Parkinson's Disease PsychosisPhase 4C-SAPPNCT04373317
Pimavanserin vs. Quetiapine for Treatment of Parkinson's Psychosis
A Phase 4 study testing Pimavanserin and Quetiapine in people with Parkinson's Disease Psychosis, run by VA Office of Research and Development at 24 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 40 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson's Disease Psychosis
- What is being tested?
- Pimavanserin and Quetiapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 358 participants
- Where
- 24 sitesUnited States
- Study dates
- 24 Oct 2022to 24 Aug 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Veteran
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
24 sites in 1 country. Contact the study team or a site near you to ask about taking part.
24 sites in 1 country
United States24 sites, 9 recruiting
- Terminated
New Mexico VA Health Care System, Albuquerque, NM
Albuquerque, New Mexico, 87108-5153
- Terminated
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, Michigan, 48105-2303
- Terminated
Asheville VA Medical Center, Asheville, NC
Asheville, North Carolina, 28805-2576
- Recruiting
Rocky Mountain Regional VA Medical Center, Aurora, CO
Aurora, Colorado, 80045
Jeanne Feuerstein, MD, 720-723-6205, Jeanne.Feuerstein@va.gov
- Recruiting
Louis Stokes VA Medical Center, Cleveland, OH
Cleveland, Ohio, 44106
Peijun Chen, 216-791-3800 ext. 66804, Peijun.Chen@va.gov
Aasef Shaikh, 2167913800 ext. 65229, Aasef.Shaikh@va.gov
- Terminated
North Florida/South Georgia Veterans Health System, Gainesville, FL
Gainesville, Florida, 32608-1135
- Terminated
Edward Hines Jr. VA Hospital, Hines, IL
Hines, Illinois, 60141-3030
- Recruiting
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, Texas, 77030
Aliya Sarwar, MD, 713-794-7841, Aliya.Sarwar@va.gov
Priscilla Bigner, 7137947939, Priscilla.Bigner@va.gov
- Terminated
Lexington VA Medical Center, Lexington, KY
Lexington, Kentucky, 40502-2235
- Recruiting
VA Loma Linda Healthcare System, Loma Linda, CA
Loma Linda, California, 92357-1000
Dorothee Cole, MD, 909-825-7084 ext. 6049, Dorothee.Cole@va.gov
Sonia Read, 9098257084 ext. 2963, Sonia.Read@va.gov
- Recruiting
Minneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, 55417
James Ashe, MD, 612-725-2000 ext. 5538, James.Ashe@va.gov
Molly Carson, 6127252000 ext. 5203, Molly.Carson@va.gov
- Terminated
Tennessee Valley Healthcare System Nashville Campus, Nashville, TN
Nashville, Tennessee, 37212-2637
- Recruiting
VA Palo Alto Health Care System, Palo Alto, CA
Palo Alto, California, 94304-1207
Shannon Kilgore, MD, 650-858-3999, Shannon.Kilgore@va.gov
Cheyenne Murphy, 6504935000, Cheyenne.Murphy@va.gov
- Recruiting
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Philadelphia, Pennsylvania, 19104-4551
Daniel Weintraub, MD, (215) 823-5800 ext. 5934, daniel.weintraub@va.gov
Daniel Weintraub, MD
- Recruiting
Philadelphia MultiService Center, Philadelphia, PA
Philadelphia, Pennsylvania, 19106
James Morley, MD, 215-823-5934, James.Morley@va.gov
Philip Danquah, Philip.Danquah@va.gov
- Recruiting
VA Portland Health Care System, Portland, OR
Portland, Oregon, 97239
Joel Mack, MD, 503-220-8262 ext. 54521, Joel.Mack@va.gov
Michael Tanaka, 5032208262 ext. 57338, Michael.Tanaka2@va.gov
- Terminated
Hunter Holmes McGuire VA Medical Center, Richmond, VA
Richmond, Virginia, 23249-0001
- Terminated
South Texas Health Care System, San Antonio, TX
San Antonio, Texas, 78229-4404
- Terminated
San Francisco VA Medical Center, San Francisco, CA
San Francisco, California, 94121-1563
- Terminated
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, 98108-1532
- Terminated
St. Louis VA Medical Center John Cochran Division, St. Louis, MO
St Louis, Missouri, 63106-1621
- Terminated
Syracuse VA Medical Center, Syracuse, NY
Syracuse, New York, 13210-2716
- Terminated
Southern Arizona VA Health Care System, Tucson, AZ
Tucson, Arizona, 85723-0001
- Terminated
VA Greater Los Angeles Healthcare System, West Los Angeles, CA
West Los Angeles, California, 90073-1003
About this study
Official title: CSP #2015 - Multicenter, Randomized, Double-blind Comparator Study of Antipsychotics Pimavanserin and Quetiapine for Parkinson''s Disease Psychosis (C-SAPP)
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.
Read more
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.
Enrollment is open to Veterans nationwide, see your VA provider about the possibility of being referred to one of the study's Hub sites. This can be done through contact from your provider to the study's NSC (Tamara Boney at 267-303-9829).
Read the detailed description
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.
- Conditions
- Parkinson's Disease Psychosis
- Being tested
- Pimavanserin, Quetiapine
- Keywords
- Pimavanserin, Quetiapine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PimavanserinDrug
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).
QuetiapineDrug
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
Week 1 call Quetiapine: 50 mg XR QHS, Up-titration to 50 mg
Week 3 visit Quetiapine: 100 mg XR QHS, Up-titration as appropriate
Week 5 visit Quetiapine: 150 mg XR QHS, Up- or down-titration as appropriate
Week 6 call Quetiapine: 200 mg XR QHS, Up- or down-titration as appropriate
| Study group | Role | What they receive |
|---|---|---|
| Pimavanserin 34mg | Active comparator | Participants assigned to pimavanserin will receive 34 milligrams (mg) (equivalent to 40 mg pimavanserin tartrate) daily without titration; however, because pimavanserin is blinded to quetiapine, participants will undergo sham titration based on tolerability. Receives: Drug: Pimavanserin |
| Quetiapine | Active comparator | Participants assigned to Quetiapine will be titrated from 25 milligrams (mg)/day to a maximum of 200mg/day based on tolerability. During the 8-week treatment phase, there is a maximum of 6 weeks for titration.
Titration Schedule
Visit/call Quetiapine Dose (Flexible)Quetiapine Notes Baseline visit (Visit 00)25 mg IR QHSAll participants must be up-titrated to at least 50 mg/day at week 1 Week 1 call (Visit 01)50 mg XR QHS Up-titration Week 3 visit (Visit 03)100 mg XR QHS (requiring two 50-mg quetiapine XR capsules)Up- or down-titration as appropriate based on psychosis symptoms and tolerability Week 5 visit (Visit 05)150 mg quetiapine XR QHS Up- or down-titration as appropriate based on psychosis symptoms and tolerability Week 6 call (Visit 06)200 mg quetiapine XR QHS Up- or down-titration as appropriate based on psychosis symptoms and tolerability Receives: Drug: Quetiapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 3 weeks, 5 weeks, and 8 weeks following a CGI-I baseline interview to assess clinical improvement in psychosis.
Measured: 8 Weeks
Secondary outcomes (4)
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 baseline, 3 weeks, 5 weeks, and 8 weeks to assess symptoms of PDP and psychopharmacological response to treatment.
Measured: 8 Weeks
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. The MDS-UPDRS III will be administered to all participants at baseline and 8 weeks.
Measured: 8 Weeks
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). The CGI-I (for parkinsonism) will be administered to all participants at 8 weeks following a CGI-I baseline interview to assess improvement in parkinsonism.
Measured: 8 Weeks
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.
Measured: 8 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2020
- Study start24 Oct 2022
- Primary completion24 Oct 2027 (estimated)
- Study completion24 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's Disease PsychosisStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two active treatments will be administered in this RCT, with 1:1 treatment assignment to either quetiapine or pimavanserin. Both active treatments are FDA-approved antipsychotics.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 358 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Daniel Weintraub, MD, Study chair, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04373317
- Sponsor's protocol ID
- 2015
- Acronym
- C-SAPP
- Status last verified
- Aug 2026
- First submitted
- 29 Apr 2020
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CSP #2015 - Multicenter, Randomized, Double-blind Comparator Study of Antipsychotics Pimavanserin and Quetiapine for Parkinson''s Disease Psychosis (C-SAPP)
- ClinicalTrials.gov ID
- NCT04373317
- Acronym / sponsor ID
- C-SAPP / 2015
- Conditions
- Parkinson's Disease Psychosis
- Keywords
- Pimavanserin, Quetiapine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 358 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 24 Oct 2022 (actual)
- Primary completion
- 24 Oct 2027 (estimated)
- Study completion
- 24 Aug 2028 (estimated)
- First posted
- 4 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Enrollment is open to Veterans nationwide, see your VA provider about the possibility of being referred to one of the study's Hub sites. This can be done through contact from your provider to the study's NSC (Tamara Boney at 267-303-9829).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Two active treatments will be administered in this RCT, with 1:1 treatment assignment to either quetiapine or pimavanserin. Both active treatments are FDA-approved antipsychotics.
| Arm | Type | Receives |
|---|---|---|
| Pimavanserin 34mg | Active comparator | Drug: PimavanserinParticipants assigned to pimavanserin will receive 34 milligrams (mg) (equivalent to 40 mg pimavanserin tartrate) daily without titration; however, because pimavanserin is blinded to quetiapine, participants will undergo sham titration based on tolerability. |
| Quetiapine | Active comparator | Drug: QuetiapineParticipants assigned to Quetiapine will be titrated from 25 milligrams (mg)/day to a maximum of 200mg/day based on tolerability. During the 8-week treatment phase, there is a maximum of 6 weeks for titration. Titration Schedule Visit/call Quetiapine Dose (Flexible)Quetiapine Notes Baseline visit (Visit 00)25 mg IR QHSAll participants must be up-titrated to at least 50 mg/day at week 1 Week 1 call (Visit 01)50 mg XR QHS Up-titration Week 3 visit (Visit 03)100 mg XR QHS (requiring two 50-mg quetiapine XR capsules)Up- or down-titration as appropriate based on psychosis symptoms and tolerability Week 5 visit (Visit 05)150 mg quetiapine XR QHS Up- or down-titration as appropriate based on psychosis symptoms and tolerability Week 6 call (Visit 06)200 mg quetiapine XR QHS Up- or down-titration as appropriate based on psychosis symptoms and tolerability |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Veteran
- 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
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PimavanserinFixed-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). | Drug | Pimavanserin 34mg |
| QuetiapineFlexible-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 Week 1 call Quetiapine: 50 mg XR QHS, Up-titration to 50 mg Week 3 visit Quetiapine: 100 mg XR QHS, Up-titration as appropriate Week 5 visit Quetiapine: 150 mg XR QHS, Up- or down-titration as appropriate Week 6 call Quetiapine: 200 mg XR QHS, Up- or down-titration as appropriate | Drug | Quetiapine |
Primary outcome
CGI-I Psychosis
Time frame: 8 Weeks
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 3 weeks, 5 weeks, and 8 weeks following a CGI-I baseline interview to assess clinical improvement in psychosis.
4 secondary outcomes
SAPS-PD
Time frame: 8 Weeks
MDS-UPDRS III
Time frame: 8 Weeks
CGI-I Parkinsonism
Time frame: 8 Weeks
Zarit Caregiver Burden Scale
Time frame: 8 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Individual participant dataSharing planned: No
Related trials for Parkinson's Disease Psychosis
Active, not recruitingPhase 2
Clinical Trial Evaluating the Efficacy and Safety of AGB101 for Treatment of Parkinson's Disease Related Psychosis
Parkinson Disease Psychosis
Recruiting
Ultra-High Resolution PET in Aging, Neurodegeneration and Psychotic Disorders
Alzheimer Dementia (AD), ALS - Amyotrophic Lateral Sclerosis
RecruitingPhase 4
Comparing Antipsychotic Medications in LBD Over Time
Parkinson's Disease Psychosis, Dementia With Lewy Bodies
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel Weintraub, MD study chair
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pimavanserin and Quetiapine in people with Parkinson's Disease Psychosis, run by VA Office of Research and Development at 24 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daniel Weintraub, MD ((215) 823-5800 ext. 5934, daniel.weintraub@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CGI-I Psychosis (time frame: 8 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.