Recruiting

Pimavanserin vs. Quetiapine

Sponsor:

VA Office of Research and Development

Code:

NCT04373317

Conditions

Parkinson's Disease Psychosis

Eligibility Criteria

Sex: All

Age: 40+

Healthy Volunteers: Accepted

Interventions

Pimavanserin

Quetiapine

Study Details

Brief 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.

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).

Conditions

Parkinson's Disease Psychosis

Study ID

NCT04373317

Start date

Oct 24, 2022

Status verified date

Aug, 2026

Completion date

Aug 24, 2028

Anticipated

Primary completion date

Oct 24, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 40+

Healthy Volunteers: Accepted

Inclusion Criteria:

  • 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
  • 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

358 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Pimavanserin 34mg

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.

active comparator: Quetiapine

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

Interventions

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

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

Primary outcome measure

  • CGI-I Psychosis [ Time Frame: 8 Weeks ]

Central Contacts and Locations

Central contacts

Daniel Weintraub, MD

(215) 823-5800daniel.weintraub@va.gov

John E Duda, MD

(215) 823-5934john.duda@va.gov

Locations

VA Loma Linda Healthcare System, Loma Linda, CA

Recruiting

Loma Linda, California, United States, 92357-1000

Contacts

Dorothee Cole, MD

909-825-7084Dorothee.Cole@va.gov

Sonia Read

9098257084Sonia.Read@va.gov

VA Palo Alto Health Care System, Palo Alto, CA

Recruiting

Palo Alto, California, United States, 94304-1207

Contacts

Shannon Kilgore, MD

650-858-3999Shannon.Kilgore@va.gov

Cheyenne Murphy

6504935000Cheyenne.Murphy@va.gov

Rocky Mountain Regional VA Medical Center, Aurora, CO

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Jeanne Feuerstein, MD

720-723-6205Jeanne.Feuerstein@va.gov

Minneapolis VA Health Care System, Minneapolis, MN

Recruiting

Minneapolis, Minnesota, United States, 55417

Contacts

James Ashe, MD

612-725-2000James.Ashe@va.gov

Molly Carson

6127252000Molly.Carson@va.gov

Louis Stokes VA Medical Center, Cleveland, OH

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Peijun Chen

216-791-3800Peijun.Chen@va.gov

Aasef Shaikh

2167913800Aasef.Shaikh@va.gov

VA Portland Health Care System, Portland, OR

Recruiting

Portland, Oregon, United States, 97239

Contacts

Joel Mack, MD

503-220-8262Joel.Mack@va.gov

Michael Tanaka

5032208262Michael.Tanaka2@va.gov

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Recruiting

Philadelphia, Pennsylvania, United States, 19104-4551

Contacts

Daniel Weintraub, MD

(215) 823-5800daniel.weintraub@va.gov

Philadelphia MultiService Center, Philadelphia, PA

Recruiting

Philadelphia, Pennsylvania, United States, 19106

Contacts

James Morley, MD

215-823-5934James.Morley@va.gov

Philip Danquah

Philip.Danquah@va.gov

Michael E. DeBakey VA Medical Center, Houston, TX

Recruiting

Houston, Texas, United States, 77030

Contacts

Aliya Sarwar, MD

713-794-7841Aliya.Sarwar@va.gov

Priscilla Bigner

7137947939Priscilla.Bigner@va.gov

More Information

Sponsor

VA Office of Research and Development

Last update posted

Aug 19, 2026

Last verified

Aug, 2026

Keywords

  • Pimavanserin
  • Quetiapine

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-08-19.