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Pimavanserin vs. Quetiapine for Treatment of Parkinson's Psychosis

NCT04373317 · VA Office of Research and Development
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Official title
CSP #2015 - Multicenter, Randomized, Double-blind Comparator Study of Antipsychotics Pimavanserin and Quetiapine for Parkinson''s Disease Psychosis (C-SAPP)
About this study
CSP #2015 - C-SAPP is a randomized, intent-to-treat, double-blind, two-arm, parallel design, multicenter comparator study. A total of up to approximately 24 Department of Veterans Affairs Medical Centers (VAMCs) will be invited to participate in the study. Veterans age 40 years and older with PD and symptoms of psychosis will be pre-screened for enrollment (consent) using established inclusion/exclusion criteria. Enrolled participants meeting eligibility will be randomized in a blinded fashion to one of two arms (fixed-dose pimavanserin or flexible-dose quetiapine), stratified by cognitive impairment \[per the Montreal Cognitive Assessment (MoCA)\]. Assessments will be collected at multiple time points - baseline, week 3, week 5, and at week 8 after randomization. Assessments of psychosis (CGI-I psychosis), PDP symptoms (SAPS-PD), and nighttime sleep/daytime sleepiness \[per Scales for Outcomes in PD-Sleep Scale nighttime subscale (SCOPA-S NS)/Epworth Sleepiness Scale (ESS)\] will be completed at each in-person visit, while caregiver burden (ZBI), functioning and well-being \[per the Parkinson's Disease Questionnaire-8 (PDQ-8)\] will be assessed at baseline and treatment visits of weeks 5 and 8, parkinsonism (CGI-I parkinsonism) and motor abilities (MDS-UPDRS III) at baseline and week 8, and cognition (MoCA) at screening and week 8. Additional contact by phone/video will occur at weeks 1 and 6. PD medications and side-effects will also be collected. SAEs, and AEs using the Treatment Emergent Symptom Scale (TESS) for guidance, will be continuously monitored at each participant contact (in-person and phone/video). A quality by design (QbD) approach was utilized focusing on its key principles to help prospectively identify important errors that could jeopardize the reliability of the data and safety of study participants.
Eligibility criteria
Inclusion Criteria: * Veteran * Age 40 years or older * Diagnosis of Parkinson's Disease consistent with UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria * Psychosis \[with Neuropsychiatric Inventory (NPI) hallucinations (B) or delusions (A) score 4 or greater\] * Stable dose of PD medications for at least 2 weeks * If on an acetylcholinesterase inhibitor (AChEI) initially prescribed at least 3 months prior and stable dose (no dose or medication change) for past month * Informed other must provide informed consent and agree to attend all study visits. The informed other must be at least 18 years of age and have regular contact with the patient (on average at least 4 days per week and at least 2 hours per day, or at least 3 days per week and at least 4 hours per day, that is with patient) via in-person, video, or telephone * English-speaking INFORMED OTHER * Age 18 years or older * Must have regular contact with the patient (on average at least 4 days per week, and at least 2 hours per day, or at least 3 days per week and at least 4 hours pr day, that is with patient) via in-person, video, or telephone * Agree to attend all study visits * Be able to provide informed consent * English-speaking Exclusion Criteria: * Psychosis symptoms severe enough to preclude enrollment in a clinical trial and require prompt clinical care instead * Treatment with quetiapine \>50 mg/day or pimavanserin in the past 3 months, or quetiapine 50 mg/day or another antipsychotic in the past week prior to study randomization * Deep brain stimulation (DBS) surgery within 3 months or has had stimulator adjustments in the previous 2 weeks * History of a psychotic disorder prior to PD, including bipolar disorder, schizophrenia, schizoaffective disorder, and major depressive disorder with psychotic features, if it is thought to be the cause of the current psychosis symptoms * Suspected atypical parkinsonian disorder or dementia with Lewy bodies (DLB) * Psychosis secondary to other toxic or metabolic disorder * History of long QT syndrome * Documented chart evidence indicating persistent hypoglycemia, hypokalemia, hypomagnesemia that would put patient at increased risk for QTc prolongation. * History of ventricular arrhythmias, except when treated with an implantable cardioverter defibrillator (ICD) or pacemaker, or untreated or unstable atrial fibrillation/flutter * Currently taking medications that are moderate or strong CYP3A4 inducers or strong CYP3A4 inhibitors * Concomitant use of drugs that prolong the QTc interval with a known risk of Torsades de Pointes * Comorbid medical condition determined too severe by Site Investigator to allow participation in clinical trial * Failure to tolerate quetiapine or pimavanserin previously * Severe cognitive impairment (MoCA score \<5) * Nursing home placement at screening or planned placement during the study, unless approved by study Co-Chairs. Approval will depend upon nursing facility agreement to receive, return, and administer medications or allow participant to self-administer study medications; appropriate IO availability; and transportation availability for study visits. * Currently enrolled in another therapeutic or interventional study * Pregnant, or a female of child-bearing potential who is unwilling to use a reliable form of contraception
Study design
Enrollment target: 358 participants
Allocation: randomized
Masking: triple
Age groups: adult, older_adult
Timeline
Starts: 2022-10-24
Estimated completion: 2027-08-24
Last updated: 2025-08-28
Interventions
Drug: PimavanserinDrug: Quetiapine
Primary outcomes
  • CGI-I Psychosis (8 Weeks)
Sponsor
VA Office of Research and Development · fed
Contacts & investigators
ContactDaniel Weintraub, MD · contact · daniel.weintraub@va.gov · (215) 823-5800
ContactJohn E Duda, MD · contact · john.duda@va.gov · (215) 823-5934
InvestigatorDaniel Weintraub, MD · study_chair, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
All locations (24)
Southern Arizona VA Health Care System, Tucson, AZTerminated
Tucson, Arizona, United States
VA Loma Linda Healthcare System, Loma Linda, CARecruiting
Loma Linda, California, United States
VA Palo Alto Health Care System, Palo Alto, CARecruiting
Palo Alto, California, United States
San Francisco VA Medical Center, San Francisco, CAActive Not Recruiting
San Francisco, California, United States
VA Greater Los Angeles Healthcare System, West Los Angeles, CATerminated
West Los Angeles, California, United States
Rocky Mountain Regional VA Medical Center, Aurora, CORecruiting
Aurora, Colorado, United States
North Florida/South Georgia Veterans Health System, Gainesville, FLActive Not Recruiting
Gainesville, Florida, United States
Edward Hines Jr. VA Hospital, Hines, ILActive Not Recruiting
Hines, Illinois, United States
Lexington VA Medical Center, Lexington, KYTerminated
Lexington, Kentucky, United States
VA Ann Arbor Healthcare System, Ann Arbor, MIActive Not Recruiting
Ann Arbor, Michigan, United States
Minneapolis VA Health Care System, Minneapolis, MNRecruiting
Minneapolis, Minnesota, United States
St. Louis VA Medical Center John Cochran Division, St. Louis, MOActive Not Recruiting
St Louis, Missouri, United States
New Mexico VA Health Care System, Albuquerque, NMTerminated
Albuquerque, New Mexico, United States
Syracuse VA Medical Center, Syracuse, NYTerminated
Syracuse, New York, United States
Asheville VA Medical Center, Asheville, NCTerminated
Asheville, North Carolina, United States
Louis Stokes VA Medical Center, Cleveland, OHRecruiting
Cleveland, Ohio, United States
VA Portland Health Care System, Portland, ORRecruiting
Portland, Oregon, United States
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PARecruiting
Philadelphia, Pennsylvania, United States
Philadelphia MultiService Center, Philadelphia, PARecruiting
Philadelphia, Pennsylvania, United States
Tennessee Valley Healthcare System Nashville Campus, Nashville, TNTerminated
Nashville, Tennessee, United States
Michael E. DeBakey VA Medical Center, Houston, TXRecruiting
Houston, Texas, United States
South Texas Health Care System, San Antonio, TXTerminated
San Antonio, Texas, United States
Hunter Holmes McGuire VA Medical Center, Richmond, VATerminated
Richmond, Virginia, United States
VA Puget Sound Health Care System Seattle Division, Seattle, WAActive Not Recruiting
Seattle, Washington, United States
Pimavanserin vs. Quetiapine for Treatment of Parkinson's Psychosis · TrialPath