A randomized double-blind placebo-controlled multicenter trial of Bushen Yisui and Ziyin Jiangzhuo formula for constipation in Parkinson disease

Abstract

Introduction: Constipation is a common nonmotor symptom of Parkinson disease (PD). Constipation can also impact patient's quality of life. Chinese herbal medicines have been used for the treatment of constipation in PD. This trial will evaluate the efficacy and safety of a Chinese herbal formula Bushen Yisui and Ziyin Jiangzhuo (BYZJ) for the treatment of constipation in PD.

Methods and analysis: This randomized, double-blind, placebo-controlled, multicenter clinical trial will involve 4 hospitals in Beijing, China. The study will aim to recruit 90 PD patients with constipation between 30 and 80 years-of age with a score of 1 - 4 on the Hoehn and Yahr scale. Once recruited, Patients will be randomized into a BYZJ group or a placebo group in a 2:1 ratio. The trial will include a 1-week run-in period, a 4-week double-blind treatment period, a 4-week and a 12-week follow-up period. All patients will be educated about PD-related constipation during the run-in period. BYZJ granules and simulated granules will be administered twice daily for 4 weeks to the BYZJ group and the placebo group respectively. Assessments will be performed during run-in period, before the start of treatment (baseline, week 0), and at 4, 8, and 16 weeks. The primary outcome will be measured with the Constipation Severity Instrument, and secondary outcomes will be evaluated with the Patient Assessment of Constipation Quality of Life questionnaire, Bristol Stool Form Scale, Movement Disorders-Unified Parkinson Disease Rating Scale, Nonmotor Symptoms Scale, PD Sleep Scale, Parkinson Fatigue Scale-16. Laxative use (dose and frequency) will also be recorded. Intention-to-treat and per-protocol set analyses will be used to compare symptom improvement between the 2 groups. Any adverse events will be recorded.

Discussion: If found effective and safe, BYZJ formula will be one of Chinese herb to treat constipation and even other nonmotor or motor symptoms in PD patients. The results will sustain the broader use of BYZJ formula in PD.

Figure 1

Study design flow chart. The 17-wk study will include a 1-wk run-in period, an intervention time of 4 wk, 4-wk, and 12-wk washout follow-up. Efficacy will be assessed at baseline (week 0) and at 4, 8,16 wk and safety will be assessed at baseline (week 0) and at 4, 16 wk.

Figure 2

Time schedule of enrollment, interventions, and assessments: In the run-in period, Subjects will receive health education on constipation by specialist personnel and inform consent, General patient information will be collected; At baseline (week 0) and at 4, 8, 16 wk, CSI will be used to assess the severity of constipation; the PAC-QOL questionnaire to evaluate the impact of constipation on the quality of life of patients with PD; and BSFS to assess stool characteristics. The MDS-UPDRS scale will be used to comprehensively evaluate patients’ daily life experience including MS, NMS, and motor complications. The NMSS allows quantitative evaluation of NMS of PD; the PDSS is used to assess sleep quality in PD patients; and PFS-16 measures the severity of fatigue; the Physiologic information and Safety indices will also be tested at baseline (week 0) and at 4, 16 wk; adverse events will be recorded during the research. BSFS = bristol stool form scale, CSI = constipation severity instrument, MDS-UPDRS = the new world movement disorders comprehensive Parkinson disease rating scale, NMS = nonmotor symptoms, NMSS = nonmotor symptoms scale, PAC-QOL = patient assessment of constipation quality of life questionnaire, PDSS = Parkinson disease sleep scale, PFS-16 = Parkinson fatigue scale.