Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Neurodegenerative Diseases; Parkinson Disease Psychosis
• Intervention / Treatment: Drug: Pimavanserin

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).

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jason Elenberger, MS; Phone Number: 6158751257; Email: jason.elenberger@vumc.org
• Study Contact Backup: Name: Katie Hay, MS; Email: kaitlyn.r.hay@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Jason Elenberger, MS; Phone Number: 615-875-1257; Email: jason.elenberger@vumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pimavanserin	Drug: Pimavanserin; PD related Psychosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 5HT2A receptor density measured using the PET radioligand MH.MZ	Receptor density (Bmax) of 5HT2A receptors measured using the PET radioligand MH.MZ uptake in regions of interest.	Baseline and 6 weeks after intervention of Pimavanserin
Change in 5HT2A receptor binding occupancy measured using the PET radioligand MH.MZ	Receptor binding occupancy (RO) of 5HT2A receptors measured using the PET radioligand MH.MZ uptake in regions of interest.	Baseline and 6 weeks after intervention of Pimavanserin

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in psychosis severity	Change in psychosis severity 6 weeks after starting pimavanserin, as measured by Clinician-Rated Dimensions of Psychosis Symptom Severity (CRD-PSS)18; Domain I (Delusions). Low scores indicate better outcome.	Baseline and 6 weeks after intervention of Pimavanserin
Change in psychosis severity	Change in psychosis severity 6 weeks after starting pimavanserin, as measured by Clinician-Rated Dimensions of Psychosis Symptom Severity (CRD-PSS)18; Domain II (Hallucinations). Low scores indicate better outcome.	Baseline and 6 weeks after intervention of Pimavanserin
Changes to functional connectivity and ASL bloodflow	Changes to functional connectivity and ASL bloodflow (mL/g/min) within pre-defined networks for delusions, hallucinations, and sleep after 6 weeks of Pimavanserin.	Baseline and 6 weeks after intervention of Pimavanserin

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: ACADIA Pharmaceuticals Inc.
• Investigators: Principal Investigator: Daniel Claassen, MD, Vanderbilt University Medical Center; Principal Investigator: Ciaran Considine, PhD, Vanderbilt University Medical Center; Principal Investigator: Richard Darby, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: April 20, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): May 3, 2022

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Parkinson Disease; Neurodegenerative Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Antiparkinson Agents; Anti-Dyskinesia Agents; Pimavanserin
• Other Study ID Numbers: 212028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No