Curcumin for Prevention of Relapse in Patients With Ulcerative Colitis

Study Overview
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Brief Summary
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UC is a chronic inflammatory bowel disorder with relapsing and remitting course. The efficacy of mesalazine in preventing relapse in patients with UC is well-known and supported by randomized studies. However, mesalazine can be associated with side-effects. In addition, drug compliance is suboptimal, especially when disease is not active. Curcumin is a natural phytochemical derived from the Indian spice turmeric. It is widely used, has potent anti-inflammatory, anti-oxidant and anti-tumour properties. The aims of this double-blind, placebo-controlled randomized trial is to assess the efficacy of curcumin in the prevention of relapse in patients with ulcerative colitis (UC).

Detailed Description
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UC is a chronic inflammatory bowel disorder with relapsing and remitting course. The incidence of UC in Hong Kong has increased by 30-fold in the past three decades. The efficacy of mesalazine in preventing relapse in patients with UC is well-known and supported by randomized studies. However, mesalazine can be associated with side-effects. In addition, drug compliance is suboptimal, especially when disease is not active. Without mesalazine, the risk of relapse in UC in one year is approximately 60-70%. Repeated flares are disabling for the patient, and lead to increased hospitalisations, anatomical extension of disease, and increased cancer risk. In Hong Kong, 90 percent of patients with UC have low to medium compliance to mesalazine, and 50 percent would prefer the use of a complementary or alternative therapy to maintain disease remission. Identification of a natural product that is effective, acceptable, inexpensive and non-toxic remains an unmet need in patients with UC. Curcumin is a natural phytochemical derived from the Indian spice turmeric. It is widely used, has potent anti-inflammatory, anti-oxidant and anti-tumour properties. Preclinical studies in experimental animals showed that curcumin is effective in preventing colitis. We reported in a randomized study that curcumin is effective in the induction of remission in patients with mild to moderately active UC. Although curcumin is popular amongst patients with inflammatory bowel disease, its efficacy in maintaining disease remission in UC is uncertain. We propose a double-blind, placebo-controlled trial to assess the efficacy of curcumin in preventing clinical relapse in patients with UC. Patients will be randomised to 2 gram curcumin once daily or an equivalent placebo for 12 months. The primary outcome is the rate of clinical relapse at 12 months. Secondary outcomes include adverse events, endoscopic remission, fecal calprotectin levels and time to relapse. Because the use of curcumin is already popular in Asia, this important clinical question will not be a priority of pharmaceutical companies. If proven, this industry-independent trial will be a landmark study that identifies an alternative effective treatment to maintain disease remission in patients with UC. Regardless of the outcome, it will inform clinical practice and provide invaluable data to international guideline committees on the management of this chronic inflammatory disease. The aims of this double-blind, placebo-controlled randomized trial is to assess the efficacy of curcumin in the prevention of relapse in patients with ulcerative colitis (UC).

Official Title
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A Double-blind, Randomized, Placebo-Controlled Trial of Curcumin Versus Placebo for Prevention of Relapse in Patients With Ulcerative Colitis

Conditions
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Ulcerative Colitis in Remission

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: in clinical remission for at least 1 month, defined as Mayo bowel frequency subscore ≤ 1 and Mayo rectal bleeding subscore = 0 (Table 2). a history of at least one flare with symptoms that required intervention within 24 months before screening age ≥ 18 written informed consent obtained Exclusion Criteria: receipt of immunosuppressive drugs or corticosteroids within 60 days of screening prior bowel surgery except appendectomy with severe relapse (Mayo score 9-12) in the last 3 months History or evidence of incompletely resected colonic mucosal dysplasia on regular curcumin supplements or intake of curry in diet for ≥5 days each week presence of infections (exclude simple infections such as influenza, etc.) or sepsis pregnancy or lactating women with a Mayo endoscopic subscore ≥2 on sigmoidoscopy or colonoscopy at baseline allergic to curry-related products

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Curcumin<br>Dietary supplements of Curcumin capsules | Dietary Supplement: Curcumin<br>* 3g of Curcumin per day<br>* Other names: Turmeric;|
| Placebo Comparator: Curcumin Placebo<br>Identical looking placebo of the active arm | Drug: Placebo<br>* 3g of Curcumin Placebo per day<br>* Other names: Curcumin placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The relapse rate at 12 months | Defined as clinical symptoms (increased bowel frequency with a bowel frequency Mayo subscore ≥ 1 or rectal bleeding with a Mayo rectal bleeding subscore ≥ 1) together with endoscopic evidence of active disease (Mayo endoscopic subscore ≥ 2). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | The severity grading of AEs will be assessed as Grade 1, 2, 3, 4 or 5 using the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Grading Scale, which can be found at: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf | 1 year | 
| Endoscopic remission | Defined as a mayo endoscopic subscore of 0 or 1 | 1 year | 
| Simple Clinical Colitis Activity Index (SCCAI) | compare the scores in two groups | 1 year | 
| Fecal calprotectin levels at 12 months | compare the difference of the levels between groups | 1 year | 
| Fecal immunochemical test (FIT) at 12 months | compare the positivity rate in those with flare | 1 year | 
| Quality of Life assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) | compare the scores in two groups | 1 year | 
| Patient Reported Outcomes (PRO) Questionnaire | The questionnaire will ask during the study follow up about the psychological aspects of UC patients, the baseline and score on final visit will be compared, as well as between the two groups | 1 year | 
| Pharmacokinetics study to measure the drug concentration-time courses | compare the absorption rate in two groups and to establish and evaluate the relationships and subsequently describe the effect-time courses of curcumin absorption in blood and colon. | 1 year |