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REM Sleep Behavior DisorderPhase 2PRISMSNCT06996652

An Exploratory Study of the Potential for Rational Immune System Manipulation to Prevent Emergence of Synucleinopathy Manifestations in Persons With REM Sleep Behavior Disorder (RBD)

A Phase 2 study testing Adalimumab in people with REM Sleep Behavior Disorder, run by Yale University at 19 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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 in persons with idiopathic REM Sleep Behavior Disorder (RBD). Read more about this study

Who is it for?
Ages 50 to 80 years
Conditions the study is for
REM Sleep Behavior Disorder
What is being tested?
Adalimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
108 participants
Where
19 sitesin 2 countries
Study dates
17 Aug 2026to 1 Jan 2030
Phase
Phase 2
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 50 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males, or females who are either
  • post-menopausal or otherwise not of child-bearing potential, defined as either 1) having had no menses for 12 or months without an alternative medical cause or explanation or 2) having undergone a surgical procedure (hysterectomy, bilateral tubal ligation) that prevents conception, or
  • practicing adequate contraception. Female participants of childbearing potential must practice at least 1 protocol-specified method of birth control, that is effective from 30 days before baseline (or earlier) through at least 150 days after the last dose of the study drug. Female participants of non-childbearing potential do not need to use birth control.
  • women of childbearing potential must have a negative urine pregnancy test prior to enrollment, and agree to undergo a pregnancy test at each study visit. Women with a positive pregnancy test at screening or at any subsequent study visit will be withdrawn from the study.
  • Diagnosis of idiopathic REM Sleep Behavior Disorder (RBD) based upon:
  • History of Dream Enactment Behavior during sleep and
Show all 15Show fewer
  • Evidence of REM sleep without muscle atonia based upon polysomnogram obtained in a qualified sleep laboratory, consistent with ICSD-3 Diagnostic Criteria for RBD
  • Hyposmia, defined as score < 15th percentile for age-and gender-specific normal values
  • Not diagnosed with motor Parkinson's Disease or Lewy Body Dementia
  • Have a MoCA score at screening and baseline ≥23
  • Able to speak, read and write fluently in the official language of the site's geographical region
  • Participant must be willing and able to attend all study visits as required by the study protocol
  • Participant must have a study partner who is in regular contact with the subject and can accompany the subject to clinic visits and report on subject's functional status
  • Participant must be able to self-inject study drug regularly or have a study partner who is available, willing and able to do so
  • Participant must be able to understand the study requirements and provide written informed consent

Who cannot join

  • Women who are pregnant, planning to become pregnant, or currently breastfeeding
  • Alternative explanation or etiology for the presence of RBD (e.g. narcolepsy)
  • Other than RBD, neurologic or medical disorder which may impair cognition including: head trauma, seizure disorder, neurodegenerative disease, hydrocephalus, cerebral/spinal hematoma, inflammatory disease, CNS infection (e.g., encephalitis or meningitis), neoplasm, toxic exposure, metabolic disorder (including hypoxic or hypoglycemic episodes), or endocrine disorder, or any significant medical conditions that, in the opinion of the investigator, would prohibit their participation in the study.
  • As assessed by the central reader, MRI evidence of (a) more than three lacunar infarcts, (b) territorial infarct or macroscopic hemorrhage, or (c) deep white matter lesions corresponding to a Fazekas score of 3
  • Any contra-indication to undergo MRI, as judged by local PI or radiologist, including but not limited to presence of pacemaker, aneurysm clips, artificial heart valves, ear implants, ventriculoperitoneal shunt, foreign metal objects in the eyes, skin or body or any other circumstance which would contra-indicate an MRI scan or impair MRI image quality, or history of claustrophobia or of not tolerating MRI scanning procedures
  • History or active presence of any of the following neurological, psychiatric or medical conditions:
Show all 40Show fewer
  • Large vessel stroke
  • Peripheral or CNS demyelinating disease
  • Chronic and/or recurrent fungal, bacterial or opportunistic infections
  • Myocardial infarction or unstable angina within the previous 12 months
  • Clinically relevant or significant ECG abnormalities, including ECG with QT interval corrected for heart rate using Fridericia's formula (QT interval corrected for heart rate using Fridericia's formula) > 450 msec (males) or > 470 msec (females).
  • Congestive heart failure, NYHA Class 3 or 4
  • Autoimmune disease (e.g., Systemic Lupus Erythematosis (SLE), or symptoms suggestive of a lupus-like syndrome, multiple sclerosis, rheumatoid arthritis, Type 1 diabetes mellitus, inflammatory bowel disease, psoriasis, etc.)
  • Immunocompromised systemically due to continuing effects of immune suppressing medication
  • Current or previous hepatitis B infection (defined as positive test for hepatitis B surface antigen (HbSAg) and/or hepatitis B core antibody (anti-HBc).
  • Participants with immunity to hepatitis B (if due to natural infection defined as negative HBsAg, positive hepatitis B antibody (anti-HBs) and positive anti-HBc; if due to vaccination defined as negative HBsAg, negative anti-HBc and positive anti-HBs are eligible to participate in the study
  • For patients with resolved HBV infection, if anti-HBc negative, HBV DNA testing is needed prior to initiating study drug j. History or positive test at Screening for hepatitis C virus antibody (anti-HCV) in the absence of treatment resulting in cure k. History or positive test at Screening for human immunodeficiency virus (HIV) l. History of untreated or incompletely treated tuberculosis or a positive tuberculosis IGRA test.
  • History of malignancy other than successfully treated, non-metastatic cutaneous squamous or basal cell carcinoma or localized carcinoma in situ of the cervix n. Major depressive episode requiring initiation of medication or hospitalization within the previous 90 days o. Seated blood pressure > 150/90 on 3 separate determinations p. Presence of hallucinations or delusions q. Psychiatric disorder (schizophrenia, schizoaffective disorder, etc.) associated with psychosis r. Active infection(s) requiring treatment with intravenous anti-infectives within 30 days, or oral/intramuscular anti-infectives within 14 days prior to baseline s. Major surgery within 12 weeks of screening t. Blood donation of 1 unit or more within 8 weeks prior to the first dose of study medication
  • Any of the following laboratory abnormalities at Screening
  • Screening values for hemoglobin < 12 g/d for men or < 11 g/dL for women or other clinically significant hematological abnormality
  • Any serum chemistry value (e.g., AST, ALT, alkaline phosphatase, CK, total bilirubin etc. > 2x the upper limit of normal on 2 successive determinations less than 2 weeks apart
  • Serum creatinine above the ULN or eGFR < 60 mL/min/1.73 m2
  • Platelet count, INR, PT or PTT not within the normal range or other risk for increased or uncontrolled bleeding
  • Any other significant medical conditions that, in the opinion of the investigator, would prohibit participation in the study, including inability to tolerate the MRI scan
  • For participants agreeing to lumbar puncture: Presence of contra-indication to lumbar puncture as judged by local PI (e.g., known X-ray or other evidence of significant lumbar spine abnormalities or history of lumbar surgery with sequalae that would interfere with or pose risks from the procedure; platelet count below 50,000 cells/mL; need for anticoagulant or antiplatelet medications other than aspirin at a dose of < 100 mg/day or clopidogrel (see item 10 (g) below))
  • Taking any of the following medications:
  • Symptomatic anti-Parkinson agents, including but not limited to levodopa-containing preparations, dopamine agonists, monoamine oxidase inhibitors, amantadine, and adenosine receptor antagonists taken any time prior to the screening visit
  • Cognitive enhancing agents, including but not limited to acetylcholinesterase inhibitors and memantine taken any time prior to the screening visit
  • Stimulant medications, including but not limited to lisdexamphetamine, dextroamphetamine/amphetamine (Adderall) and methylphenidate taken at any time prior to the screening visit
  • Antipsychotic agents, including pimavanserin
  • Antidepressant medications whose dose has not been stable for at least 90 days
  • Use of any of the following medications within 12 months prior to Screening: Immunosuppressant medications, including chronic corticosteroids, anakinra and abatacept
  • Any previous use of injected or infused antibody therapies, including but not limited antibodies directed against TNF, anti-IL-6, natalizumab, rituximab, conventional or targeted DMARD agents
  • For participants agreeing to undergo lumbar puncture: Anticoagulant or anti-platelet medications including warfarin, heparinoids and direct coagulation factor inhibitors (e.g., apixaban, dabigatran, rivaroxaban) within 90 days of the planned first dose of study drug; either aspirin at a dose of <¬ 100 mg/day or clopidogrel at a dose of 75 mg/day, but use of both in combination is permitted.
  • Received any live vaccine, with the exception of non-replicating live viral vaccines such as Jynneos vaccine, within 30 days prior to the first dose of study drug, or expected need of live vaccination during study participation including at least 70 days after the last dose of study drug.
  • History of an allergic reaction or significant sensitivity to adalimumab or constituents of the study drug (and its excipients) and/or other products in the same class
  • Participation in any other interventional clinical trial, or treatment with any investigational drug or investigational use of an approved therapy within 30 days (or 5 half-lives of such agent) prior to the first Screening visit.
  • History of drug or alcohol abuse within the last 5 years (including cannabis use disorder)
  • Positive urine drug test at screening
  • Unwillingness or inability to comply with study requirements, including self-administration of study medication, or history of noncompliance in prior clinical trials

Trial locations and contacts

19 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Erika Renkl contact

475-254-9169

erika.renkl@yale.edu

Kathy Gerich contact

katherine_gerich@URMC.rochester.edu

19 sites in 2 countries

United States18 sites, 18 recruiting

  • Emory University School of Medicine

    Atlanta, Georgia, 30329

    Amanda Lansdell, 404-712-5586, agoodw7@emory.edu

    Gareth Butler, 404-778-7476, gareth.butler@emory.edu

    Not yet recruiting

  • University of Colorado Anschutz

    Aurora, Colorado, 80045

    Dillan Patel, 720-515-8194, dillan.patel@cuanschutz.edu

    Erika Shelton, 303-724-5865, erika.shelton@cuanschutz.edu

    Recruiting

  • Johns Hopkins University

    Baltimore, Maryland, 21287

    Kori Ribb, 667-306-6955, klough2@jhmi.edu

    Nicki Marcantoni, 410-955-8909, nbair2@jhmi.edu

    Not yet recruiting

  • Parkinson's Disease & Movement Disorders Center of Boca Raton

    Boca Raton, Florida, 33486

    Yatzka Hernandez, 561-392-1818 ext. 2, yhernandez@parkinsonscenter.org

    Fannie Levinson, 561-392-1818 ext. 2, flevinson@parkinsonscenter.org

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Abbey Otterbein, 617-724-7290, aotterbein@mgh.harvard.edu

    Nathan Fogarty, 617-726-2341, nfogarty@mgh.harvard.edu

    Recruiting

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

    Alexandra Gottlieb, 617-667-2501, agottli2@bidmc.harvard.edu

    Aine Russell, 617-667-2351, arussel2@bidmc.harvard.edu

    Not yet recruiting

  • Medical University of South Carolina

    Charleston, South Carolina, 29403

    Sandra Wilson, 843-792-4616, wilsosan@musc.edu

    Lisa Heidelberg, 843-876-0829, heidelbe@musc.edu

    Not yet recruiting

  • University of Texas Houston Medical Center

    Houston, Texas, 77030

    Robert Ritter III, 713-500-7051, robert.ritter@uth.tmc.edu

    Juan Martinez-Lemus, 713-500-7051, juan.d.martinezlemus@uth.tmc.edu

    Not yet recruiting

  • Cleveland Clinic Lou Ruvo Center for Brain Health - Las Vegas

    Las Vegas, Nevada, 89106

    Ruth De Alba, 702-483-6000, dealbar@ccf.org

    Liliana Dumitrescu, 702-483-6016, dumitrl@ccf.org

    Not yet recruiting

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

    Jalina Graham, 603-650-5356, jalina.a.graham@hitchcock.org

    Julie Bursey, 603-653-9948, julie.a.bursey@hitchcock.org

    Not yet recruiting

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

    Michele L Gregorio, PhD, 323-690-9902, michele.gregorio@cshs.org

    Anne Tran, 310-423-1697, anne.tran@cshs.org

    Not yet recruiting

  • University of Minnesota

    Minneapolis, Minnesota, 55414

    Catherine Koukol, 612-624-8974, catk@umn.edu

    Joy Schmidt, 763-913-8367, schmidtj@umn.edu

    Not yet recruiting

  • Weill Medical College of Cornell University

    New York, New York, 10021

    Charles Snajrd-Trinch, 212-746-1685, chs4056@med.cornell.edu

    Gabriella McNamara Lewis, 212-746-1685, gml4002@med.cornell.edu

    Not yet recruiting

  • Yale Medicine

    North Haven, Connecticut, 06473

    MaryClare Kelly, (203) 903-2698, MaryClare.Kelly@yale.edu

    Deanna Sgambato, PA-C, 203-804-4602, deanna.sgambato@yale.edu

    Recruiting

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19107

    Victoria Vaughn, 215-829-3056, victoria.vaughn@pennmedicine.edu

    Nabila Dahodwala, MD, MS

    Recruiting

  • Oregon Health & Science University

    Portland, Oregon, 97239

    Magda Armendariz Sullivan, 503-494-8881, PDResearch@ohsu.edu

    Morgan Wilhelmi, 503-367-4269, wilhelmo@ohsu.edu

    Recruiting

  • University of Texas Health Science Center- San Antonio

    San Antonio, Texas, 78229

    Floyd Jones, 210-450-3158, jonesfa@uthscsa.edu

    Ashley Laroche, 210-450-7249, larochea@uthscsa.edu

    Recruiting

  • Washington University

    St Louis, Missouri, 63110

    Melissa Ammel, 314-747-3470, ammelm@neuro.wustl.edu

    Amy Stiebel, 314-362-5243, a.stiebel@wustl.edu

    Recruiting

Other trials in United States

Canada1 site, 1 recruiting

  • Montreal Neurological Institute-Hospital at McGill University

    Montreal, Quebec, H3A 2B4

    Yara Nasr, 514-396-2947, yara.nasr@mcgill.ca

    Gabriele Riva, 514-398-6083, gabriele.riva@mcgill.ca

    Not yet recruiting

Other trials in Canada

About this study

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 in persons with idiopathic REM Sleep Behavior Disorder (RBD). The Primary Endpoint will be change from baseline in expression of the Parkinson Disease Related Pattern (PDRP) will be assessed using change in 18-flurodeoxyglucose (FDG) Positron Emission Tomography (PET) imaging.

Read the detailed description

Primary Objective: To assess the ability of adalimumab as compared to placebo to reduce or prevent progression of synuclein-related neurodegeneration in persons with idiopathic REM Sleep Behavior Disorder (RBD).

Secondary Objective, Safety: Safety will be assessed by monitoring the incidence of adverse events, clinical laboratory abnormalities, serious infections, signs and symptoms suggestive of new onset demyelinating disease, incidence of new demyelinating lesions on brain MRI scan and number of study participants who develop serum anti-adalimumab antibodies (ADAs).

Secondary Objective, Clinical: To assess the effect of adalimumab treatment on change in clinical measures presumptively related to underlying neurodegeneration. The key secondary endpoint of interest will be a composite outcome. A study participant will be considered to have met the study endpoint upon the attainment of at least 1 of the following milestones at 2 consecutive study visits at least 3 months apart:

  • Increase from baseline of > 2 points on the combined MDS-UPDRS Parts 1b and 2, OR
  • Increase from baseline in MDS-UPDRS Part III motor score > 4 points, OR
  • Decrease from baseline in MoCA of > 3 points, OR
  • Participant is diagnosed with PD, DLB, or MSA by a Movement Disorder specialist or a neurologist specializing in cognitive disorders, OR
  • Participant has initiated pharmacologic treatment for PD-, DLB-, or MSA-related symptoms

Additional (or Exploratory) Objectives:

  • To evaluate the pharmacodynamic effect of adalimumab on biomarkers of immune system dysfunction in RBD patients to predict response to treatment
  • To evaluate the effect of adalimumab on selected biomarkers reflective of neurodegeneration
  • To evaluate effects of adalimumab treatment on selected measures of quality of life

After a 12-week screening period, subjects will be randomized 1:1 to receive active or placebo treatment. Thereafter, subjects will be seen in clinic at 4, 12 and 24 weeks after their initial dose, and then at approximately 24-week intervals up to Week 96. A safety follow-up visit will occur 70 days after the last dose of study treatment. At specified visits, safety and clinical and biomarker assessments will be obtained, and study medication will be dispensed. Quantitative motor and cognitive assessments will be completed at home at intervals between in-person study visits.

At 6-month intervals, subjects will be given a body-worn sensor that they will wear for 7 days to record patterns of activity during sleep and wakefulness.

Subjects who meet one of the clinical secondary endpoints will remain in the study until its termination.

Approximately 25 subjects in each treatment group will be enrolled in an Cerebrospinal Fluid (CSF) biomarker sub-study. Subjects in this sub-study: Individuals participating in the CSF sub-study will undergo lumbar punctures at baseline and at yearly intervals, thereafter, to assess the effects of adalimumab on biomarkers of immune processes and neurodegeneration in the CSF.

Being tested
Adalimumab, Placebo
Keywords
Parkinson Disease Related Pattern, adalimumab, Synucleinopathy
Medical subject headings
REM Sleep Behavior Disorder, Synucleinopathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AdalimumabDrug

    40 mg self-administered subcutaneously using a pre-filled syringe (PFS) every 2 weeks for up to 2 years

  • PlaceboDrug

    40 mg matching placebo self-administered subcutaneously using a pre-filled syringe (PFS) every 2 weeks for up to 2 years

Study groups in NCT06996652
Study groupRoleWhat they receive
AdalimumabExperimentalParticipants in this arm will receive Adalimumab every 2 weeks for up to 2 years
Receives: Drug: Adalimumab
PlaceboPlacebo comparatorParticipants in this arm will receive matching placebo every 2 weeks for up to 2 years
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Parkinson Disease Related Pattern (PDRP) expression

    Change from Baseline to Week 96in the expression of the Parkinson Disease Related Pattern (PDRP) assessed by 18-flurodeoxyglucose (FDG) Positron Emission Tomography (PET).

    Measured: Baseline and Week 96

Secondary outcomes (6)

  1. Percentage of participants that experience adverse events

    Percentage of participants that experience any adverse event

    Measured: up to Week 96

  2. Percentage of participants with clinical laboratory abnormalities

    Percentage of participants with any clinical laboratory abnormalities

    Measured: up to Week 96

  3. Percentage of participants with possible new onset of disease

    Percentage of participants with serious infections and/or signs and symptoms suggestive of new onset demyelinating disease

    Measured: up to Week 96

  4. Percentage of participants with new onset of disease

    Percentage of participants with new demyelinating lesions on brain MRI scan

    Measured: up to Week 96

  5. Percentage of participants with serum anti-adalimumab antibodies (ADAs)

    Percentage of participants who develop serum anti-adalimumab antibodies (ADAs)

    Measured: up to Week 96

  6. Number of participants that meet study endpoint

    This is a composite clinical outcome. A study participant will be considered to have met the study endpoint upon the attainment of at least 1 of the following milestones at 2 consecutive study visits at least 3 months apart:

    • Increase from baseline of > 2 points on the combined MDS-UPDRS Parts 1b and 2, OR
    • Increase from baseline in MDS-UPDRS Part III motor score > 4 points, OR
    • Decrease from baseline in MoCA of > 3 points, OR
    • Participant is diagnosed with PD, DLB, or MSA by a Movement Disorder specialist or neurologist specializing in cognitive disorders, OR
    • Participant has initiated pharmacologic treatment for PD-, DLB-, or MSA-related symptoms

    Measured: up to Week 96

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2025
  2. Study start17 Aug 2026
  3. Primary completion1 Aug 2029 (estimated)
  4. Study completion1 Jan 2030 (estimated)

Resources

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 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants with REM sleep behavior disorder (RBD) who are at risk for developing motor and/or cognitive symptoms of Parkinson's disease or Lewy Body Dementia at up to 15 sites in the United States and Canada
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
108 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06996652
Sponsor's protocol ID
2000038476
Other IDs
2000038206, YPD-001, 1R01AG095016-01
Acronym
PRISMS
Status last verified
Aug 2026
First submitted
21 May 2025
Last updated
8 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All deidentified data not considered PHI and permitted to be released per participants' consent will be made available.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Adalimumab in people with REM Sleep Behavior Disorder, run by Yale University at 19 sites in 2 countries.

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 15 inclusion and 40 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 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Canada. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Erika Renkl (475-254-9169, erika.renkl@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Parkinson Disease Related Pattern (PDRP) expression (time frame: Baseline and Week 96). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06996652.

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 8 Oct 2026.

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