Pimavanserin PET Tracer for Neurodegenerative Disease

Overseen By Levi Pettit, BA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt University Medical Center

Must not be taking: Serotonergics, Antipsychotics, Pimavanserin

Disqualifiers: Stroke, Neurological illness, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new treatment, using a special brain scan, affects individuals with neurodegenerative diseases like Parkinson’s or Huntington’s. Researchers aim to determine if brain activity differs between these patients and healthy individuals. The study employs a PET scan to examine specific brain receptors. One treatment under study is Pimavanserin, used for Parkinson’s with frequent hallucinations or delusions. Individuals with Parkinson’s who experience these symptoms and have not recently used certain medications might be suitable candidates. Participants will need a study partner to assist with study visits. As a Phase 4 trial, this research seeks to understand how an already FDA-approved and effective treatment can benefit more patients.

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.

What is the safety track record for these treatments?

Research shows that Pimavanserin is usually well-tolerated by people with mental health symptoms related to brain diseases. Studies have found that it does not impair thinking, memory, or movement. However, some people have reported side effects such as sleep issues and changes in thinking. Monitoring for these effects is important, but overall, the treatment is considered manageable. Always consult a doctor to understand how it might affect you personally. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for neurodegenerative diseases focus on alleviating symptoms rather than targeting the root cause. But Pimavanserin stands out because it works differently by targeting serotonin 2A receptors, which are believed to play a role in the cognitive and behavioral symptoms of these diseases. Researchers are excited about Pimavanserin because it has the potential to improve not just the symptoms, but also the overall brain function, offering a new hope for better management of neurodegenerative conditions. Additionally, the use of the [18F]MH.MZ PET tracer in this trial could provide deeper insights into how these diseases affect the brain, potentially leading to more precise and effective treatments in the future.

What evidence suggests that this trial's treatments could be effective for neurodegenerative disease?

Research has shown that pimavanserin reduces hallucinations and delusions in people with Parkinson's disease psychosis. Studies found that patients taking pimavanserin had significantly better symptom scores than those on a placebo. In one study, 47% of patients experienced symptom improvement, with some groups seeing even better results. Pimavanserin works by affecting the 5-HT2A receptor in the brain, which is believed to be involved in these symptoms. This treatment is already approved for certain conditions, demonstrating its effectiveness. Participants in this trial will receive pimavanserin to further investigate its effects on neurodegenerative diseases. ^{1 6 7 8 9}

Who Is on the Research Team?

Richard Darby, MD

Principal Investigator

Vanderbilt University Medical Center

Ciaran Considine, PhD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• [18F]MH.MZ
• Pimavanserin

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.

How Is the Trial Designed?

Group I: Pimavanserin Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

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)

Published Research Related to This Trial

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 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]

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]

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]

In a study of 64 patients with suspected neurodegenerative diseases, early-phase PET imaging using both [18F]PI-2620 tau and [18F]flutemetamol amyloid tracers showed high correlations in detecting brain perfusion deficits, particularly in the frontal and parietal lobes.

Both tracers can effectively serve as dual-purpose diagnostic tools, providing insights into amyloid/tau pathology and neuronal activity, which could enhance the assessment of neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of perfusion deficit with early phases of [18F]PI-2620 tau-PET versus [18F]flutemetamol-amyloid-PET recordings. Völter, F., Beyer, L., Eckenweber, F., et al.[2023]

Citations

1.

nuplazidhcp.com

nuplazidhcp.com/efficacy-data

Efficacy Data - NUPLAZID® (pimavanserin)

The mean SAPS-PD baseline score was 15.9 (6.12) for NUPLAZID and 14.7 (5.55) for placebo.1,2 The majority of patients were on PD medications at entry; these ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10977351/

Safety Profile of Pimavanserin Therapy in Elderly Patients ...

This trial evaluated the effects of pimavanserin compared to placebo in frail older adults and elderly patients with neuropsychiatric symptoms related to NDD.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00658567

A Study of Safety and Efficacy of Pimavanserin (ACP-103) ...

Study Overview. This study will evaluate the safety and efficacy of two dose levels of pimavanserin (ACP-103) compared to placebo in patients with Parkinson's ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9036130/

Long-term outcomes with pimavanserin for psychosis in ...

Initial improvement was seen in 47% of the entire group, and 50% of the DLB patients. Additional antipsychotic medication was needed ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S1353802021001450

Efficacy results of pimavanserin from a multi-center, open- ...

Pimavanserin, a selective 5-HT 2A inverse agonist/antagonist, was approved for hallucinations and delusions associated with Parkinson's disease psychosis (PDP).

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38427485/

Safety Profile of Pimavanserin Therapy in Elderly Patients ...

Pimavanserin was well tolerated and not associated with motor or cognitive impairment. Together, these findings highlight the manageable and generally ...

7.

nuplazidhcp.com

nuplazidhcp.com/safety-tolerability-data

Safety and Tolerability Data | NUPLAZID® (pimavanserin)

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. · NUPLAZID is not approved for the treatment ...

8.

alz-journals.onlinelibrary.wiley.com

alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.076487

Safety profile of pimavanserin therapy in elderly patients with ...

Pimavanserin was well tolerated in patients with neuropsychiatric symptoms related to neurodegenerative disease, consistent with the known safety profile of ...

9.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0165032724011613

Comprehensive analysis of adverse events associated with ...

This study reveals potential AEs of pimavanserin, including sleep disorders and cognitive changes, underscoring the importance of careful monitoring and ...