Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial

Arnout Bruggeman; Charysse Vandendriessche; Hannelore Hamerlinck; Danny De Looze; David J Tate; Marnik Vuylsteke; Lindsey De Commer; Lindsay Devolder; Jeroen Raes; Bruno Verhasselt; Debby Laukens; Roosmarijn E Vandenbroucke; Patrick Santens

doi:10.1016/j.eclinm.2024.102563

Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial

EClinicalMedicine. 2024 Mar 27:71:102563. doi: 10.1016/j.eclinm.2024.102563. eCollection 2024 May.

Authors

Arnout Bruggeman^{1

2

3

4}, Charysse Vandendriessche^{3

4}, Hannelore Hamerlinck^{2

5}, Danny De Looze^{2

6}, David J Tate^{2

6}, Marnik Vuylsteke^{3

7}, Lindsey De Commer^{8

9}, Lindsay Devolder^{8

9}, Jeroen Raes^{8

9}, Bruno Verhasselt^{2

5}, Debby Laukens², Roosmarijn E Vandenbroucke^{3

4}, Patrick Santens^{1

2}

Affiliations

¹ Department of Neurology, University Hospital Ghent, Ghent, Belgium.
² Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
³ VIB-UGent Center for Inflammation Research, VIB, Ghent, Belgium.
⁴ Faculty of Sciences, Ghent University, Ghent, Belgium.
⁵ Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.
⁶ Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium.
⁷ Statistics for Biosciences, Gnomixx, Melle, Belgium.
⁸ Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium.
⁹ VIB-KU Leuven Center for Microbiology, VIB, Leuven, Belgium.

Abstract

Background: Dysregulation of the gut microbiome has been implicated in Parkinson's disease (PD). This study aimed to evaluate the clinical effects and safety of a single faecal microbiota transplantation (FMT) in patients with early-stage PD.

Methods: The GUT-PARFECT trial, a single-centre randomised, double-blind, placebo-controlled trial was conducted at Ghent University Hospital between December 01, 2020 and December 12, 2022. Participants (aged 50-65 years, Hoehn and Yahr stage 2) were randomly assigned to receive nasojejunal FMT with either healthy donor stool or their own stool. Computer-generated randomisation was done in a 1:1 ratio through permutated-block scheduling. Treatment allocation was concealed for participants and investigators. The primary outcome measure at 12 months was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score obtained during off-medication evaluations. Intention-to-treat analysis was performed using a mixed model for repeated measures analysis. This completed trial is registered on ClinicalTrials.gov (NCT03808389).

Findings: Between December 2020 and December 2021, FMT procedures were conducted on 46 patients with PD: 22 in the healthy donor group and 24 in the placebo group. Clinical evaluations were performed at baseline, 3, 6, and 12 months post-FMT. Full data analysis was possible for 21 participants in the healthy donor group and 22 in the placebo group. After 12 months, the MDS-UPDRS motor score significantly improved by a mean of 5.8 points (95% CI -11.4 to -0.2) in the healthy donor group and by 2.7 points (-8.3 to 2.9) in the placebo group (p = 0.0235). Adverse events were limited to temporary abdominal discomfort.

Interpretation: Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages.

Funding: Flemish PD patient organizations (VPL and Parkili), Research Foundation Flanders (FWO), Biocodex Microbiota Foundation.

Keywords: Clinical trial; Faecal microbiota transplantation; Gut microbiota; Gut-brain axis; Parkinson's disease.

Associated data

ClinicalTrials.gov/NCT03808389