Pingchan Granule for objective and subjective insomnia in Parkinson's Disease: a multicentre, randomized, controlled, double-blind trial

Abstract

Abstract Background Insomnia is a common and disabling nonmotor manifestation of Parkinson’s disease (PD). Drugs improving both parkinsonism and sleep would be of great benefit to patients with PD-related insomnia. Pingchan granule (PCG) is a traditional Chinese medicine for PD. The objective of this study was to test the efficacy and safety of PCG for insomnia associated with PD. Methods In this multicenter, randomized, double-blind, placebo-controlled trial, 100 participants were included and followed for 16 weeks (12-week treatment, 4-week follow-up after intervention), randomly assigned to receive PCG or placebo at a 1:1 ratio. The primary outcome was subjective PD-related insomnia evaluated by Parkinson’s disease sleep scale 2 (PDSS-2) score. Secondary outcomes included objective parameters of nighttime sleep by polysomnography and serum biomarker. As secondary outcomes, we also evaluated Insomnia Severity Index (ISI) score, Epworth Sleepiness Scale (ESS) score, rapid eye movement sleep behaviour disorder screening questionnaire (RBDSQ) score, Movement Disorder Society Unified Parkinson’s Rating Scale (MDS-UPDRS) I, II,and III scores, and Parkinson's disease questionnaire (PDQ-39) score. Assessments were conducted at baseline (T0), week 4 (T1), week 8 (T2), week 12 (T3) and week 16 (T4). Results The PCG group had significantly greater amelioration in PDSS-2 score than placebo group, as well as its domain scores of overall quality of night’s sleep, sleep onset and maintenance insomnia, nocturnal restlessness, nocturnal psychosis, nocturnal motor symptoms, and daytime dozing. PCG was associated with significant improvement in sleep efficiency, N3 sleep time, total sleep time, and interleukin (IL)-2/IL-4 ratio. Improvements of ISI, ESS, RBDSQ, MDS-UPDRS I, II, III, and PDQ-39 scores were also observed in PCG group compared with the placebo group Conclusions This trial provided class I evidence for the efficacy of PCG in treating insomnia in PD according to a wide range of subjective and objective sleep parameters with good tolerance, supporting that PCG might be a viable alternative in the management insomnia in PD. Trial registration: Chinese Clinical Trial Register, ChiCTR-INR-17011949 (11/07/2017).