Title : Efficacy and safety of Mucuna pruriens seed extract effervescent powder as adjunctive therapy for levodopa-related wearing-off in Parkinson’s disease: A randomized, double-blind, placebo-controlled pilot trial
Abstract:
Background: Wearing-off is a common complication of long-term levodopa therapy in Parkinson’s disease (PD), resulting in recurrent motor symptoms and impaired daily functioning. Mucuna pruriens (MP), a natural source of levodopa, has potential as an adjunctive therapy, although supporting clinical evidence remains limited.
Objective: To evaluate the preliminary efficacy and safety of MP seed extract effervescent powder as adjunctive therapy in patients with PD experiencing wearing-off.
Methods: This 12-week, phase IIa, randomized, double-blind, placebo-controlled, parallel-group pilot trial was conducted at Chao Phya Abhaibhubejhr Hospital, Thailand. Eligible patients were aged 20–80 years, had modified Hoehn and Yahr stages 2–4, and experienced wearing-off despite stable levodopa therapy (≥200 mg/day). Participants received standard treatment plus MP seed extract effervescent powder (n=7) or matching placebo (n=6), with protocol-guided dose adjustments. Outcomes assessed at baseline and weeks 4, 8, and 12 included total daily OFF time, Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II and III, Thai Parkinson’s Disease Questionnaire-8 (PDQ-8), and safety. Efficacy was initially evaluated using the planned per-protocol (PP) analysis of treatment completers. A subsequent post hoc exploratory analysis employed baseline-adjusted longitudinal linear mixed models (LMMs) using available observations from all randomized participants. Safety was assessed in all treated participants.
Results: Thirteen patients were randomized, and eight completed treatment (four per group). In the planned PP analysis, the between-group difference in total daily OFF time at week 12 was −172.85 min/day (95% CI −625.45 to 279.75; p=0.386). In the post hoc LMM analysis, the adjusted between-group difference favored MP (−195.78 min/day; 95% CI −327.47 to −64.09; p=0.004). The exploratory analysis also favored MP for UPDRS Part II (−6.38 points; p=0.001), UPDRS Part III (−12.85 points; p<0.001), and PDQ-8 (−2.18 points; p=0.036). Five participants discontinued treatment (38.5%), including four due to adverse events (three MP, one placebo). Dyskinesia was reported in five MP participants (71.4%) and one placebo participant (16.7%). No serious adverse events were reported.
Conclusion: The planned PP analysis did not demonstrate a statistically significant between-group difference in daily OFF time. Post hoc exploratory analysis suggested potential benefits of adjunctive MP for wearing-off, motor function, daily activities, and quality of life. However, the small sample size, substantial attrition, post hoc analysis, and tolerability concerns preclude definitive conclusions. Larger, adequately powered trials incorporating pharmacokinetic evaluation and careful safety monitoring are warranted.
