Chemopreventive Effect of Combination of Celecoxib and Metformin in Patients With Familial Adenomatous Polyposis

NCT06545526 | Recruiting Phase 3 DMC

• 1 other identifier: 4-2024-0371
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Familial adenomatous polyposis (FAP) leads to adenomas and eventual adenocarcinomas in colon and less frequently, duodenum. Chemopreventive strategies have been studied in FAP patients to delay the development of adenomas and cancers. The non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitor have shown the regression of colorectal and duodenal adenomas in FAP patients. However, these drugs showed gastrointestinal damage and cardiovascular risks, and new preventive strategies are needed. Metformin, an anti-diabetic drug, has recently been suggested to have a suppressive effect on tumorigenesis via inhibition of mTOR pathway, and have an inhibitory effect on polyp recurrence after removal of sporadic colorectal polyps. In addition, metformin has a number of potential mechnisms of carciovascular bebefit. We devised a randomized, open-label, comparative study to evaluate the effect of combination of celecoxib and metformin on polyps of colorectum and duodenum in FAP patients.

Conditions

Familial Adenomatous Polyposis

Outcome Measures

Primary Outcomes (1)

• Mean percentage change of the number and size of polyps in colon and/or duodenum.

  At the base-line endoscopy (colonoscopy and upper gastrointestinal endoscopy), india-ink tattoo will be placed in the ascending colon, sigmoid colon/rectum, and duodenum. In case of patient with retained rectum after colectomy and ileorectal anastomosis, sigmoidoscopy will be peformed. The base-line and six-month endoscopic examination will be recorded, and photographs will be taken at the tattoo-marked area and used for measurements of the number and size of polyps. The diameter of a polyp will be measured with the aid of biopsy forceps included in the photographic field, and only distinct polyps at least 2 mm in diameter will be counted.

  After six-month administration of celecoxib monotherapy or combination of celecoxib and metformin

Secondary Outcomes (1)

• A qualitative assessment of the total extent of colorectal and duodenal polyposis

  After six-month administration of celecoxib monotherapy or combination of celecoxib and metformin

Study Arms (2)

celecoxib monotherapy

ACTIVE COMPARATOR

celecoxib \[400mg, twice a day\] for 6 months

Drug: celecoxib monotherapy

celecoxib and metformin combination

EXPERIMENTAL

celecoxib \[400mg, twice a day\] and metformin \[1g, twice a day\] for 6 months

Drug: celecoxib and metformin combination

Interventions

celecoxib monotherapy DRUG

Patients will be randomly assigned in a 1:1 ratio to receive celecoxib monotherapy or combination of celecoxib and metformin orally for 6 months: celecoxib \[400mg, twice a day\] in arm 1, celecoxib \[400mg, twice a day\] and metformin \[1g, twice a day\] in arm 2.

celecoxib monotherapy

celecoxib and metformin combination DRUG

Patients will be randomly assigned in a 1:1 ratio to receive celecoxib monotherapy or combination of celecoxib and metformin orally for 6 months: celecoxib \[400mg, twice a day\] in arm 1, celecoxib \[400mg, twice a day\] and metformin \[1g, twice a day\] in arm 2.

celecoxib and metformin combination

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \- 1. Patients with familial adenomatous polyposis(FAP) who are 20 to 55 years of age.
• \. FAP patients who have colonic or duodenal polyp. 3. FAP patients who have five or more polyps 2mm or more in diameter in endoscopic examination.

You may not qualify if:

• \. FAP patients who had a history of colectomy within the previous 12 months or need to undergo colectomy within 8 months after randomization.
• \. FAP patients with malignant disease, including colorectal cancer. 3. FAP patients who used NSAIDs (non-steroidal anti-inflammatory drugs) or aspirin three or more times a week within 3 months of randomization.
• \. Pregnant or breast-feeding patients. 5. Patients with cardiovascular diseases, peptic ulcer diseases and diabetes. 6. Patients with abnormal results of serum laboratory tests (renal function and liver function test).

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Department of Internal Medicine, Yonsei University College of Medicine

Seoul, 120-752, South Korea

RECRUITING

MeSH Terms

Conditions

Adenomatous Polyposis Coli

Interventions

Celecoxib

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: August 9, 2024
• Study Start: August 13, 2024
• Primary Completion (Estimated): June 24, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: August 9, 2024

Record last verified: 2024-08

Locations

KR (1)