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.

IF 9.6 1区医学 Q1 MEDICINE, GENERAL & INTERNAL EClinicalMedicine Pub Date : 2024-03-27 eCollection Date: 2024-05-01 DOI:10.1016/j.eclinm.2024.102563

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

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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.

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轻中度帕金森病患者粪便微生物群移植的安全性和有效性（GUT-PARFECT）：一项双盲、安慰剂对照、随机、2 期试验。

背景：肠道微生物群失调与帕金森病（PD）有关。本研究旨在评估单次粪便微生物群移植（FMT）对早期帕金森病患者的临床效果和安全性：GUT-PARFECT试验是一项单中心随机、双盲、安慰剂对照试验，于2020年12月1日至2022年12月12日在根特大学医院进行。参与者（50-65 岁，Hoehn 和 Yahr 2 期）被随机分配到接受鼻空肠粪便造影术（FMT）的健康捐献者粪便或自己的粪便。计算机生成的随机分配比例为 1:1。参与者和研究人员均不知道治疗分配情况。12个月时的主要结果指标是非用药评估期间运动障碍协会-统一帕金森病评分量表（MDS-UPDRS）运动评分的变化。采用重复测量混合模型进行了意向治疗分析。这项已完成的试验已在 ClinicalTrials.gov (NCT03808389) 上注册：在 2020 年 12 月至 2021 年 12 月期间，对 46 名帕金森病患者进行了 FMT 治疗，其中健康供体组 22 人，安慰剂组 24 人。在基线、FMT 术后 3、6 和 12 个月进行了临床评估。对健康供体组的 21 名参与者和安慰剂组的 22 名参与者进行了全面的数据分析。12 个月后，健康供体组的 MDS-UPDRS 运动评分显著改善，平均改善 5.8 分（95% CI -11.4--0.2），安慰剂组改善 2.7 分（-8.3-2.9）（p = 0.0235）。不良反应仅限于暂时性腹部不适：我们的研究结果表明，单次 FMT 对早期帕金森病患者的运动症状有轻微但持久的改善作用。这些发现凸显了调节肠道微生物组作为一种治疗方法的潜力，值得在不同疾病阶段的更大规模的帕金森病患者群体中进一步探索FMT：佛兰德斯PD患者组织（VPL和Parkili）、佛兰德斯研究基金会（FWO）、Biocodex微生物群基金会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EClinicalMedicine Medicine-Medicine (all)

CiteScore

18.90

自引率

1.30%

发文量

506

审稿时长

22 days

期刊介绍： eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.