Safety and feasibility of faecal microbiota transplantation for patients with Parkinson's disease: a protocol for a self-controlled interventional donor-FMT pilot study

Abstract

Introduction: Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson's disease (PD) via the gut-brain axis. The gut microbiota can also influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by faecal microbiota transplantation (FMT) could be a supportive treatment strategy.

Methods and analysis: We have developed a study protocol for a single-centre, prospective, self-controlled, interventional, safety and feasibility donor-FMT pilot study with randomisation and double-blinded allocation of donor faeces. The primary objectives are feasibility and safety of FMT in patients with PD. Secondary objectives include exploring whether FMT leads to alterations in motor complications (fluctuations and dyskinesias) and PD motor and non-motor symptoms (including constipation), determining alterations in gut microbiota composition, assessing donor-recipient microbiota similarities and their association with PD symptoms and motor complications, evaluating the ease of the study protocol and examining FMT-related adverse events in patients with PD. The study population will consist of 16 patients with idiopathic PD that use levodopa and experience motor complications. They will receive FMT with faeces from one of two selected healthy human donors. FMT will be administered via a gastroscope into the duodenum, after treatment with oral vancomycin, bowel lavage and domperidone. There will be seven follow-up moments during 12 months.

Ethics and dissemination: This study was approved by the Medical Ethical Committee Leiden Den Haag Delft (ref. P20.087). Study results will be disseminated through publication in peer-reviewed journals and international conferences.

Trial registration number: International Clinical Trial Registry Platform: NL9438.

Keywords: Faecal Microbiota Transplantation; Microbiota; Parkinson's disease; Protocol; safety.

Figure 1

Graphical abstract of study design and study procedures. V1: screening visit: unspecified time point, V2: baseline, V3: 1 week after baseline (standard-of-care), V4: FMT and 1 week after standard of care, V5: 1 week post-FMT, Tel 1: 2 weeks post-FMT, Tel 2: 6 weeks post-FMT, V6: 3 months post-FMT, V7: 12 months post-FMT. The baseline questionnaire includes questions on health status, disease-related variables and medication use (PD and non-PD). Part of the questionnaires are filled in by the participant prior to a visit/telephone appointment and these include questions on health status, diet, medication use, constipation (Cleveland clinical constipation score and Rome IV constipation criteria), SENS-PD, Q10 (wearing off) and MDS-UPDRS IB and II (and a study load questionnaire at V6). MDS-UPDRS IA, III and IV (III not during telephone appointments) questionnaires and examinations are applied by the investigator at baseline or during standard-of care and FMT follow-up visits. FMT, faecal microbiota transplantation; FU, follow-up, H&Y, Hoehn and Yahr scale; IC, informed consent; m, month(s); MDS-UPDRS, Movement Disorder Society Unified Parkinson’s Disease Rating Scale; MoCA, Montreal Cognitive Assessment; (S)AE, (serious) adverse event; SENS-PD, Severity of Non-dopaminergic Symptoms in Parkinson’s Disease; Tel, telephone appointment; V, visit; w, week(s).