Landmark 225 · Trial in people
PRISMS: adalimumab in RBD
Tests whether calming inflammation can hold off Parkinson's in people with a sleep disorder that often comes first. It measures a brain-scan pattern, so it cannot prove that Parkinson's was prevented.
In short
The first registered placebo-controlled drug trial I could find that aims to stop people with REM sleep behaviour disorder from developing Parkinson's or Lewy body dementia; the Path to Prevention platform trial is being set up alongside.
- What it is
- Trial in people
- Outcome
- Result due Aug 2029
- When
- 2026–2029
- Size
- 108 people · Phase 2
- Research lane
- Trial methods & regulation
- Trial registry
- NCT06996652
- Last checked
- 18 Oct 2026
The research record
This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".
Who
Yale University (principal investigator Jesse Cedarbaum), with the Parkinson Study Group, the University of Rochester coordination centre, the National Institute on Aging and the Marcus Foundation. Registered as NCT06996652 (trial name PRISMS).
What is being tested
Adalimumab, an antibody that blocks the inflammation signal TNF, versus placebo. Dose 40 mg by self-injection every 2 weeks for up to 2 years.
- Design. Phase 2, randomised, quadruple-masked, purpose "prevention". 108 people with REM sleep behaviour disorder (landmark 221) at up to 15 sites in the US and Canada.
- Status. Recruiting; start 17 August 2026; primary completion estimated 1 August 2029; study completion 1 January 2030 (registry verified 2026-08, last updated 8 October 2026).
- Path to Prevention (P2P). Separately, the Michael J. Fox Foundation and the PPMI team (landmark 24) are building P2P, a platform trial in which several drugs would be tested under one master protocol in people with early-stage synuclein disease (seed-amplification positive, dopamine deficit). Its protocol synopsis was updated 31 March 2026 and the Foundation is seeking drug partners. No P2P drug, size or readout date was found, and I found no ClinicalTrials.gov record under that name.
What would count as success
Primary measure: change from baseline to week 96 in the Parkinson's disease-related pattern (PDRP), a brain-metabolism signature read from FDG-PET scans. Lower rise in PDRP on adalimumab than on placebo would suggest it slows synuclein-related neurodegeneration. The trial is not powered to show delay of clinical conversion.
Sources
- ClinicalTrials.gov NCT06996652 (record read via API)
- PPMI, Path to Prevention platform trial page
- Not yet verified: the scientific rationale for adalimumab (no paper read); any other RBD drug trials with a prevention aim (idebenone NCT04534023, n=28, Phase 2, is registered for iRBD but was not read); P2P's first drug, size and start date.
How it connects
Built on
- builds on REM sleep behaviour disorder becomes Parkinson's · 1996
- uses PPMI launches · 2010
Led to
None recorded.