Pimavanserin vs. Quetiapine for Treatment of Parkinson's Psychosis

Parkinson's Disease Psychosis Clinical Trial

— C-SAPP  

Official title:

CSP #2015 - Multicenter, Randomized, Double-blind Comparator Study of Antipsychotics Pimavanserin and Quetiapine for Parkinson''s Disease Psychosis (C-SAPP)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04373317
• Other study ID #: 2015
• Status: Recruiting
• Phase: Phase 4
• Start date: October 24, 2022
• Est. completion date: August 24, 2026

Study information

• Verified date: February 2024
• Source: VA Office of Research and Development
• Contact: Daniel Weintraub, MD
• Phone: (215) 823-5800
• Email: daniel.weintraub[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with Parkinson's disease (PD) sometimes experience symptoms affecting their movement, such as slowness, tremor, stiffness, and balance or walking problems. Many patients also have other symptoms not related to movement, called non-motor symptoms, which may affect one's mood or emotions, memory or thinking, or cause one to see or hear things that aren't real (hallucinations) or believe things that aren't true (delusions). Hallucinations or delusions, together called psychosis, occur in up to 60% of PD patients at some point in time. Parkinson's disease psychosis can sometimes be associated with decreased quality of life, increased nursing home placement, increased rate of death, and greater caregiver burden. There are approximately 50,000 Veterans with Parkinson's disease receiving care in the VA, and up to 30,000 (60%) of them will experience psychosis at some point in time.

Quetiapine is an antipsychotic drug approved by the Food and Drug Administration (FDA) that is the most commonly used medication to treat PD psychosis, but more studies are needed to determine if it works for this condition and is also well tolerated and safe. Pimavanserin is a newer antipsychotic drug approved by the Food and Drug Administration (FDA) specifically to treat PD psychosis, but more studies are needed to determine if it works and its safety.

The purpose of this research is to gather additional information on the safety and effectiveness of both Quetiapine and Pimavanserin. By doing this study, the investigators hope to learn which of these medications is the most effective course of treatment for people with PD psychosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 358
• Est. completion date: August 24, 2026
• Est. primary completion date: October 24, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years and older

Eligibility

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 1 month

• 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 in-person contact with the patient (at least 5 days per week, and at least 4 hours per day that is spent with patient)

• English-speaking

INFORMED OTHER

• Age 18 years or older

• Must have regular in-person contact with the patient (on average at least 5 days per week, and at least 4 hours per day that is spent with patient)

• 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 an antipsychotic, including pimavanserin in the past year, except quetiapine <50 mg/day which has been discontinued for at least 1 month prior to study randomization

• Deep brain stimulation (DBS) surgery occurring within 6 months prior or has had stimulator adjustments in the previous month

• History of a psychotic disorder prior to PD, including schizophrenia and bipolar disorder

• Suspected atypical parkinsonian disorder or dementia with Lewy bodies (DLB)

• Psychosis secondary to other toxic or metabolic disorder

• History of long QT syndrome

• Prolonged QTc [>450ms in men, >470ms in women] at screening

• History of ventricular arrhythmias, 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 prolongs the QTc interval

• Comorbid medical condition determined too severe by SI to allow participation in clinical trial

• Failure to tolerate quetiapine or pimavanserin previously

• Moderate to severe PD dementia (MoCA score <13)

• Currently enrolled in another therapeutic or interventional study

• Nursing home placement at screening or planned placement during the study

• Active suicidality

• Pregnant, or a female of child-bearing potential who is unwilling to use a reliable form of contraception

Related Conditions & MeSH terms

• Mental Disorders
• Parkinson Disease
• Parkinson's Disease Psychosis
• Psychotic Disorders

Intervention

Drug:
• Pimavanserin
Fixed-dose Pimavanserin - Pimavanserin is a new antipsychotic agent, and pure 5HT-2A inverse agonist, that was approved by the FDA recently (2016) for the treatment of PDP. It is the only FDA-approved medication for PDP, but is still not the first-line AP used in PD. All participants assigned to pimavanserin will receive the FDA-approved dose of 34 mg (equivalent to 40 mg pimavanserin tartrate) daily without titration up or down; however, because pimavanserin is blinded to quetiapine, participants will undergo sham titration based on tolerability (i.e., overall adverse event profile) and efficacy (i.e., improvement in severity of psychosis).
• Quetiapine
Flexible-dose Quetiapine - Quetiapine, which is a mixed serotonin and dopamine receptor antagonist, is by far the most commonly used AP for PDP. However, scientific evidence for the efficacy of quetiapine in PDP is almost non-existent as most of the studies were underpowered, had high drop-out rates, and possibly underdosed quetiapine. Quetiapine immediate and extended release will be titrated as shown: Baseline visit Quetiapine: 25 mg IR QHS, All participants must be up-titrated to 50 mg/day Pimavanserin: 34 mg QHS Week 1 call Quetiapine: 50 mg XR QHS, Up-titration to 50 mg Pimavanserin: 34 mg QHS Week 3 visit Quetiapine: 100 mg XR QHS, Up-titration as appropriate Pimavanserin: 34 mg QHS Week 5 visit Quetiapine: 150 mg XR QHS, Up- or down-titration as appropriate Pimavanserin: 34 mg QHS Week 6 call Quetiapine: 200 mg XR QHS, Up- or down-titration as appropriate Pimavanserin: 34 mg QHS

Locations

Country	Name	City	State
United States	New Mexico VA Health Care System, Albuquerque, NM	Albuquerque	New Mexico
United States	VA Ann Arbor Healthcare System, Ann Arbor, MI	Ann Arbor	Michigan
United States	Asheville VA Medical Center, Asheville, NC	Asheville	North Carolina
United States	Rocky Mountain Regional VA Medical Center, Aurora, CO	Aurora	Colorado
United States	Louis Stokes VA Medical Center, Cleveland, OH	Cleveland	Ohio
United States	North Florida/South Georgia Veterans Health System, Gainesville, FL	Gainesville	Florida
United States	Edward Hines Jr. VA Hospital, Hines, IL	Hines	Illinois
United States	Michael E. DeBakey VA Medical Center, Houston, TX	Houston	Texas
United States	Lexington VA Medical Center, Lexington, KY	Lexington	Kentucky
United States	VA Loma Linda Healthcare System, Loma Linda, CA	Loma Linda	California
United States	William S. Middleton Memorial Veterans Hospital, Madison, WI	Madison	Wisconsin
United States	Minneapolis VA Health Care System, Minneapolis, MN	Minneapolis	Minnesota
United States	Tennessee Valley Healthcare System Nashville Campus, Nashville, TN	Nashville	Tennessee
United States	VA Palo Alto Health Care System, Palo Alto, CA	Palo Alto	California
United States	Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA	Philadelphia	Pennsylvania
United States	Philadelphia MultiService Center, Philadelphia, PA	Philadelphia	Pennsylvania
United States	VA Portland Health Care System, Portland, OR	Portland	Oregon
United States	Hunter Holmes McGuire VA Medical Center, Richmond, VA	Richmond	Virginia
United States	St. Louis VA Medical Center John Cochran Division, St. Louis, MO	Saint Louis	Missouri
United States	South Texas Health Care System, San Antonio, TX	San Antonio	Texas
United States	San Francisco VA Medical Center, San Francisco, CA	San Francisco	California
United States	VA Puget Sound Health Care System Seattle Division, Seattle, WA	Seattle	Washington
United States	Syracuse VA Medical Center, Syracuse, NY	Syracuse	New York
United States	Southern Arizona VA Health Care System, Tucson, AZ	Tucson	Arizona
United States	VA Greater Los Angeles Healthcare System, West Los Angeles, CA	West Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CGI-I Psychosis	The Clinical Global Impressions (CGI) scale is a brief, well-established research rating tool used to quantify and track patient progress and treatment response over time. The CGI comprises two measures, one of which is Improvement (CGI-I) from the initiation of treatment. It is scored 1 to 7. The CGI-I is used to assess how much the patient's illness has improved or worsened relative to baseline when the intervention was started (1-Very much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse). The CGI-I can also be used to assess specific domains, including psychosis (this study's primary outcome) and parkinsonism (a secondary outcome). During the 8 weeks, the CGI-I (for psychosis, hereafter simply referred to as the CGI-I) will be administered to all participants at each in-person visit (3 weeks, 5 weeks, and 8 weeks following a CGI-I baseline interview) to assess clinical improvement in psychosis.	8 Weeks
Secondary	SAPS-PD	The primary assessment of change in psychosis severity is the score on the 9-item Parkinson's disease Scale for Assessment of Positive Symptoms (SAPS-PD). The SAPS-PD scale will assess positive symptoms, including hallucinations, delusions, bizarre behavior, and positive formal thought disorder. A clinical interview is used to evaluate the participant's symptoms. Items include: 1 Auditory Hallucinations; 2 Voices Conversing; 3 Somatic or Tactile Hallucinations; 4 Visual Hallucinations; 5 Global Rating of Severity of Hallucinations; 6 Persecutory Delusions; 7 Delusions of Jealousy; 8 Ideas and Delusions of Reference; and 9 Global Rating of Severity of Delusions. Each item is given a score ranging 0 to 5 (0-None, 1-Questionable, 2-Mild, 3-Moderate, 4-Marked, 5-Severe). During the 8 weeks, the SAPS-PD will be administered to all participants at each in-person visit (baseline, 3 weeks, 5 weeks, and 8 weeks) to assess symptoms of PDP and psychopharmacological response to treatment.	8 Weeks
Secondary	MDS-UPDRS III	The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination; MDS-UPDRS III) has 33 scores across 18 items (each score 0-4, range of total score 0-132, with higher scores indicating more severe motor symptoms) is completed by a trained rater during an examination of the patient, and is the most commonly-used assessment of parkinsonism in clinical trials. MDS-UPDRS III includes ratings for tremor, slowness (bradykinesia), stiffness (rigidity), and gait/balance. During the 8 weeks, the MDS-UPDRS III will be administered to all participants at each in-person visit (baseline, 3 weeks, 5 weeks, and 8 weeks).	8 Weeks
Secondary	Zarit Caregiver Burden Scale	The Zarit Burden Interview (ZBI) is a 22-item self-report inventory that examines burden associated with functional/behavioral impairments and the home care situation. It was developed to measure subjective burden among caregivers of adults with dementia. The items are worded subjectively, focusing on the affective response of the caregiver. Each question is scored on a 5-point Likert scale ranging from 0 to 4 (0-Never, 1-Rarely, 2-Sometimes, 3-Frequently, 4-Nearly always). The ZBI total score ranges from 0 (low burden) to 88 (high burden), the sum of the scores from all 22 questions. Interpretation of the total scores is: 1) 0-21 little or no burden; 2) 21-40 mild to moderate burden; 3) 41-60 moderate to severe burden; and 4) 61-88 severe burden. The ZBI will be administered to all participants' informed other at baseline and treatment phase visits of Weeks 5 and 8.	8 Weeks
Secondary	CGI-I Parkinsonism	The Clinical Global Impressions (CGI) scale is a brief, rating tool used to quantify and track patient progress and treatment response over time. It was developed to be used in clinical trials on mental health to provide an assessment of the clinician's view of the patient's global functioning over time with a study medication. The CGI comprises two measures, but the one to be used in this study is Improvement (CGI-I) from the st of treatment. It is scored from 1 to 7. The CGI-I is used to assess how much the patient's illness has improved or worsened relative to baseline when the intervention was started (1-Very much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse). During the 8 weeks, the CGI-I (for parkinsonism) will be administered to all participants at each in-person visit (3 weeks, 5 weeks, and 8 weeks following a CGI-I baseline interview) to assess improvement in parkinsonism.	8 Weeks