Antipsychotics for Lewy Body Disease

(CAMELOT Trial)

Recruiting at 1 trial location

Overseen By Carolyn Paiz, BS

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas Health Science Center at San Antonio

Must be taking: Antipsychotics

Must not be taking: Antipsychotics

Disqualifiers: Caregiver unavailable, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two medications, pimavanserin and quetiapine, can assist individuals with psychosis (hallucinations or delusions) due to Lewy body disease (LBD), which includes Parkinson's disease and dementia with Lewy bodies. The goal is to determine which drug performs better in real-world settings. Individuals diagnosed with psychosis from these conditions who need to begin antipsychotic treatment might be suitable candidates. Participants should be open to starting either pimavanserin or quetiapine as their treatment. As a Phase 4 trial, this study involves treatments already approved by the FDA and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

If you are currently taking an antipsychotic medication, you will need to stop before joining this trial.

What is the safety track record for pimavanserin and quetiapine?

Research has shown that pimavanserin is generally safe for treating hallucinations and delusions in people with Parkinson's disease. In one study, 4.8% of patients taking pimavanserin experienced serious side effects, similar to those taking a placebo (a pill with no active medicine). Another review found that pimavanserin is safe and tolerable over the long term, although some people did not respond as well as expected.

Studies have also shown that quetiapine is well-tolerated. In a study involving people with Lewy Body Disease, quetiapine did not worsen Parkinson's symptoms. However, some common side effects include sleepiness, dizziness, dry mouth, and constipation. Both pimavanserin and quetiapine can cause some side effects, but they are considered safe options for managing psychosis in elderly patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for Lewy Body Disease because they offer new approaches to managing dementia-related psychosis. Pimavanserin is unique as it specifically targets serotonin receptors, which may help reduce hallucinations and delusions without the dopamine blockade commonly associated with other antipsychotics like haloperidol. This could mean fewer motor side effects for patients. On the other hand, Quetiapine is already used for conditions like schizophrenia and bipolar disorder and is known for its sedative properties, which might help manage agitation and insomnia in dementia patients. Both treatments provide alternative options that could potentially improve the quality of life for those affected by this challenging condition.

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

This trial will compare the effectiveness of pimavanserin and quetiapine in managing psychosis related to Lewy body disease. Studies have shown that pimavanserin reduces hallucinations and delusions in people with Parkinson's disease psychosis. It is approved for this use, indicating strong evidence of its effectiveness. Research also suggests that pimavanserin can help with psychosis related to dementia, including dementia with Lewy bodies. For quetiapine, 80-90% of patients with Parkinson's disease and dementia with Lewy bodies experienced a reduction in psychosis symptoms. One small study found that quetiapine was well tolerated and did not worsen Parkinson's symptoms. Both treatments have demonstrated effectiveness in managing psychosis in conditions related to Lewy body disease. ^{1 4 5 6 7}

Who Is on the Research Team?

Sarah Horn

Principal Investigator

University of Texas Health Science Center San Antonio

Are You a Good Fit for This Trial?

This trial is for individuals with hallucinations or delusions due to Parkinson's disease (PD) or dementia with Lewy bodies (DLB), who need to start antipsychotic treatment. Participants must be seen at the UT Health San Antonio neurology clinic and have a doctor willing to manage both Pimavanserin and Quetiapine treatments.

Inclusion Criteria

Clinical equipoise between quetiapine and pimavanserin must exist

My doctor is experienced in prescribing and managing quetiapine and pimavanserin.

Patients seen in the neurology clinic at UT Health San Antonio

Exclusion Criteria

Caregiver unavailable to complete NPI-Q

I cannot take certain medications due to health risks.

My doctor is not willing to manage my medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either quetiapine or pimavanserin to treat psychosis in Lewy body disease

6 months

Regular visits as per clinical practice

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pimavanserin
• Quetiapine

Trial Overview The study aims to compare the effectiveness of two antipsychotic medications, Pimavanserin and Quetiapine, in improving psychosis symptoms in patients with Lewy body disease over time when used in routine clinical practice.

How Is the Trial Designed?

Group I: pimavanserin Active Control 1 Intervention

Elderly patients with dementia-related psychosis will be treated with pimavanserin, an atypical antipsychotic indicated for treatment of hallucinations and delusions associated with Parkinson's disease.

Group II: quetiapine Active Control 1 Intervention

Elderly patients with dementia-related psychosis will be treated with quetiapine, an atypical antipsychotic indicated for the treeatment of: schizophrenia, bipolar I manic episodes and bipolar depressive episodes.

Pimavanserin is already approved in United States for the following indications:

Approved in United States as Nuplazid for:

• Hallucinations and delusions associated with Parkinson's disease psychosis

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Published Research Related to This Trial

A 75-year-old man with dementia with Lewy bodies experienced worsened cognitive and motor functions after being treated with olanzapine for psychosis, highlighting the risks of antipsychotic medications in this population.

Discontinuing olanzapine led to recovery, and re-initiating Pimavanserin effectively managed his hallucinations, suggesting that Pimavanserin may be a safer alternative for treating psychosis in patients with DLB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroleptic Sensitivity in Dementia with Lewy Body and Use of Pimavanserin in an Inpatient Setting: A Case Report. Abadir, A., Dalton, R., Zheng, W., et al.[2022]

In a case series of 4 male patients with dementia with Lewy bodies (DLB), pimavanserin was well-tolerated and led to significant improvements in psychosis symptoms, such as hallucinations and delusions, after other treatments failed.

All patients had previously tried cholinesterase inhibitors and traditional antipsychotics without success, highlighting pimavanserin's potential as an effective alternative for managing psychosis in DLB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin Treatment for Psychosis in Patients with Dementia with Lewy Bodies: A Case Series. Rothenberg, KG., McRae, SG., Dominguez-Colman, LM., et al.[2023]

Clozapine, a novel neuroleptic drug, has shown special efficacy in treating psychotic symptoms in patients with diffuse Lewy body disease, a condition characterized by severe neuropsychiatric symptoms.

This case highlights the potential of clozapine as a treatment option for managing the complex symptoms of diffuse Lewy body disease, which includes dementia, psychosis, depression, and parkinsonian features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clozapine use in diffuse Lewy body disease. Chacko, RC., Hurley, RA., Jankovic, J.[2013]

Clozapine is the most effective neuroleptic for treating psychotic symptoms in Parkinson's Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB), but its use is limited due to the risk of agranulocytosis and the need for regular blood monitoring.

Pimavanserin offers a promising alternative for treating Parkinson's Disease Psychosis (PDP) without worsening motor function, although more research is needed to confirm its efficacy and safety in DLB psychosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of psychosis in Parkinson's disease and dementia with Lewy Bodies: A review. Kyle, K., Bronstein, JM.[2021]

Pimavanserin, an antipsychotic approved for Parkinson's disease psychosis, effectively improved psychotic symptoms in a 75-year-old man with Lewy Body Dementia over a six-week period, without worsening his motor symptoms.

The medication works as a serotonin 2A inverse agonist, suggesting potential for use in other conditions presenting with psychosis, although current literature on off-label uses is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin Use in Lewy Body Dementia: A Case Report Demonstrating the Medication's Efficacy. Baker, M., Song, W., Fusick, A.[2023]

In a case review of a patient with Alzheimer's and Lewy body dementia, stopping risperidone led to serious psychiatric symptoms, highlighting the importance of careful medication management in dementia patients.

The healthcare team opted for quetiapine due to its short half-life and low anticholinergic effects, demonstrating a collaborative approach to resolving potential drug-related issues in a patient with complex needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medication review for dementia patients]. Jahns, KP., Kilimann, I., Ritter, CA., et al.[2012]

Lewy body dementia (DLB) is a common form of dementia characterized by cognitive fluctuations, visual hallucinations, and mild parkinsonism, affecting 20% to 34% of dementia cases, yet it is often underdiagnosed.

Quetiapine is highlighted as a promising treatment for psychotic symptoms in DLB, as it effectively reduces psychiatric manifestations without causing neuroleptic sensitivity or increasing extrapyramidal symptoms, unlike other atypical antipsychotics such as olanzapine and risperidone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lewy body dementia: the litmus test for neuroleptic sensitivity and extrapyramidal symptoms. Baskys, A.[2018]

Pimavanserin (PIM) treatment for Parkinson's Disease Psychosis (PDP) is associated with significantly lower rates of all-cause hospitalizations and psychiatric-related inpatient hospitalizations compared to quetiapine (QUE), suggesting it may be a safer option for managing PDP.

In a study of over 8,000 patients, those on PIM had a 22% reduction in all-cause hospitalizations and a 37% reduction in psychiatric-related hospitalizations, indicating its potential efficacy in reducing healthcare resource utilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients treated with pimavanserin or quetiapine for Parkinson's disease psychosis: analysis of health resource utilization patterns among Medicare beneficiaries. Rajagopalan, K., Rashid, N., Doshi, D.[2023]

In a study of nine patients with dementia with Lewy bodies, quetiapine treatment led to a positive response in five patients, showing over a 50% reduction in psychotic symptoms and aggressive behavior as measured by the Neuropsychiatric Inventory after 8 weeks.

However, three patients experienced side effects such as somnolence or orthostatic hypotension, leading to withdrawal from the treatment, indicating that while quetiapine may be beneficial for some, it also carries risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quetiapine treatment of psychotic symptoms and aggressive behavior in patients with dementia with Lewy bodies: a case series. Takahashi, H., Yoshida, K., Sugita, T., et al.[2022]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2034634

Trial of Pimavanserin in Dementia-Related Psychosis Pimavanserin has shown efficacy in patients with hallucinations and delusions associated with Parkinson's disease psychosis and is approved for ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10549935/

Pimavanserin Treatment for Psychosis in Patients with ... In a clinical trial of patients with Alzheimer disease (AD) and psychosis, there was a 6-month reduction in psychosis but not a 12-month reduction [15]. The ...

3. lbda.org lbda.org/new-research-supports-nuplazid-pimavanserin-use-in-parkinsons-disease-dementia/

New Research Supports Nuplazid (Pimavanserin) Use in ... The new label makes it clear that pimavanserin is FDA-approved for treatment of psychosis in Parkinson's disease dementia.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2590112522000147

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 concomitantly with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03325556

Relapse Prevention Study of Pimavanserin in Dementia- ... The purpose of this study is to evaluate the efficacy of pimavanserin compared to placebo in preventing relapse of psychotic symptoms in subjects with dementia ...

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

Long-term outcomes with pimavanserin for psychosis in ... A review of our real-world experience shows that pimavanserin is safe and tolerable, with a lower long-term response rate than reported in other publications.

7. lbda.org lbda.org/positive-results-for-the-harmony-clinical-trial-of-pimavanserin-in-dementia-related-psychosis/

Positive Results for the HARMONY Clinical Trial Serious adverse events were also low, 4.8% in the pimavanserin group and 3.6% in the placebo group. One death was reported in the open-label period and one ...