Safety and Efficacy of Artesunate & Curcumin in Crohn's Disease

NCT04713631 | Unknown Phase 2

• 1 other identifier: 2020-37-EMP-114
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Crohn's Disease

Keywords

Crohn's Disease Activity Index (CDAI); Artesunate; Curcumin; Azathioprine

Outcome Measures

Primary Outcomes (1)

• Remission of disease

  Remission of disease as defined by a Crohn's Disease Activity Index (CDAI \< 150). The change in response will be studied by studying the change in CDAI after 1 week, 1 month, 3 months and 6 months

  Baseline to 6 months

Secondary Outcomes (4)

• Effect of artesunate and curcumin on azathioprine metabolites

  Baseline to 1 week

• Change in tumor necrosis factor-alpha

  baseline to 6 months

• Change in C-reactive protein

  baseline to 6 months

• Change in fecal calprotectin

  baseline to 6 months

Study Arms (4)

Artesunate and Curcumin

ACTIVE COMPARATOR

Artesunate 200 mg PO once a day x 2 weeks. Curcumin 2 gm PO once a day x 13 weeks.

Drug: Artesunate; Drug: Curcumin

Artesunate and Placebo C

ACTIVE COMPARATOR

Artesunate 200 mg PO once a day x 2 weeks. Placebo C x 13 weeks.

Drug: Artesunate; Drug: Placebo C

Curcumin and Placebo A

ACTIVE COMPARATOR

Placebo A x 2 weeks. Curcumin 2 gm PO once a day x 13 weeks.

Drug: Curcumin; Drug: Placebo A

Placebo A and Placebo C

PLACEBO COMPARATOR

Placebo A x 2 weeks. Placebo C x 13 weeks.

Drug: Placebo A; Drug: Placebo C

Interventions

Artesunate DRUG

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.

Artesunate and Curcumin; Artesunate and Placebo C

Curcumin DRUG

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

Artesunate and Curcumin; Curcumin and Placebo A

Placebo A DRUG

Artesunate looking placebo

Curcumin and Placebo A; Placebo A and Placebo C

Placebo C DRUG

Curcumin looking placebo

Artesunate and Placebo C; Placebo A and Placebo C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanjay Gandhi Postgraduate Institute of Medical Sciences: lead
• St George's University of London, London, UK: collaborator

Study Sites (1)

Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)

Lucknow, Uttar Pradesh, 226014, India

RECRUITING

Related Publications (3)

• Suskind DL, Wahbeh G, Burpee T, Cohen M, Christie D, Weber W. Tolerability of curcumin in pediatric inflammatory bowel disease: a forced-dose titration study. J Pediatr Gastroenterol Nutr. 2013 Mar;56(3):277-9. doi: 10.1097/MPG.0b013e318276977d.

  PMID: 23059643 BACKGROUND

• Hou L, Huang H. Immune suppressive properties of artemisinin family drugs. Pharmacol Ther. 2016 Oct;166:123-7. doi: 10.1016/j.pharmthera.2016.07.002. Epub 2016 Jul 10.

  PMID: 27411673 BACKGROUND

• Yang Z, Ding J, Yang C, Gao Y, Li X, Chen X, Peng Y, Fang J, Xiao S. Immunomodulatory and anti-inflammatory properties of artesunate in experimental colitis. Curr Med Chem. 2012;19(26):4541-51. doi: 10.2174/092986712803251575.

  PMID: 22834815 BACKGROUND

MeSH Terms

Conditions

Crohn Disease

Interventions

Artesunate; Curcumin

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Diarylheptanoids; Heptanes; Alkanes; Hydrocarbons, Acyclic; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Uday C Ghoshal

  Medical council of India, Association of Indian Universities

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Uday C Ghoshal

CONTACT

2494405; udayghoshal@gmail.com

Devinder Kumar

CONTACT

kumardkd@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: January 19, 2021
• Study Start: January 21, 2021
• Primary Completion: December 1, 2023
• Study Completion: January 1, 2024
• Last Updated: May 23, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)