Boosting Biologics in UC

Study Overview
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Brief Summary
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This study evaluates the safety of the probiotic compound IDOFORM TRAVEL® in patients with ulcerative colitis undergoing anti-TNF treatment with insufficient clinical response. Furthermore, the study aims to explore the composition of the bacteria of the gut as well as the immunological activity in patients with ulcerative colitis undergoing anti-TNF treatment, aiming to identify differences between groups of patients responding and not responding adequately to treatment. The project will explore whether probiotics have beneficial effects as adjuvant therapy in ulcerative colitis patients with insufficient response to anti-TNF treatment.

Detailed Description
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The use of anti TNF agents has improved the medical treatment of ulcerative colitis (UC). However, one third of patients receiving such treatment will not reach remission. Studies have demonstrated that the gut microbiome influences the cytokine response and in particular the TNF production. In this study we aim to manipulate the gut microbiome in patients with ulcerative colitis not responding to anti-TNF therapy to evaluate potential beneficial effects. 20 UC patients with insufficient response to anti-tumor necrosis factor (anti-TNF) therapy upon routine evaluation colonoscopy 6-12 months after start of treatment will receive intervention with the probiotic formula IDOFORM Travel®, 4 capsules daily for 8 weeks. A colonoscopy will be performed at baseline (week 0) and after intervention (week8). Gut biopsies, fecal samples and serological markers will, in addition to clinical examination and endoscopic results, be used to evaluate the safety and possible beneficial effects of the intervention. In a subsidiary cross-sectional study, 20 UC patients on anti-TNF therapy in remission upon evaluation colonoscopy will serve as controls. 20 individuals with no history of inflammatory bowel disease will be recruited as healthy controls.

Official Title
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Boosting Biologics in Ulcerative Colitis

Conditions
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Ulcerative Colitis, Inflammatory Bowel Diseases

Intervention / Treatment
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* Dietary Supplement: IDOFORM®Travel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects may be included as cases in the study if they meet all of the following criteria: Diagnosed With ulcerative colitis based on Lennard-Jones criteria Under treatment With anti-TNF infusions/injections defined as infliximab or adalimumab Failure to Reach remission upon routine evaluation colonoscopy after 6-12 months of treatment - defined as an endoscopy sub score of ≥ using the Mayo score for ulcerative colitis Age 18-75 Signed informed consent and expected Cooperation of the patients for the treatment and follow up must be obtained and documented according to International Committee on Harmonization (ICH) Good Clinical Practice (GCP), and national/local regulations. Subjects may be included as Control subjects in the sub-study if they meet all of the following criteria: Diagnosed With ulcerative colitis based on Lennard-Jones Criteria Under treatment With anti-TNF infusions/injections defined as infliximab or adalimumab Remission upon routine colonoscopy after 6-12 months of treatment - defined as an endoscopy sub score of ≤ using the Mayo score for ulcerative colitis Age 18-75 Signed informed consent and expected Cooperation of the patients for the treatment and follow up must be obtained and documented according to International Committee on Harmonization (ICH) Good Clinical Practice (GCP), and national/local regulations. OR if they meet all the following criteria: No history of inflammatory bowel disease Age 18-75 Signed informed consent and expected Cooperation of the patients for the treatment and follow up must be obtained and documented according to International Committee on Harmonization (ICH) Good Clinical Practice (GCP), and national/local regulations. Exclusion Criteria: Clinical status poor to such extent that treating physician finds refraining from escalation of treatment contraindicated Signs of severe ulcerative colitis as defined by the Montreal classification of severity of ulcerative colitis = 3: Passage of at least six bloody stools daily, pulse rate of at least 90 beats per minute, temperature of at least 37.5°C, haemoglobin of less than 10.5 g/100 ml, and erythrocyte sedimentation rate (ESR) of at least 30 mm/h. Previous use of anti-TNF medication History of bowel resection, other inflammatory bowel disease (IBD)-related surgery, or other major intestinal surgery Plasma hepatitis C (HCV) positive Serum hepatitis B surface antigen (HBsAg) positive HIV positive Comorbidity of coeliac disease or malnutrition Pregnancy Concomitant use of non-steroid anti-inflammatory drugs (NSAIDS) or corticosteroids Concomitant use of antithrombotic pharmaceutical substances Regular (weekly) use of any probiotic substance within 3 months prior to inclusion Use of antibiotics within 3 months prior to inclusion Deranged liver function (serum albumin < 25 g/L or Child-Pugh ≥10) Renal failure (estimated glomerular filtration rate (eGFR) < 30 Heart failure (NYHA class II-IV) Any reason why, in the opinion of the investigator, the patient should not participate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention with probiotics<br>Intervention with the probiotic compound IDOFORM®Travel. The patient will receive four capsules orally every 24 hour (12*10^9 cfu/day) for eight weeks as adjuvant therapy to his/her anti-TNF treatment. The intervention arm will at the end of intervention serve as their own controls compared to baseline data (before intervention). | Dietary Supplement: IDOFORM®Travel<br>* Four capsules IDOFORM®Travel orally every 24 hour (12*10^9 cfu/day) for eight weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Unit of Measure: Frequency | 8 weeks | 
| Total Mayo Score for Ulcerative Colitis | Alterations in Total Mayo Score at time of control colonoscopy. Minimal value=0 (best outcome), Maximal value = 12 (worst outcome) | 8 weeks | 
| Change in Fecal Calprotectin | Change in Fecal Calprotectin from baseline (week 0) to end of intervention (week 8) and after intervention (week 12). Unit of measure: mg/kg | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alterations in mucosa-adherent microbial composition | Exploratory analyses of microbial composition at baseline (week 0) and at end of intervention (week 8). (Unit of Measure: Descriptive) | 8 weeks | 
| Alterations in epithelial gene expression | Exploratory (Unit of Measure: Descriptive) | 8 weeks | 
| Alterations in markers of chronic inflammation / immune activation | Explorative (Unit of Measure: Descriptive) | 8 weeks |