Protocol of the LEONORA randomized clinical trial: Lower gastrointestinal symptom burden by prophylaxis with synbiotics after colorectal cancer surgery

A key component of colorectal cancer (CRC) treatment is the surgical resection of the tumor, accompanied by antibiotic treatment and often chemotherapy, which severely alter the gut function and its microbiome. Thus, CRC patients commonly suffer from gastrointestinal symptoms like chronic diarrhea, which can persist in some patients for several years. Synbiotics are a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confer a health benefit on the host. Previous randomized controlled trials have shown that synbiotics reduce rates of post-operative infections and related complications, diarrhea incidence, and inflammation. However, data on the gastrointestinal quality of life are very sparse. The proposed LEONORA trial is a randomized controlled trial with 206 CRC patients, who shall be recruited in 10 German clinics. While 103 patients in arm 1 will receive a placebo, 103 patients in arm 2 will be given a daily synbiotic treatment for 12 weeks with 50 billion colony-forming units of 12 live bacterial strains. After the wound healing phase, patients in the intervention arm will additionally receive the dietary fiber inulin from weeks 5 to 12. Every 2 weeks, the inulin dosage will be stepwise increased from 3 g to 10 g per day to slowly train the gut microbiome and avoid flatulence. The study participants in the placebo group, on the other hand, receive maltodextrin as a second placebo, which is very similar to inulin in appearance and taste, but does not affect the gut microbiome. The primary endpoint is the gastrointestinal quality of life 90 days after surgery. Further outcomes include rates of infections, cancer recurrence, cancer survival, blood-based inflammatory biomarkers, and metabolites. Stool samples will be collected to additionally address changes in the gut microbiome and metabolome composition. The 3-month therapy with synbiotics could be a well-tolerated and very cost-effective approach to increase the gastrointestinal quality of life of CRC patients. Thus, the results of the proposed LEONORA trial will be of high relevance for both caregivers and CRC patients. German Clinical Trials Register (DRKS): DRKS00034919, November 21, 2024; https://www.drks.de/search/de/trial/DRKS00034919.