Clinical trial NCT05357612: Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases
Official title: Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Neurodegenerative Diseases
Parkinson Disease
Parkinson Disease Psychosis
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: ACADIA Pharmaceuticals Inc.
First posted: 2022-05-03
Enrollment: 75
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: It is hypothesize that patients with clinically diagnosed neurodegenerative diseases will have significantly different receptor occupancy of 5HT2A receptors compared to a healthy age/sex-matched control group. This will be tested by measuring 5HT2A receptor density using the PET radioligand (R)-\[18F\]MH.MZ in both populations.

Detailed description: It is hypothesized that improvement in psychosis symptoms in patients taking pimavanserin will be associated with increased baseline receptor density (Hypothesis 1A), and increased receptor occupancy of 5HT2A receptors following pimavanserin administration (Hypothesis 1B). This will be done by measuring 5HT2A receptor density using the PET radioligand (R)-\[18F\]MH.MZ within predefined symptom networks for hallucinations, delusions, and sleep. A PET scan will be obtained in PD patients with psychosis at enrollment to measure baseline 5HT2A receptor density and then again after 6 weeks of pimavanserin. The change in binding between baseline and post-drug treatment window will be used to measure 5HT2A receptor occupancy.

It is hypothesize that improvement in psychosis symptoms in patients taking pimavanserin will be associated with increased functional connectivity and cerebral blood flow within predefined symptom networks for hallucinations, delusions, and sleep. This will be tested by obtaining MRI scans assessing resting state functional connectivity and arterial spin labeling in PD patients with psychosis at enrollment (baseline) and then again after 6 weeks of pimavanserin.

It is hypothesized that functional neuroimaging changes in response to pimavanserin will be associated with baseline 5HT2A receptor density and 5HT2A receptor occupancy after pimavanserin administration. To test this hypothesis, the differences in functional neuroimaging measures and PET 5HT2A receptor will be measured in PD psychosis patients off (at baseline) and on Pimavanserin (post-treatment window).

Eligibility criteria: Inclusion Criteria:

* Patient arm - clinical diagnosis of Parkinson disease, diffuse Lewy body disease, multiple systems atrophy, Huntington's Disease, Frontotemporal Dementia, and other variants
* Healthy arm - age and gender matched to patient arm
* Psychosis (presence of hallucinations or delusions) starting after the diagnosis of Parkinson's disease, occurring at least weekly for 4 weeks, severe enough to warrant treatment.
* Study partner available for study visits

Exclusion Criteria:

* Prior stroke or other uncontrolled serious neurological or medical illness
* Contra-indication or inability to tolerate MRI scan
* Use of serotonergic medications in the last 6 weeks
* Incapable of providing independent consent.
* Pregnant or breastfeeding women
* psychosis due to a metabolic, toxic, or primary psychiatric disease
* Deemed unable to complete neurocognitive testing
* For PD Participants: current or prior use of pimavanserin
* Use of antipsychotics in the last 2 weeks

Primary outcomes:
measure: Change in 5HT2A receptor density measured using the PET radioligand MH.MZ
timeFrame: Baseline and 6 weeks after intervention of Pimavanserin
measure: Change in 5HT2A receptor binding occupancy measured using the PET radioligand MH.MZ
timeFrame: Baseline and 6 weeks after intervention of Pimavanserin
Secondary outcomes:
measure: Change in psychosis severity
timeFrame: Baseline and 6 weeks after intervention of Pimavanserin
measure: Change in psychosis severity
timeFrame: Baseline and 6 weeks after intervention of Pimavanserin
measure: Changes to functional connectivity and ASL bloodflow
timeFrame: Baseline and 6 weeks after intervention of Pimavanserin
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Daniel Claassen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Ciaran Considine, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Richard Darby, MD
role: PRINCIPAL_INVESTIGATOR
References: