E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
There are two population groups, 20 healthy volunteers and at least 165 individuals diagnosed with IBD. Either with remission to mild/moderate active ulcerative colitis or remission to mild Crohn's disease. |
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E.1.1.1 | Medical condition in easily understood language |
A bowel disease that are characterized by inflammation with ulcer formation in the lining of large intestine (UC) and/or rest of intestines (CD). Characterized by diarrhea and abdominal cramps.
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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 inflammatory bowel disease patients. |
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E.2.2 | Secondary objectives of the trial |
• Evaluation of the effect of microbiota modulation on disease activity in ulcerative colitis and Crohn's disease patients. • Evaluation of reduced inflammatory parameters of participants involved in trial
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
General criteria •Willingness to participate in the study and to sign the informed consent (Dutch) •Between 18 and 75 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 Criteria specific to CD patients • Patients in clinical remission (CDAI score below 150 at week 0) or with currently mild active Crohn’s disease (CDAI score between 150–220 at week 0), despite stable medication
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E.4 | Principal 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 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
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the trial is modulate at least 15% of those with Bact2 enterotype to a different enterotype and breaking the inflammatory cycle between the IBD and pro-inflammatory microbes. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Either at study site visit after the first period (week 8 + or - 3 days) or the second period (week 16 + or - 3 days) of intervention is complete. This depends whether the participant was randomized into the placebo or IMP first arms. |
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E.5.2 | Secondary end point(s) |
To ensure that a significant number of ulcerative colitis participants improved in their disease state, a reduction of at least 1 point in their mayo endoscopic sub score and/or a general 3-point reduction of their total Mayo score. For Crohn’s disease patients, a significant improvement is characterized by a 70-point reduction in the Crohn’s disease activity index (CDAI) or a CDAI score < 150 points Inflammatory status local (faecal calprotectin) and systemically (hs-CRP) will be closely assessed in addition to other health parameters. Time point comparisons of these variables will be conducted with paired Wilcoxon tests with multiple testing correction. Mental outlook and response to treatment versus outlook with placebo, characterized by the RAND-36 in questionnaires will be conducted with fisher exact tests. Other lifestyle habits and alterations will be documented with questionnaires and used to account for confounders in the analyses. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints at study site visit after the first period (week 8 + or - 3 days) or the second period (week 16 + or - 3 days) of intervention is complete when the IBD patient enters the study site for their evaluation. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |