Clinical trial NCT04883840: Drug Repurposing - Statins as Microbiota Modulating Agents in Ulcerative Colitis
Official title: Drug Repurposing - Statins as Microbiota Modulating Agents in Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Ulcerative Colitis
Keywords: Microbiome
Dysbiosis
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Vlaams Instituut Biotechnologie (VIB)
First posted: 2021-05-12
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: * 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


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

Primary outcomes:
measure: UC Mayo Score
timeFrame: 8 weeks
measure: Systemic inflammatory measures
timeFrame: 8 weeks
measure: Local inflammatory measures
timeFrame: 8 weeks
Secondary outcomes:
measure: Significant change in gastrointestinal microbiome composition
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis
state: Antwerp
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-Brabant
Study officials:
affiliation: KU/UZ Leuven
name: Severine Vermeire, MD & PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: KU Leuven/VIB
name: Jeroen Raes, PhD
role: STUDY_DIRECTOR
References: