Adalimumab for REM Sleep Behavior Disorder

(PRISMS Trial)

Overseen By Deanna Sgambato, DMS, PA-C

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Anti-Parkinson, Cognitive enhancers, Antipsychotics, Immunosuppressants

Disqualifiers: Neurologic disorders, Autoimmune disease, Infections, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 96 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adalimumab, a medication, can reduce or halt the progression of brain issues related to REM Sleep Behavior Disorder (RBD). RBD causes individuals to physically act out dreams, sometimes resulting in injury. Participants will receive either adalimumab or a placebo (a harmless pill resembling the real medication) every two weeks for up to two years. The trial seeks individuals diagnosed with idiopathic RBD who experience dream enactment behavior during sleep. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

Yes, you may need to stop certain medications to join the trial. The trial excludes participants taking specific medications like anti-Parkinson agents, cognitive enhancers, stimulants, antipsychotics, and certain antidepressants unless their dose has been stable for at least 90 days.

Is there any evidence suggesting that adalimumab is likely to be safe for humans?

Research has shown that the FDA has already approved adalimumab for other conditions, suggesting it is somewhat safe. Studies have found that people with rheumatoid arthritis (RA) generally tolerate adalimumab well. It has been used to reduce disease activity and improve sleep issues in these patients. Like any medication, it can have side effects, but its use in other conditions offers some reassurance about its safety. However, this trial specifically tests adalimumab for REM Sleep Behavior Disorder, so results might differ. Discuss any concerns with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for RBD?

Unlike the standard treatments for REM Sleep Behavior Disorder, which often include medications like clonazepam or melatonin, Adalimumab offers a novel approach. Researchers are excited because Adalimumab, typically used for inflammatory conditions, targets specific immune pathways that might be involved in the disorder's underlying mechanisms. This could lead to a more targeted therapy, potentially reducing symptoms more effectively and with fewer side effects. Additionally, Adalimumab's bi-weekly administration could be more convenient for some patients compared to daily medications.

What evidence suggests that adalimumab might be an effective treatment for REM Sleep Behavior Disorder?

Studies have shown that adalimumab can improve sleep problems and reduce symptoms in conditions like rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Research also suggests it might help prevent the worsening of certain brain diseases linked to REM Sleep Behavior Disorder (RBD). In this trial, one group of participants will receive adalimumab every two weeks for up to two years to evaluate its effects on RBD. The treatment may work by affecting the immune system to slow or stop the disease. Early findings are promising, but more data is needed specifically for RBD. ^{1 2 4 5 6}

Who Is on the Research Team?

Jesse Cedarbaum, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals with idiopathic REM Sleep Behavior Disorder, who may be at risk of developing synucleinopathies like Parkinson's disease. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study.

Inclusion Criteria

MoCA score at screening and baseline >23

Able to understand the study requirements and provide written informed consent

I have been diagnosed with REM sleep behavior disorder.

Exclusion Criteria

MRI evidence of more than three lacunar infarcts, territorial infarct, or deep white matter lesions corresponding to a Fazekas score of 3

Participation in other interventional clinical trials or treatment with investigational drugs within 30 days prior to the first Screening visit

History of drug or alcohol abuse within the last 5 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

12 weeks

Treatment

Participants receive adalimumab or placebo every 2 weeks for up to 2 years

96 weeks

Visits at 4, 12, 26 weeks, and then every 26 weeks

Follow-up

A safety follow-up visit occurs 70 days after the last dose of study treatment

10 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adalimumab

Trial Overview The study is testing whether adalimumab can slow or prevent neurodegeneration associated with synucleinopathies in RBD patients. It's a phase 2 trial comparing adalimumab against a placebo, using PET imaging to measure changes in brain patterns related to Parkinson's disease.

How Is the Trial Designed?

Group I: Adalimumab Experimental Treatment 1 Intervention

Participants in this arm will receive Adalimumab every 2 weeks for up to 2 years

Group II: Placebo Placebo Group 1 Intervention

Participants in this arm will receive matching placebo every 2 weeks for up to 2 years

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

The Marcus Foundation

Collaborator

Trials

19

Recruited

2,200+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06996652

NCT06996652 | An Exploratory Study of the Potential for ... This is a phase 2 study to assess the ability of adalimumab as compared to placebo to reduce or prevent progression of synuclein-related neurodegeneration ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7534071/

Real-world evidence of the impact of adalimumab on work ... Adalimumab improves work productivity and sleep problems while lowering disease activity in patients with moderate to severe RA, PsA, and AS managed in real- ...

3. mdsabstracts.org mdsabstracts.org/abstract/the-potential-for-rational-immune-system-manipulation-to-prevent-emergence-of-synucleinopathy-manifestations-in-persons-with-rem-sleep-behavior-disorder-rbd/

The Potential for Rational Immune System Manipulation to ... The Potential for Rational Immune System Manipulation to Prevent Emergence of Synucleinopathy Manifestations in Persons with REM Sleep Behavior Disorder (RBD).

4. withpower.com withpower.com/trial/phase-2-rem-sleep-behavior-disorder-8-2025-12309

Adalimumab for REM Sleep Behavior Disorder (PRISMS ... This is a phase 2 study to assess the ability of adalimumab as compared to placebo to reduce or prevent progression of synuclein-related neurodegeneration ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7735522/

Clinical Trials in REM Sleep Behavior Disorder Clonazepam reduces the frequency of unpleasant dreams and decreasing violent dream enactment behavior [7 8], with complete resolution of symptoms observed in ...

6. medicine.yale.edu medicine.yale.edu/news-article/yale-school-of-medicine-receives-grant-from-the-marcus-foundation-to-treat-parkinsons-disease/

Yale School of Medicine Receives Grant From The Marcus ... This landmark gift from The Marcus Foundation will fund their clinical trial in people with RBD using Humira to assess whether anti-TNF ...