Landmark 181 · Trial in people
Intranasal glutathione, Phase IIb
Everyone improved, including people on placebo, so it showed no benefit over placebo in 45 people. One person on the high dose had a heart problem.
In short
A nose-spray form of the brain's own antioxidant, glutathione, improved scores in all groups, including placebo, so the study could not show it works.
- What it is
- Trial in people
- Outcome
- Mixed or early results
- When
- 2015–2017
- Size
- 45 people · Phase 2
- Approach
- Help cells clean up
- Research lane
- Oxidative stress
- Trial registry
- NCT02424708
- Last checked
- 19 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
Laurie Mischley and colleagues; the registered sponsor is Bastyr University, Seattle (NCT02424708). Published in the Journal of Parkinson's Disease 2017 (pages 289–299). This is the second study; the first, a randomised Phase I/IIa, was in Movement Disorders in 2015 (DOI 10.1002/mds.26351). The registry shows the trial ran April 2015 to April 2016.
What happened
The Parkinson's nigra holds roughly 40% less glutathione (landmark 129). Glutathione taken by mouth or drip barely reaches the brain, so a nasal route was tried.
- Design. Phase IIb, double-blind, placebo-controlled. 45 people (Hoehn and Yahr 1–3). Saline, 100 mg or 200 mg glutathione three times a day for 3 months, then a 1-month washout.
- Result. Every group improved, including placebo. The high dose improved total UPDRS by 4.6 points (p=0.0025) and motor UPDRS by 2.2 (p=0.0485) from baseline. Neither dose was superior to placebo. The authors call the placebo response more robust than in previous Parkinson's studies.
- Safety. One high-dose participant developed cardiomyopathy.
- Authors' view. The symptomatic effects justify a delayed-start or washout design for disease-modification trials; longer, larger studies are needed.
Why it moved us toward a cure
It tested the oxidative-stress finding of landmark 129 directly, and showed how large a placebo response can be in short trials. It was a 3-month symptom study, not a test of slowing.
Outcome
Open: inconclusive. A different study, NCT05266417 (intranasal insulin plus glutathione versus placebo, Phase 2, Gateway Institute for Brain Research), is registered as recruiting, with 56 planned and completion estimated November 2027. I found no Phase 3 of glutathione alone.
Sources
- Mischley et al., J Parkinsons Dis 2017, DOI 10.3233/JPD-161040 (PMID 28436395)
- ClinicalTrials.gov NCT02424708 · NCT05266417 (API, 19 Oct 2026)
- Not yet verified: the 40% figure (it comes from landmark 129); the arm sizes.
How it connects
Built on
- tests Glutathione loss in the nigra · 1994
Led to
- builds on NOSE-PD: nasal insulin plus glutathione · 2022