medwireNews: Results of the ReSScue double-blind randomized controlled phase 2 trial show no gastrointestinal benefit for fecal microbiota transplantation in patients with systemic sclerosis.
As reported in The Lancet Rheumatology, there was no significant change in the worst lower gastrointestinal tract (GI) symptoms of bloating and diarrhea experienced over a 12-week study period among those who were and were not given a standardized fecal microbiota transplant.
“Despite the negative outcome, this study offers valuable novel insights for future gastrointestinal tract trials in patients with systemic sclerosis,” write Anna-Maria Hoffmann-Vold (Oslo University Hospital, Norway) and collaborators.
They suggest: “It is possible that the lack of clinical benefit, at least partly, is related to the route or mode of application, chosen dose, interval between the active interventions, or a combination of these factors.”
The study involved 67 individuals (93% women) aged a mean of 58.9 years with confirmed systemic sclerosis. For inclusion, they had to have moderate-to-severe lower GI symptoms as defined by the UCLA-Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 scoring system, with baseline scores for bloating and diarrhea of 1.01 points or higher out of a possible 3.00 points or 0.50 points or higher out of a possible 2.00 points, respectively.
Before the start of the study, all the participants were stratified at a screening visit into two groups according to whether their worst lower GI symptom was bloating or diarrhea. They then underwent a 4–12-week screening phase before being randomly assigned to receive either a standardized anerobic cultivated human intestinal microbiome (ACHIM) or placebo preparation.
Treatment was administered at an endoscopy facility at week 0 and again 2 weeks later, with the preparations instilled directly into the distal duodenum via a gastroduodenoscope over a period of 30–60 seconds. This was followed by a 30-mL infusion of a sterile isotonic solution.
Fecal samples were collected by participants at home at weeks 0, 2, and 12, within the last 48 hours before their study visit.
The primary endpoint selected was the change from baseline to week 12 in the worst bloating or diarrhea, but this showed no difference between the ACHIM- and placebo-treated groups, with mean changes of –0.13 and –0.33, respectively.
Adverse events (AEs) were “mostly mild and short-lived,” report the researchers, who say that, overall, the fecal transplants were “well tolerated.”
In all, 48% of the 33 people who received fecal transplants and 56% of the 34 who received placebo experienced any AEs, the most common of which were abdominal pain (15 vs 6%) and nausea (9 vs 12%). Four serious AEs were recorded – three (9%) in the ACHIM group (myocardial infarction, transverse myelitis, and intestinal submucosa perforation), and one (3%) in the placebo group (acute abdominal pain requiring hospitalization).
In an accompanying comment, Shu Wen Tay and Andrea Hsiu Ling Low, both from Singapore General Hospital, praise the researchers “for undertaking this challenging study.”
The microbial composition of the fecal samples was tested during the study using quantitative polymerase chain reaction but showed no significant changes in the diversity of bacterial species either within or between samples, which the commentators say is a “surprising finding.”
However, as “there was increased abundance of bacterial species present in the ACHIM group,” they suggest that there was “engraftment of ACHIM-derived bacteria, but this was insufficient to induce gut microbiota composition change,” they point out.
Tay and Low propose a number of reasons why the trial’s findings were negative, such as the type of microbiota used for the transplant, and the “permissive use” of antibiotics in “around 30% in both groups.”
They write: “[F]or now, we conclude that faecal microbiota transplantation is not quite ready for prime time but holds promise for the future with refinement of trial design.”
The commentators conclude that future studies might look at using different types of fecal preparation, such as those from “so-called super-donors,” or alternative instillation modalities, and enriching the study population with patients who have the same predominant GI symptoms, or those with an earlier stage of systemic sclerosis.
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Lancet Rheumatol 2025; doi:10.1016/S2665-9913(24)00334-5
Lancet Rheumatol 2025; doi:10.1016/S2665-9913(24)00376-X
