Curcumin + Aminosalicylic Acid (5ASA) Versus 5ASA Alone in the Treatment of Mild to Moderate Ulcerative Colitis (5ASA)

Randomized, Double-blind, Placebo-controlled Study to Evaluated the Efficacy of Combining Curcumin+5ASA Medication Versus 5ASA Medication Alone on Active Mild to Moderate Ulcerative Colitis Patients

Ulcerative colitis (UC) is a chronic inflammatory disease resulting in increased morbidity in patients. The current standard treatment for mild to moderate UC (MTMUC) includes 5-aminosalicylic compounds (5ASA) such as olsalazine and mesalamine, yet some patients continue to experience disease symptoms and flare-ups. These patients require higher dosages of 5ASA medications and in many cases escalate to steroid and/or immunosuppressant therapy which comprises higher risk of hazardous side effects.

Curcumin, an active ingredient of the Indian herb Rhizoma Curcuma Longa, has been extensively studied in the context of inflammatory diseases. In humans, a controlled study using curcumin as an adjusted therapy to 5ASA medication has shown it to be superior to placebo in maintaining remission in MTMUC patients . A small, preliminary open label study has also shown efficacy in reducing disease symptoms and inflammatory markers in this group of patients .

This data provides bases for investigating an integrative approach to optimize the current standard treatment in MTMUC patients. We speculate that using a combined therapy of 5ASA medication and curcumin could benefit this subgroup of patients and reduce morbidity and perhaps need for escalating pharmacological intervention.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Dietary supplement: Curcumin; Drug: 5-aminosalicylic acid

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel
    • Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of UC as confirmed by endoscopic or histologic criteria as established by RomeIII
• Disease activity score of >5 and ≤13 according to the Simple clinical colitis activity index (SCCAI)
• Patient on stable 5 ASA medication dose for at least 4 weeks prior to inclusion
• Patients who receive immunosuppressant or biological therapy (azathioprine, 6-mercaptopurine, infliximab or methotrexate) must be on stable dose for at least 3 months prior to inclusion
• Patients who receive topical therapy (5ASA or steroidal), must be on stable dose for a least 2 weeks prior to inclusion
• Patient had hemoglobin of >10 g/dl.
• Able and willing to give written consent

Exclusion Criteria:

• Patient with renal or liver disease, sever cardiovascular disease, chronic pancreatitis, diabetes mellitus or gallstone.
• Patient with laboratory abnormalities indicating anemia (hemoglobin <10), leucopenia, thrombocytopenia, abnormal coagulation.
• Patient with infection, sepsis or pneumonia.
• Pregnant or nursing women.
• Unable or unwilling to receive CURCUMIN therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatments arm; Patients allocated for this arm will receive 5ASA medication (as advised by their treating physician) + 3 capsules (total of 820 mg each,containing 500 mg curcumin ) curcumin twice daily after meals.	Dietary supplement: Curcumin; 3 capsules (820 mg containig 500 mg curcumin each) twice daily.; Drug: 5-aminosalicylic acid; The dosage of 5ASA medication will be the maximum dosage given in this group of patients according to clinical guidelines (4gr' per os + topical 1gr mesalamine; Other Names: Pentasa, Asacol, Rafasal, Mesalamine.
Placebo Comparator: Control arm; Patients allocated to this arm will receive 5ASA medication (as advised by their treating physician) + 3 capsules (820gr each) of placebo twice a day after meals.	Drug: 5-aminosalicylic acid; The dosage of 5ASA medication will be the maximum dosage given in this group of patients according to clinical guidelines (4gr' per os + topical 1gr mesalamine; Other Names: Pentasa, Asacol, Rafasal, Mesalamine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of patients who achieve clinical remission compared between the two study arms.	The percentage of patients who achieve clinical remission compared between the two study arms at week 4 after induction of therapy. Clinical remission is defined as score of ≤2 in the Simple Clinical Colitis Activity Index (SCCAI) .	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to response	Time to response (TTR) compared between study and control groups. Response is defined as remission or significant improvement. TTR is defined by number of days to achieve clinical response.	4 weeks
significant improvement	Percentage of patients that show significant improvement (drop of ≥3 points in SCCAI) compared between the two study arms at week 4 after induction of therapy.	4 weeks
serologic markers	Improvement in serologic parameters according to Seo index	4 weeks
Percentage of patient on corticosteroids or anti TNF treatment		4 weeks
improvement in endoscopic score	Improvement in endoscopic score compared to inclusion day (in subgroup of patients)	4 weeks
Improvement in IBD questionnaire (IBDQ).		4 weeks

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Principal Investigator: Alon Lang, MD, Sheba Medical Center; Principal Investigator: Nir Salomon, C.Ac, Sheba Medical Center

Publications and helpful links

General Publications

• Lang A, Salomon N, Wu JC, Kopylov U, Lahat A, Har-Noy O, Ching JY, Cheong PK, Avidan B, Gamus D, Kaimakliotis I, Eliakim R, Ng SC, Ben-Horin S. Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2015 Aug;13(8):1444-9.e1. doi: 10.1016/j.cgh.2015.02.019. Epub 2015 Feb 24.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: March 21, 2011
• First Submitted That Met QC Criteria: March 21, 2011
• First Posted (Estimate): March 22, 2011

Study Record Updates

• Last Update Posted (Estimate): February 12, 2016
• Last Update Submitted That Met QC Criteria: February 11, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Ulcerative colitis; Curcumin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; 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; Anti-Bacterial Agents; Antitubercular Agents; Mesalamine; Aminosalicylic Acid; Curcumin
• Other Study ID Numbers: SHEBA-10-8356-AL-CTIL