Randomized, placebo-controlled trial of N-acetylcysteine in Parkinson's disease patients: a pilot study

This pilot trial evaluated the one-year tolerability of oral N-acetylcysteine (NAC) 1200 mg/day in Parkinson's disease (PD) and explored associations with clinical progression, levodopa dose, and striatal dopamine-transporter imaging. Forty-two patients were randomized to NAC or matching placebo twice daily for 12 months in addition to usual care. Completers (n = 32) were assessed at baseline and 12 months with the original UPDRS parts I-IV, 99mTc-TRODAT-1 SPECT, prescribed levodopa dose, and liver/kidney tests. Analyses included paired t-tests, Welch tests of change scores, and linear mixed-effects models with a group × time interaction adjusted for age, sex, and disease duration. No multiplicity correction was applied; results are exploratory. Thirty-two of 42 randomized patients completed both visits. Total UPDRS increased in both groups, but less with NAC than placebo (mean Δ + 5.4 vs. + 9.5 points; difference - 4.1, 95% CI - 7.6 to - 0.5; p = 0.028; mixed-model group × time p = 0.024). Mood-item change also differed (difference - 0.64, 95% CI - 1.17 to - 0.11; p = 0.020). TRODAT binding declined less with NAC (difference in change + 5.5 units, 95% CI 1.7 to 9.3; p = 0.006; group × time p = 0.004). The ≤ 4-year subgroup comprised 9/17 (53%) NAC and 7/15 (47%) placebo participants and showed a similar pattern. Levodopa-dose change was not significant between groups after ANCOVA adjustment for baseline dose, age, sex, and disease duration (adjusted difference - 86 mg/day, 95% CI - 235 to + 64; p = 0.25). Completer laboratory values were stable; discontinuations were not characterized for adverse events. One-year oral NAC was associated with more favorable exploratory clinical and imaging trajectories than placebo. Completer laboratories were unremarkable, but safety cannot be established from completers alone. These data do not establish disease modification and require confirmation in a larger, prospectively powered trial.