Pimavanserin PET Tracer for Neurodegenerative Disease

Recruiting in Palo Alto (17 mi)

Overseen by Daniel Claassen

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Vanderbilt University Medical Center

Must not be taking: Serotonergics, Antipsychotics, Pimavanserin

Disqualifiers: Stroke, Neurological illness, Pregnancy, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests if pimavanserin can help improve psychosis symptoms in Parkinson's Disease patients by affecting specific brain receptors. Pimavanserin is an atypical antipsychotic approved for treating hallucinations and delusions in Parkinson's disease psychosis. The study uses brain scans to measure changes over time.

Will I have to stop taking my current medications?

The trial requires that you stop using serotonergic medications (medications that affect serotonin levels) for at least 6 weeks and antipsychotics for at least 2 weeks before participating.

How does the drug Pimavanserin PET Tracer differ from other treatments for neurodegenerative disease?

Pimavanserin PET Tracer is unique because it is used as a diagnostic tool to visualize and track protein deposits in the brain, which are associated with neurodegenerative diseases. Unlike traditional treatments that aim to alleviate symptoms, this tracer helps in the early detection and monitoring of disease progression by providing detailed brain imaging. ^{1 2 3 4 5}

Research Team

Daniel Claassen

Principal Investigator

Vanderbilt University Medical Center

Ciaran Considine, PhD

Principal Investigator

Vanderbilt University Medical Center

Richard Darby, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for people with neurodegenerative diseases like Parkinson's, Lewy body disease, and others who experience psychosis. Participants need a study partner and must not have had strokes or serious illnesses that could interfere with the study. Pregnant women and those on certain medications recently are excluded.

Inclusion Criteria

I have been diagnosed with a neurodegenerative disease like Parkinson's or Huntington's.

I am the same age and gender as the patient group.

Study partner available for study visits

Exclusion Criteria

Contra-indication or inability to tolerate MRI scan

Pregnant or breastfeeding women

I have Parkinson's and have taken or am taking pimavanserin.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

PET and MRI scans are conducted to measure baseline 5HT2A receptor density and functional connectivity

1 week

1 visit (in-person)

Treatment

Participants receive pimavanserin for 6 weeks, with follow-up PET and MRI scans to assess changes

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in psychosis severity and functional connectivity

4 weeks

Treatment Details

Interventions

• [18F]MH.MZ (Serotonin 2A Receptor PET Tracer)
• Pimavanserin (Antipsychotic)

Trial Overview The trial is testing how a PET tracer called [18F]MH.MZ binds to serotonin receptors in patients compared to healthy controls. It aims to show differences in receptor occupancy between these groups using this imaging technique.

Participant Groups

Group I: Pimavanserin Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Jeffrey R. Balser

Vanderbilt University Medical Center

Chief Executive Officer since 2009

MD and PhD from Vanderbilt University

Rick W. Wright

Vanderbilt University Medical Center

Chief Medical Officer since 2023

MD from University of Missouri-Columbia

ACADIA Pharmaceuticals Inc.

Industry Sponsor

Trials

49

Recruited

11,700+

Founded

1993

Headquarters

San Diego, USA

Known For

Neurological Disorders

Top Products

Nuplazid (pimavanserin), Daybue (trofinetide)

Findings from Research

The tau PET tracer [18F]SNFT-1 shows high selectivity and affinity for tau aggregates in Alzheimer's disease brains, outperforming other tau PET tracers in terms of signal-to-background ratio.

Preclinical studies indicate that [18F]SNFT-1 has favorable pharmacokinetics, with high initial brain uptake and rapid washout, making it a promising candidate for monitoring tau pathology in aging and neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Characterization of the Tau PET Tracer [18F]SNFT-1: Comparison of Tau PET Tracers. Harada, R., Lerdsirisuk, P., Shimizu, Y., et al.[2023]

Several PET tracers are now clinically available for detecting amyloid-beta (Aβ) plaques in the brains of patients being evaluated for Alzheimer's disease, improving diagnostic accuracy for cognitive impairments.

Research is actively progressing on tau and α-synuclein tracers, which could enhance early diagnosis and monitoring of neurodegenerative diseases like Alzheimer's and Parkinson's, although tau tracers are still in clinical development and α-synuclein tracers are in the early research phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New protein deposition tracers in the pipeline. Jovalekic, A., Koglin, N., Mueller, A., et al.[2023]

The novel tau imaging agent [18F]N-methyl lansoprazole ([18F]NML) was successfully synthesized and validated for clinical use, showing good radiochemical purity and safety in a study involving 15 participants, with no adverse effects reported.

Despite its high affinity for tau aggregates in laboratory tests, [18F]NML demonstrated low brain retention and lacked specific imaging signals in patients with mild cognitive impairment and Alzheimer's disease, leading to the conclusion that further development of this agent is not justified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of [18F]-N-Methyl lansoprazole as a Tau PET Imaging Agent in First-in-Human Studies. Kramer, V., Brooks, AF., Haeger, A., et al.[2021]

The radiotracer [18F]AV-1451, used for PET imaging of tau protein aggregates, shows off-target accumulation in areas with low tau levels, likely due to its weak inhibition of monoamine oxidase (MAO) enzymes.

This study confirms that MAO inhibitors can significantly affect the binding of [18F]AV-1451, suggesting that off-target effects should be considered when interpreting PET imaging results in neurodegenerative disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of AV-1451 as a Weak, Nonselective Inhibitor of Monoamine Oxidase. Drake, LR., Pham, JM., Desmond, TJ., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Preclinical Characterization of the Tau PET Tracer [18F]SNFT-1: Comparison of Tau PET Tracers. [2023]

2. England pubmed.ncbi.nlm.nih.gov

New protein deposition tracers in the pipeline. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Evaluation of [18F]-N-Methyl lansoprazole as a Tau PET Imaging Agent in First-in-Human Studies. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Identification of AV-1451 as a Weak, Nonselective Inhibitor of Monoamine Oxidase. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Assessment of perfusion deficit with early phases of [18F]PI-2620 tau-PET versus [18F]flutemetamol-amyloid-PET recordings. [2023]