a different mechanism (e.g. via another system called the muscarinic system). Understanding how xanomeline-trospium works will help to optimise their use in clinical practice and inform drug development.
To investigate this, the study will use a ‘radiotracer’ called 11-C-PHNO. This binds to dopamine D2 receptors to show how much dopamine is active in an area of the brain called the striatum. We can use this to show the influence of medications on striatal dopamine signalling. If a drug blocks these receptors directly, it will reduce tracer binding.
The current study will compare PET and MRI brain scans of people with psychotic disorders taking traditional D2 receptor blocking medication to scans after they have changed medications to xanomeline-trospium, to understand how xanomeline-trospium affects dopamine signalling in the brain. We will also compare these brain scans to those who do not have psychosis and are not taking any medication.
Participants with psychosis will undergo three study visits and four brain scans in total; 1 MRI and 1 PET whilst taking their regular medication, and 1 MRI and 1 PET whilst on xanomeline-trospium. After the first set of scans their medication will be gradually switched to xanomeline-trospium for a treatment length of 6 weeks. They will then gradually switch back to their regular medication. Participants without psychosis will undergo 1 MRI and 1 PET only. Study activities will also involve questionnaires about past medical and psychiatric history, questionnaires about symptoms and side effects, and tests of learning and memory on the iPad.
The study will take place at the Institute of Psychiatry, Psychology and Neuroscience (King’s College London) for screening assessments. MRI scans will take place at LMS Steiner Facility, Hammersmith Hospital Campus. PET scans will take place at Perceptive, Burlington Danes Building, Hammersmith Hospital Campus.
A grant from Bristol Myers Squibb (the company that produces xanomeline-trospium) is supporting this study.
REC name
North of Scotland Research Ethics Committee 2
REC reference
26/NS/0008
Date of REC Opinion
15 Feb 2026
REC opinion
Unfavourable Opinion