Summary
Background
The gut microbiota modulates peripheral immunity, which is altered in amyotrophic lateral sclerosis (ALS). Faecal microbiota transplantation (FMT) may exert immunological effects, but its impact in ALS remains unclear.
Methods
FETR-ALS was a multicentre, randomised, masked, sham-controlled proof-of-concept trial conducted at four Italian ALS centres. Adults with ALS of 18 months duration or less and forced vital capacity of at least 70% predicted were randomly assigned (2:1) to receive FMT or a sham procedure (SP). The intervention consisted of two nasojejunal administrations of screened-donor faecal suspension at baseline and month 6, without antibiotic preconditioning. The primary endpoint was change in circulating Tregs among CD4+ T cells at 6 months. Secondary endpoints included safety, ALS Functional Rating Scale–Revised slope, respiratory and nutritional measures, survival, and exploratory biomarker profiles. Analyses followed the intention-to-treat principle.
ClinicalTrials.gov identifier:
NCT03766321.
Findings
Between 2020 and 2024, 43 individuals were screened and 42 were enrolled and randomly assigned to FMT (n = 28; mean age 56.1 years [SD 8.2]; 14 [50%] male) or SP (n = 14; 59.6 years [9.1]; eight [57%] male). Overall, 29 participants completed the second procedure and 6-month follow-up, and Treg measurements were available for 28. The primary outcome was not met: at 6 months, 8/18 (44%) participant receiving FMT versus 2/10 (20%) receiving SP achieved a ≥20% increase in circulating Tregs (odds ratio [OR] 3.20, 95% CI 0.59–25.36; p = 0.21). Mean Treg increase was 2.36 percentage points higher with FMT (95% CI 0.19–4.55; p = 0.04). ALSFRS-R declined by −1.07 points/month in the SP group and −0.76 points/month in the FMT group, with a between-group difference in monthly decline of 0.31 points/month favouring FMT (95% CI 0.11–0.51; p = 0.002). Conversely, at month 6, the MRC score was lower in the FMT group than in the SP group (0.75 versus 0.89; mean difference −0.13, 95% CI –0.26 to 0.00; p = 0.042). FMT was associated with 32 adverse events (12.5% severe) versus 14 (28.6% severe) in SP, mostly gastrointestinal or infectious.
Interpretation
In this exploratory trial, FMT was not associated with major safety concerns. Although the primary endpoint was not met, FMT was associated with a modest increase in circulating Tregs.
Funding
Italian Ministry of Health.
