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

Trial Summary

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 evidence supports the effectiveness of the drug Pimavanserin for treating psychosis in Lewy Body Disease?

Pimavanserin has been shown to help improve psychotic symptoms in patients with Lewy Body Dementia without worsening motor symptoms, as demonstrated in case reports and its approved use for similar symptoms in Parkinson's disease. ^{1 2 3 4 5}

Is it safe to use antipsychotics like Pimavanserin and Quetiapine for Lewy Body Disease?

Pimavanserin and Quetiapine are considered safer options for treating psychosis in Lewy Body Disease compared to other antipsychotics, as they are less likely to worsen motor symptoms or cause serious side effects like neuroleptic sensitivity. Pimavanserin is FDA-approved for Parkinson's disease psychosis and has shown potential in Lewy Body Disease, while Quetiapine is noted for reducing psychiatric symptoms without increasing the risk of neuroleptic sensitivity. ^{1 4 5 6 7}

How is the drug Pimavanserin unique in treating Lewy Body Disease?

Pimavanserin is unique because it treats psychosis in Lewy Body Disease without worsening motor symptoms, unlike many other antipsychotics that can cause severe side effects in these patients. It works by targeting serotonin receptors instead of dopamine, making it a safer option for those with neuroleptic sensitivity. ^{1 4 5 8 9}

What is the purpose of this trial?

The primary objective of this study is to determine whether treatment with pimavanserin or quetiapine is associated with a greater improvement in psychosis when used in a routine clinical setting to treat hallucinations and/or delusions due to Parkinson's disease (PD) or dementia with Lewy bodies (DLB) - collectively referred to as Lewy body disease (LBD).

Research Team

Sarah Horn

Principal Investigator

University of Texas Health Science Center San Antonio

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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 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]

References

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

Pimavanserin Use in Lewy Body Dementia: A Case Report Demonstrating the Medication's Efficacy. [2023]

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

Quetiapine treatment of psychotic symptoms and aggressive behavior in patients with dementia with Lewy bodies: a case series. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Neuroleptic Sensitivity in Dementia with Lewy Body and Use of Pimavanserin in an Inpatient Setting: A Case Report. [2022]

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

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

6. Germany pubmed.ncbi.nlm.nih.gov

[Medication review for dementia patients]. [2012]

7. England 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. [2023]

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

Pimavanserin Treatment for Psychosis in Patients with Dementia with Lewy Bodies: A Case Series. [2023]

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

Clozapine use in diffuse Lewy body disease. [2013]