Tuesday, April 9, 2024

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

 

With your risk of Parkinsons post stroke, your competent? doctor and hospital should be ensuring that they know which intervention is better for Parkinsons. Or don't you have a competent doctor or hospital?

 This one or the newest one?Trial of Lixisenatide in Early Parkinson’s Disease April 2024

 

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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

Open AccessPublished:March 27, 2024DOI:https://doi.org/10.1016/j.eclinm.2024.102563

Summary

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

Research in context

Evidence before this study

A comprehensive search was conducted on PubMed from database inception till September 1st, 2023, using the search terms “Parkinson” and “gut microbiota” or “gut microbiome”, without any language or date restrictions. The existing literature supports an early involvement of the gastrointestinal system in the aetiology and progression of Parkinson's disease (PD) for a sub-group of patients, supporting the gut-first versus brain-first hypothesis. During the prodromal phase of the disease, evidence suggests the presence of alpha-synuclein in the enteric nervous system, subclinical gut inflammation, compromised intestinal barrier integrity, and gastrointestinal symptoms like constipation. Several recent meta-analyses comparing the gut microbiota of patients with PD to healthy controls have shown differential abundances of taxa associated with reduced mucosal barrier and increased intestinal inflammation. An additional search was performed on PubMed using the terms “Parkinson” and “microbiota transplantation” which yielded 82 reports predominantly focusing on faecal microbiota transplantation (FMT) as a potential treatment for PD. Four open-label studies with small number of patients have demonstrated beneficial effects on symptoms, mainly constipation. Although technically not a FMT study, a recently conducted pilot study with a randomized and placebo-controlled design (n = 11), using an orally lyophilised donor stool product or matching placebo, was well tolerated and reported reduced constipation, however objective UPDRS motor improvements were transient and not statistically different from placebo. In these studies, adverse events associated with FMT were mild and restricted to transient gastro-intestinal discomfort and diarrhoea.

Added value of this study

We present the results of a one-year, randomized, double-blind, placebo-controlled study of nasojejunal FMT in patients with early-stage PD. This study is the first of its kind with larger sample sizes compared to previously reported trials. The healthy donor FMT group demonstrated significantly greater improvements in motor symptom severity compared to the control group, with the effect becoming more pronounced starting from the 6 to 12 months interval. Objective measurements of gastrointestinal transit indicated improvements in the healthy donor group, starting from the 3 to 6 months interval. No severe adverse events were reported in either group, further supporting the safety profile of FMT.
 
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