Drug Repurposing - Statins as Microbiota Modulating Agents in Ulcerative Colitis

Study Overview
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Brief Summary
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Evaluation of the microbiota modulation away from inflammation associated microbiota profile Bacteroides2 (Bact2) Evaluation of the microbiota modulation potential of statins in Bact2- enterotyped, healthy volunteers and ulcerative colitis patients. Evaluation of the effect of microbiota modulation on disease activity in ulcerative colitis patients. Evaluation of reduced inflammatory parameters of participants involved in trial

Official Title
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Drug Repurposing - Statins as Microbiota Modulating Agents in Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Rosuvastatin 10mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Rosuvastatin 10mg<br>* Daily dose of one medication over 8 week period then switch to another medication over an 8 week period (type of medication during each intervention period is blinded and then randomized).<br>|
| Experimental: Rosuvastatin 10 mg<br> | Drug: Rosuvastatin 10mg<br>* Daily dose of one medication over 8 week period then switch to another medication over an 8 week period (type of medication during each intervention period is blinded and then randomized).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UC Mayo Score | Decrease P partial mayo by one point or stays in remission during experimental intervention when taking IMP | 8 weeks | 
| Systemic inflammatory measures | significant and substantial change in hs-CRP when taking IMP | 8 weeks | 
| Local inflammatory measures | significant and substantial change fecal calprotectin when taking IMP | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Significant change in gastrointestinal microbiome composition | Change away from dysbiotic enterotype to eubiotic one when taking IMP | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbiome, Dysbiosis