Clinical trial

Phase 2a Randomised Double-blind Placebo-controlled Trial to Assess Safety, Efficacy of Artesunate & Curcumin in Crohn's Disease Patients, Who Continue to Have Mild to Moderate Disease Activity on an Adequate Dose of Azathioprine

Name

2020-37-EMP-114

Description

This is a single center phase 2a, randomised double-blind, placebo-controlled factorial design, proof of concept trial. Patients with Crohn's disease who are on an adequate dose of azathioprine and still continue to active disease (CDAI \> 150 and c-reactive protein \> 6) will be enrolled. Forty patients will be randomised in a 1:1:1:1 ratio into 4 groups in a 2x2 factorial design to receive artesunate 200 mg PO daily for 2 weeks and / or Curcumin 2 gm PO daily for 3 months or placebo. Treatment Curcumin x 13 weeks Placebo C x 13 weeks Artesunate x 2 weeks Group 1 Group 2 Placebo A x 2 weeks Group 3 Group 4 During the treatment period and follow up period patients will be continued on their regular dose of azathioprine and 5-aminosalicylic acid with no change allowed during the study period. Patients will maintain a daily diary of symptoms and adverse events. Scheduled hospital visits with blood and stool tests will be at baseline, week 1, month 1, month 3 and month 6. Primary endpoint will be remission (defined as CDAI \< 150) at 3 months

Trial arms

Trial start

2021-01-21

Estimated PCD

2023-12-01

Trial end

2024-01-01

Status

Recruiting

Phase

Early phase I

Treatment

Artesunate

Artesunate is approved for the treatment of malaria and is on the World Health Organization list of Essential Medicines. Artesunate has a hemisuccinate group which confers substantial water-solubility and high oral bioavailability and therefore a convenient oral route of administration. Artesunate has a good safety and tolerability profile, having been used to treat millions of adults and children globally.

Arms:

Artesunate and Curcumin, Artesunate and Placebo C

Curcumin

Curcumin has been used in Indian cuisine and traditional medicine for centuries. It has low solubility in aqueous solution and yields low serum levels following oral administration. In the setting of inflammatory bowel disease where the required site of action is the bowel, systemic absorption may be less relevant. Curcumin and its reduced metabolites undergo conjugation in the liver. Curcumin has a half life of 6-7 hours. It has been found to be safe at oral doses of 2 gm and 3 gm a day in patients with ulcerative colitis, for up to 1 year. In a dose titration study conducted in children with inflammatory bowel disease 2 gm twice daily of curcumin was well tolerated

Arms:

Artesunate and Curcumin, Curcumin and Placebo A

Placebo A

Artesunate looking placebo

Arms:

Curcumin and Placebo A, Placebo A and Placebo C

Placebo C

Curcumin looking placebo

Arms:

Artesunate and Placebo C, Placebo A and Placebo C

Size

Primary endpoint

Remission of disease

Baseline to 6 months

Eligibility criteria

Inclusion Criteria: * Men or women with a diagnosis of Crohn's disease who are being treated with an adequate, constant dose of azathioprine for at least 3 months (adequate dose is 1 mg/kg in those with low Thiopurine methyltransferase, 2 mg per kg in those with normal Thiopurine methyltransferase) * Age 18 to 65 yrs * Crohn's disease of mild to moderate activity (CDAI 150 to 450) and c-reactive protein \> 6 * Hemoglobin \>9, white blood cells \> 3500, platelets \> 1,00,000 * Bilirubin \< 3, alanine transaminase \< 3x upper limit of normal * Glomerular filtration rate \>45 * Normal electrocardiogram Exclusion Criteria: * Pregnancy, women who are planning to get pregnant and those unwilling to use contraception * Lactation * Bowel surgery with the past 3 months * Intra-abdominal abscess * Ileostomy or colostomy * Change in dose of 5-aminosalicylic acid in the past 4 weeks * Use of corticosteroids within the past 4 weeks

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'FACTORIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'maskingDescription': 'double-blind', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 40, 'type': 'ESTIMATED'}}

Updated at

2023-05-23

1 organization

3 products

1 indication

Organization

Sanjay Gandhi Postgraduate Institute of Medical Sciences

Product

Indication

Product

Product