A pilot study of the feasibility and safety of faecal microbiota transplantation in adults with alcohol use disorder and alcohol-related liver disease

Participants randomised to the intervention arm will receive faecal microbiota transplantation (FMT), administered as a single rectal enema at Week 0. Intervention name and product Faecal microbiota transplantation using BIOMICTRA (BiomeBank), an FMT product included in the Australian Register of Therapeutic Goods (ARTG 399066). The product is supplied as two 50 mL frozen syringes, providing a total administered volume of 100 mL containing 25 g of donor stool. BIOMICTRA is included in the ARTG for restoration of the gut microbiota in the treatment of recurrent Clostridioides difficile infection. Its use in this trial for alcohol use disorder and alcohol-associated liver disease is outside the approved indication and will occur under the Clinical Trial Notification scheme. Dose and treatment duration Each participant allocated to the intervention arm will receive one FMT treatment comprising two 50 mL syringes administered sequentially as a single 100 mL rectal enema containing 25 g of donor stool. Minimum dose to be tested: one administration of 100 mL containing 25 g of donor stool. Maximum dose to be tested: one administration of 100 mL containing 25 g of donor stool. The intervention will be administered once only. No repeat dosing will occur during the 12-week primary follow-up or the extended follow-up to Month 6. Timing and setting The FMT enema will be administered at Week 0, on day 5 ± 2 of the participant’s supervised inpatient alcohol-withdrawal admission at the De Paul House residential Alcohol and Other Drug Withdrawal Unit, St Vincent’s Hospital Melbourne. The inpatient admission is expected to last 7 ± 2 days. Mode of delivery and administration procedure FMT will be administered face-to-face to an individual participant by the rectal route. The participant will be positioned in the left lateral decubitus position. A sterile, soft silicone Foley catheter of 14–16 Fr will be lubricated and inserted approximately 3–5 cm into the rectum without inflation of the distal balloon. The contents of the two 50 mL syringes will be instilled sequentially while the catheter remains in position. Following administration, the catheter will be removed and the participant will be repositioned prone with a pillow beneath the hips. The participant will be asked to retain the instillate for at least 30 minutes, and the actual retention time will be recorded. No bowel preparation, laxative, antibiotic preconditioning, sedation or endoscopy will be used as part of the intervention. Intervention provider and training The intervention will be administered by a study nurse or medically qualified investigator who has completed protocol-specific training and documented competency assessment. Authorisation to administer the intervention will be recorded in the trial delegation log. Relevant study personnel will hold current Good Clinical Practice certification and will be trained in product handling, chain of custody, participant identification, confirmation of eligibility and allocation, rectal-enema administration, recognition and reporting of adverse events, protocol-deviation documentation and completion of study source documents. Competency will be documented before the staff member performs the procedure. Adherence and intervention fidelity As this is a single, directly administered intervention, adherence will be assessed by documenting whether the allocated FMT treatment was administered and whether administration was complete. A participant-specific administration checklist will record: - confirmation of participant identity, eligibility and treatment allocation; - product identity, batch or lot number and expiry date; - volume delivered and completeness of administration; - date and time of administration; - retention time; - immediate tolerability events; - post-procedure observations; and - any procedural or protocol deviations. Intervention fidelity will be supported through the study administration procedure, protocol-specific training, documented competency, the delegation log, the participant-specific administration checklist, source-data verification and trial monitoring. Post-administration monitoring Participants will be observed for at least two hours following FMT administration. Vital signs will be recorded at baseline and approximately 30, 60 and 120 minutes after administration. Immediate adverse events will be documented, and participants will receive written post-procedure safety information and emergency contact details. A safety telephone call will be conducted approximately 48–72 hours after the procedure.

Participants randomised to the intervention arm will receive faecal microbiota transplantation (FMT), administered as a single rectal enema at the Week 0 baseline/randomisation visit. Non-proprietary intervention name: faecal microbiota transplantation product, derived from screened healthy donor stool. The final Australian TGA-compliant stool-bank FMT product and supplier will be confirmed before trial commencement. Brand or supplier names will not be used as the primary intervention name. Dose: Each participant allocated to the intervention arm will receive a single dose of the faecal microbiota transplantation (FMT) product, administered once as a rectal (retention) enema at the Week 0 visit. The planned product is likely (pending approval) is a 150 g suspension per single-donor unit. One unit (nominal 150 g suspension) will be thawed and instilled as a single enema. - Minimum dose to be tested: one FMT unit (nominal 150 g suspension), administered once. - Maximum dose to be tested: one FMT unit (nominal 150 g suspension), administered once Duration of treatment: single administration only at Week 0. There will be no repeat dosing during the 12-week primary follow-up period. Mode of delivery: rectal enema, administered face-to-face to an individual participant at St Vincent’s Hospital Melbourne. Administration: the intervention will be administered by a trained, delegated, unblinded clinician or nurse with relevant experience in rectal therapy administration and protocol-specific training in FMT handling, administration, adverse event recognition, Good Clinical Practice and study documentation. The person administering the intervention will not be involved in outcome assessment. Adherence and fidelity: as this is a single administered intervention, adherence will be assessed by direct documentation of whether the full allocated FMT dose was administered. A per-participant administration checklist will record participant identity, eligibility confirmation, product identity, batch/lot number, expiry date, dose/volume administered, completeness of administration, administration time, post-procedure observation and any protocol deviation. Participants will be observed after administration for immediate adverse events according to the study safety monitoring plan. Protocol-specific training will be completed and documented (training log and delegation log) before any participant is dosed. Training is coordinated by the Coordinating Principal Investigators and the study coordinator; Personnel who prepare and administer the FMT/placebo enema (a designated, unblinded study nurse and/or pharmacist experienced in rectal therapy) will complete approximately 4–5 hours of training, delivered as four in-person modules of about one hour each plus a competency assessment: • Module 1 — FMT product handling: cold-chain receipt, frozen storage, controlled thaw, chain-of-custody, and batch/expiry verification per the Lifeblood product insert and study SOP. • Module 2 — Enema administration: participant positioning, instillation technique, retention, and post-procedure observation. • Module 3 — Safety: recognition, grading and reporting of AEs, SAEs and adverse events of special interest (including infection/sepsis surveillance), escalation pathways, and emergency unblinding. • Module 4 — Trial conduct: eligibility confirmation, randomisation, blinding integrity, and source documentation. Good Clinical Practice (GCP) certification is completed via an accredited course (e.g. a TransCelerate-recognised provider) and is additional to the above. Competency is confirmed by a supervised or simulated administration before the first live dose, with a documented refresher on protocol amendment or after prolonged inactivity.