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

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.

Study Overview

• Status: Unknown
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Dietary supplement: Curcumin; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Petah tikva, Israel
    • Recruiting
    • Rabin Medical Center
    • Contact: Henit Yanai, MD
    • Contact: Tamar Pfefer Gic, MA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Established inflammatory bowel disease
2. Age ≥18 years old
3. At inclusion all patients must have a documented active colonic involvement based on either endoscopy or imaging:
4. Commencing vedolizumab therapy according to the treating physician or on active therapy up to 6-weeks.

5. Active luminal disease:

   CD- HBI ≥325, 26 UC- partial Mayo ≥227

6. 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:

1. CD- isolated small bowel disease (L1) UC- proctitis (E1)
2. Perianal disease
3. Pregnancy
4. Biliary obstruction
5. Concomitant treatment with beta blockers, anti-coagulants, and norfloxacin (relative contra indications to curcumin therapy).
6. Curcumin supplementations within the last 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active; 4 gr Curcumin daily for 1 year in addition to vedolizumab 300 mg per infusion (standard of care)	Dietary supplement: Curcumin; 4 gr curcumin
Placebo Comparator: Sham; 4 gr placebo daily for 1 year in addition to vedolizumab300 mg per infusion (standard of care)	Dietary supplement: Placebo; 4 gr placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Henit Yanai
• Collaborators: Shaare Zedek Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: June 14, 2017
• First Submitted That Met QC Criteria: April 9, 2018
• First Posted (Actual): April 18, 2018

Study Record Updates

• Last Update Posted (Actual): October 9, 2020
• Last Update Submitted That Met QC Criteria: October 7, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Curcumin
• Other Study ID Numbers: RMC-0290-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No