Comparing Antipsychotic Medications in LBD Over Time

Study Overview
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Brief Summary
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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).

Detailed Description
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Psychosis (hallucinations and delusions) is a common problem in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). PD is a common neurodegenerative disorder that causes movement, cognitive, and psychiatric symptoms. DLB is a similar disorder, though causes more severe cognitive and psychiatric problems. Psychosis is highly prevalent among people with PD and DLB, often manifesting as visual hallucinations or paranoid delusions. Up to 60% of people with PD will experience psychosis over the course of their disease. Psychosis is associated with increased mortality, caregiver burden, and poorer quality of life. More study is needed to determine the best way to treat psychosis in PD and DLB. Currently, both quetiapine and pimavanserin are used in clinical practice for psychosis in PD and DLB. However, few comparison studies have been done and it is unclear if one medication is superior to the other. This will be a clinical trial comparing quetiapine and pimavanserin among patients with psychosis due to PD or DLB requiring initiation of a medication. Patients will be randomized to quetiapine or pimavanserin and improvement in psychosis at 6 months will be compared between the groups.

Official Title
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A Pragmatic Randomized Trial Comparing Antipsychotics in Lewy Body Disease

Conditions
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Parkinson's Disease Psychosis, Dementia With Lewy Bodies

Intervention / Treatment
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* Drug: Pimavanserin
* Drug: Quetiapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients seen in the neurology clinic at UT Health San Antonio Diagnosed with psychosis due to PD or DLB Requiring initiation of an antipsychotic medication Clinical equipoise between quetiapine and pimavanserin must exist The prescribing provider must be comfortable prescribing and managing both quetiapine and pimavanserin Exclusion Criteria: Medical contraindication to either medication Caregiver unavailable to complete NPI-Q Currently taking an antipsychotic medication Prescribing provider unwilling to manage either medication
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: quetiapine<br>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. | Drug: Quetiapine<br>* Dosage choice and further medication management will be at the discretion of the treating clinician, per routine clinical practice.<br>* Other names: Seroquel;|
| Active Comparator: pimavanserin<br>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. | Drug: Pimavanserin<br>* Dosage choice and further medication management will be at the discretion of the treating clinician, per routine clinical practice.<br>* Other names: Nuplazid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychiatry Inventory Questionnaire (NPI-Q), Hallucinations + Delusions (H+D) | Change in the Hallucinations + Delusions sub-score of the neuropsychiatric inventory questionnaire. Each NPI-Q item is scored by severity (1-3), and distress to caregiver (0-5), then added together (range 0-8) with a higher score indicating greater severity. | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychiatry Inventory Questionnaire (NPI-Q) total score | Change in the total neuropsychiatric inventory questionnaire score, which includes 12 items, each scored from 0-8 with a higher score indicating more severe symptoms. | Baseline to 6 months | 
| Neuropsychiatry Inventory Questionnaire (NPI-Q) (anxiety) | Change in the neuropsychiatric inventory questionnaire item for anxiety, scored from 0-8 with a higher score indicating more severe anxiety. | Baseline to 6 months | 
| Neuropsychiatry Inventory Questionnaire (NPI-Q) (agitation) | Change in the neuropsychiatric inventory questionnaire for agitation, scored from 0-8 with a higher score indicating more severe agitation. | Baseline to 6 months | 
| Neuropsychiatry Inventory Questionnaire (NPI-Q) (nighttime behaviors) | Change in the neuropsychiatric inventory questionnaire for sleep disturbance, scored from 0-8 with a higher score indicating more severe sleep disturbances. | Baseline to 6 months | 
| Mortality | Number of subjects who survived until the 6 month study assessment visit | 6 months | 
| Time to discontinuation of per-protocol medication | Will examine whether participants continued the chosen medication until study completion or if they either discontinued the study medication or added the other study medication. | Baseline to 6 months | 
| MDS-UPDRS part 3 | Unified Parkinson's Disease Rating Scale, motor score. The motor examination scale consists of 33 items graded 0-4 points with an overall possible score of 0-132 points. A higher score indicates a higher burden of motor symptoms. | Baseline to 6 months | 
| CGIC, PGIC, CGI-C:CVR | Clinician, patient, and caregiver global impressions of change. Each is a single item assessment rated from 1 (very much improved) to 7 (very much worse). A higher score indicates worsening symptoms. | Baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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quetiapine, pimavanserin, psychosis, hallucinations, delusions