Curcumin Supplementation as an Add on Treatment for Patients With Inflammatory Bowel Diseases Treated With Vedolizumab

Study Overview
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Brief Summary
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Introduction: The pathogenesis of inflammatory bowel diseases (IBD) is characterized by dysregulation of the innate immune response it's associated with Th1, Th17 up-regulation, reflected by increased cytokine secretion including TNF-α. A main effective therapeutic interventions is blocking TNFα. Vedolizumab, an anti integrin, is a new class of treatment designed to block trafficking of lymphocytes in the gut. Clinical trials and real life experience response rates at week 6 range between 30-45%. Curcumin suppresses NFκβ levels via alteration of TLR2/4 pathways lowering TNF-α upstream. Curcumin is safe and efficacious in inducing response and remission in mild-moderate Ulcerative colitis (UC) and maintaining remission when used as an add-on to 5ASA derivatives, only with strict adherence to treatment overtime. Objectives: Facing the low rate of response to therapies in IBD, the need for new treatments and the use of combination strategies lead us to believe that combining vedolizumab and curcumin may have a synergistic effect and will enable optimal immunomodulation. Hypothesis: Concomitant oral curcumin in IBD patients with colonic involvement will augment remission rates as well as clinical and biochemical response. Type of research and methods of data collection: A randomized controlled trial in 84 adults with colonic IBD (UC and CD). Eligible patients are during vedolizumab induction, patients will randomized will be into curcumin or placebo. Data will managed by investigators.

Official Title
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Curcumin Supplementation as an Add on Treatment for Patients With Inflammatory Bowel Diseases Treated With Vedolizumab

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Dietary Supplement: Curcumin
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established inflammatory bowel disease Age ≥18 years old At inclusion all patients must have a documented active colonic involvement based on either endoscopy or imaging: Commencing vedolizumab therapy according to the treating physician or on active therapy up to 6-weeks. Active luminal disease: CD- HBI ≥325, 26 UC- partial Mayo ≥227 Evident active disease on endoscopy or imaging within 2-week from inclusion or elevated inflammatory markers at screening (CRP> 0.5 mg/dl, or fecal calprotectin>100 μgr/gr stool or ESR >40). Exclusion Criteria: CD- isolated small bowel disease (L1) UC- proctitis (E1) Perianal disease Pregnancy Biliary obstruction Concomitant treatment with beta blockers, anti-coagulants, and norfloxacin (relative contra indications to curcumin therapy). Curcumin supplementations within the last 6 months.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active<br>4 gr Curcumin daily for 1 year in addition to vedolizumab 300 mg per infusion (standard of care) | Dietary Supplement: Curcumin<br>* 4 gr curcumin<br>|
| Placebo Comparator: Sham<br>4 gr placebo daily for 1 year in addition to vedolizumab300 mg per infusion (standard of care) | Dietary Supplement: Placebo<br>* 4 gr placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission- Crohn's disease patients | Crohn's disease patients - disease activity indexe: Harvey Bradshow index (HBI) less that 3 | 52 weeks | 
| Clinical remission- ulcerative colitis patients | Disease activity index - partial Mayo score less than 2 | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease response- Crohn's disease patients | Disease activity index- Harvey Bradshow index (HBI ) a drop of 3 points | 52 weeks | 
| Disease response- ulcerative colitis patients | Disease activity index -partial Mayo score a drop of 2 points | 52 weeks | 
| Biochemical remission | Fecal calprotectin less than 150 µg/gr | 52 weeks | 
| Biochemical remission | C reactive protein (CRP) less thn 0.5 mg/dl | 52 weeks |