Landmark 315 · Trial in people
N-acetylcysteine (Monti)
Will tell us whether a brain-scan change seen in small trials without placebo holds up. Even a good result would not show slowing.
In short
A Philadelphia group reports that intravenous plus oral NAC raised dopamine-transporter scan signal by 3% to 8% and improved symptoms in two small trials with no placebo, and a 50-person follow-up using a different PET scan finishes around January 2027.
- What it is
- Trial in people
- Outcome
- Result due Jan 2027
- When
- 2014–2027
- Size
- 50 people · Phase 2
- Approach
- Help cells clean up
- Research lane
- Oxidative stress
- Trial registry
- NCT02445651
- Last checked
- 22 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
Daniel Monti, Andrew Newberg, George Zabrecky and colleagues at Thomas Jefferson University, Philadelphia.
What happened
NAC (N-acetylcysteine) is a cheap supplement and drug (used to treat paracetamol overdose) that supplies cysteine, the raw material for glutathione. Glutathione is low in the Parkinson's nigra (landmark 129).
- First pilot (2016, PLoS One; NCT02445651). Registered as 51 participants, started March 2014, completed 2022. Patients stayed on standard care and received NAC or sat on a waitlist for 3 months. DaTscan (a scan of dopamine-transporter binding) rose 4.4% to 7.8% in caudate and putamen in the NAC group, with no measurable change in controls; the UPDRS improved by 12.9% (p = 0.01). A lab experiment showed NAC saved more dopamine neurons exposed to rotenone.
- Randomised study (2019, Clin Pharmacol Ther). 42 patients were randomised to weekly IV NAC (50 mg/kg) plus 500 mg orally twice daily for 3 months, or standard care only. DaTscan binding rose by 3.4% to 8.3% against controls (P < 0.05), with symptoms better (P < 0.0001).
- MRI follow-up (2026, Parkinsonism Relat Disord). 44 patients, 6 months; brain-network connectivity changed in the NAC group.
- FdopaPD2 (NCT04459052). Phase 2, open-label crossover, planned 50, comparing against a waitlist, using FDOPA PET (which images dopamine synthesis). Started April 2020; registry shows active, not recruiting, with primary completion (11 April 2025) already reached, no results posted and the record last updated July 2025; study completion estimated January 2027.
Why it moved us toward a cure
These are the best-known human data for raising brain antioxidants in Parkinson's. But participants knew their treatment, and a change in scan signal is not proof of slowing, so the idea has not yet been tested properly.
Outcome
Pending. The Jefferson studies had no placebo. FdopaPD2 reached its primary completion in April 2025 and still has no results; study completion is estimated January 2027, our expected date. A small placebo-controlled Phase 2 from Kurdistan University of Medical Sciences (Sanandaj, Iran; 42 people, 1,200 mg a day for one year, started April 2018, completed December 2021) was registered in July 2025 as NCT07093944; it has no results posted and we have not found a paper, so it cannot be weighed yet.
Sources
- Monti et al., PLoS One 2016, DOI 10.1371/journal.pone.0157602
- Monti et al., Clin Pharmacol Ther 2019, DOI 10.1002/cpt.1548
- Monti et al., Parkinsonism Relat Disord 2026, DOI 10.1016/j.parkreldis.2026.108216
- ClinicalTrials.gov NCT02445651 · NCT04459052 · NCT07093944 (API, 22 Oct 2026)
- Not yet verified: whether the 2019 study is the same trial as NCT02445651; the 2016 pilot's group sizes; whether the 2016 arms were randomised; any result of the Kurdistan placebo-controlled trial NCT07093944 (none posted or found).
How it connects
Built on
- builds on Glutathione loss in the nigra · 1994
Led to
None recorded.