Using statins to modify gut bacteria in ulcerative colitis patients

Drug Repurposing - Statins as Microbiota Modulating Agents in Ulcerative Colitis

This study is testing if the cholesterol-lowering drug Rosuvastatin can change gut bacteria in people with ulcerative colitis to see if it helps reduce inflammation and improve their symptoms.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Universitaire Ziekenhuizen KU Leuven (other)
• Drugs / interventions: prednisone
• Locations: 2 sites (Bonheiden, Antwerp and 1 other locations)
• Trial ID: NCT04883840 on ClinicalTrials.gov

What this trial studies

This study evaluates the potential of statins, specifically Rosuvastatin, to modulate the microbiota in individuals with ulcerative colitis and healthy volunteers. It focuses on altering the inflammation-associated microbiota profile known as Bacteroides2 (Bact2) and assesses the impact of these changes on disease activity and inflammatory parameters in ulcerative colitis patients. Participants will be monitored for their microbiota composition and clinical outcomes over the course of the intervention.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 70 with mild to moderate active ulcerative colitis or in remission, who have the specific Bact2 microbiota profile.

Not a fit: Patients with a history of statin use, active liver disease, or significant gastrointestinal surgeries may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to new treatment strategies for managing ulcerative colitis by leveraging the microbiome.

How similar studies have performed: While the use of statins for microbiota modulation is a novel approach, previous studies have explored microbiome-targeted therapies in inflammatory bowel diseases with varying degrees of success.

Eligibility criteria

Inclusion Criteria:

* General criteria

  * Bact2 enterotyped one month before start of study intervention (at least 150 of enrolled participants must meet this criteria)
  * Willingness to participate in the study and to sign the informed consent (Dutch)
  * Between 18 and 70 years old
  * Access to a -20°C freezer Criteria specific to UC patients
  * Patients in remission (mayo score below 4) or with currently mild to moderate active ulcerative colitis (defined by Mayo score of 4-10), despite stable medication (8 weeks) and a Mayo endoscopic sub-score 2- 3 at week 0 Criteria specific to healthy Bact2 participants
  * Individuals with no physician diagnosed diseases or disorders

Exclusion Criteria:

* General criteria

  * Prior and/or ongoing use of statins before study start
  * History of surgical intervention in gastrointestinal tract (appendectomies are allowed)
  * Females who are pregnant or actively trying to become pregnant
  * Individuals with active liver disease including unexplained persistent elevations of serum transaminases and any serum transaminases elevation exceeding three times the upper limit of normal (ULN)
  * Lactose intolerance
  * Pre-diabetic participants
  * Personal or family history of hereditary muscular disorders
  * Individuals with a history of or diagnosed with alcohol abuse Criteria specific to UC patients
  * Other conditions leading to profound immunosuppression such as HIV, infectious diseases leading to immunosuppression, bone marrow malignancies, liver cirrhosis
  * A diagnosis of Crohn's disease or indeterminate colitis
  * Individuals with hypothyroidism
  * Individuals with a diagnosis of diabetes mellitus
  * Individuals with severe renal impairment (creatinine clearance \<30 ml/min)
  * Individuals with myopathy
  * Participants who have taken antibiotics sometime in the past four months
  * Use of antibiotics one month prior to week 0
  * Steroid dependency and requiring \>16mg Medrol (methyl prednisone) or equivalent two week before week 0 Criteria specific to healthy Bact2 participants
  * Participants with family history of autoimmune chronic inflammatory diseases like multiple sclerosis, IBD, and rheumatoid arthritis

Where this trial is running

Bonheiden, Antwerp and 1 other locations

• Imelda Ziekenhuis — Bonheiden, Antwerp, Belgium (NOT_YET_RECRUITING)
• UZ Leuven — Leuven, Vlaams-Brabant, Belgium (RECRUITING)

Study contacts

• Principal investigator: Severine Vermeire, MD & PhD — KU/UZ Leuven
• Study coordinator: Tanine Daryoush, MS

Conditions: Ulcerative Colitis, Microbiome, Dysbiosis