Efficacy of Oral Rifaximin on Intestinal Barrier Integrity and Inflammatory Signaling in Patients with Opioid Use Disorder: A Multicenter Clinical Trial
- Trial ID
- 2025-524778-41-00
- Sponsor
- Fondazione Santa Lucia
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to determine the effect of 4 weeks of rifaximin administration compared to placebo on intestinal barrier integrity and gut-derived inflammatory signalling in patients with opioid use disorder. This investigation aims to assess the potential of modulating the microbiota–gut–brain axis to address physiological disruptions associated with substance use disorder. Secondary objectives include:
- Evaluation of the impact of rifaximin on systemic inflammatory biomarkers related to intestinal barrier disruption.
- Assessment of whether biological modulation of intestinal permeability and inflammatory signalling correlates with changes in cue-induced opioid craving.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of individuals diagnosed with opioid use disorder according to DSM-5 criteria. Eligible participants include both males and females between the ages of 18 and 60 years. For female participants, pregnancy and lactation are exclusion criteria. The cohort includes individuals in the early phase of withdrawal or those undergoing treatment to discontinue opioid use. Preference is given to patients experiencing recent abstinence, specifically within 1 to 4 weeks from the last use, excluding those in uncontrolled acute withdrawal. Individuals receiving methadone maintenance treatment are eligible if they maintain a stable dose throughout the first month of the study.
Plans and Procedures
This phase 4, multicenter clinical trial is designed to evaluate the effects of oral rifaximin compared to a placebo in patients diagnosed with opioid use disorder. The methodology utilizes a randomized and double-blind design to assess improvements in intestinal barrier integrity and gut-derived inflammatory signaling. Following an initial screening visit to confirm eligibility based on DSM-5 criteria, participants undergo a 4-week treatment period. The study evaluates primary efficacy endpoints including the intensity of opioid craving, indicators of social isolation, and the tapering of methadone therapy. Secondary endpoints involve the measurement of intestinal permeability, fecal microbiota characteristics, and the monitoring of adverse events. Participant involvement is structured around the treatment duration and subsequent follow-up assessments to monitor clinical outcomes and safety.
Treatment
The investigational medicinal product is rifaximin, administered as a film-coated tablet. The dosage is 800 mg via the oral route. This treatment is intended for use in patients with opioid use disorder.
The placebo consists of a film-coated oral tablet containing no active pharmaceutical ingredient. It is composed exclusively of pharmaceutical excipients with established safety profiles. The placebo is designed to be comparable in appearance, administration, and handling to the rifaximin tablets to maintain blinding throughout the clinical trial.
Efficacy
The assessment of efficacy in this clinical trial focuses on the evaluation of opioid use disorder. The primary efficacy endpoints consist of the measurement of opioid craving intensity, indicators of social isolation or disconnection, and the tapering of methadone therapy.
Secondary endpoints involve the assessment of improvements in intestinal permeability, fecal microbiota characteristics, adverse events, and infections. The investigation aims to determine the impact of 4 weeks of treatment on intestinal barrier integrity and gut-derived inflammatory signalling.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Diagnosis of OUD according to DSM‑5 criteria; patients in the early phase of withdrawal or in treatment with the intention to discontinue opioid use; age between 18 and 60 years; for female participants, not pregnant and not breastfeeding; ability to understand and sign informed consent. Patients with recent abstinence (e.g., within 1–4 weeks from last opioid use) will be preferentially included to capture the early adaptation phase, but not those in uncontrolled acute withdrawal. Patients receiving methadone maintenance treatment are eligible, provided they are on a stable dose and willing not to modify it for at least the first month of the study.
Exclusion Criteria
- Presence of known organic gastrointestinal diseases (e.g., Crohn’s disease, ulcerative colitis, untreated celiac disease, advanced-stage liver cirrhosis, GI malignancies) that may significantly alter intestinal permeability or contraindicate biopsy; diagnosis of active chronic infection; severe uncontrolled medical conditions; active psychiatric disorders that impair cooperation; current use of antibiotics or probiotics that significantly alter the microbiota (requiring at least a 4‑week washout before the study); HIV/AIDS or immunocompromised status; known allergy or severe adverse reaction to rifaximin or to antibiotics of the rifamycin class; for women, confirmed or planned pregnancy during the study period. Concurrent participation in other interventional clinical trials; inability to comply with study procedures.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Yet Recruiting | 15 Mar 2026 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Normix 200 mg compresse rivestite con film | Test | COMPRESSE RIVESTITE CON FILM | ORAL | 800 | 4 | PRD11412027 |
The placebo is a film-coated oral tablet designed to be comparable in appearance, administration, and handling to the investigational medicinal product (rifaximin 200 mg film-coated tablets), while containing no active pharmaceutical ingredient. The placebo consists exclusively of commonly used pharmaceutical excipients with established safety profiles and is administered solely to maintain blinding in the clinical trial. | Placebo | N/A | — | — | — | N/A |