Niclosamide for Familial Adenomatous Polyposis

Sponsor

Yonsei University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04296851

Collaborator

(none)

Enrollment

Location

Arms

35.6

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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. Niclosamide, an anti-helminthic drug, has recently been suggested to have a suppressive effect on tumorigenesis via inhibition of Wnt pathway, and have no significant safety issues. The investigators devised a double-blind randomized controlled trial to evaluate the effect of niclosamide on polyps of colorectum and duodenum in FAP patients.

Condition or Disease	Intervention/Treatment	Phase
Familial Adenomatous Polyposis	Drug: Niclosamide Drug: placebo	Phase 2

Detailed Description

This clinical trial is a double-blind randomized controlled trial to evaluate the effect of niclosamide on polyps of colorectum and duodenum in FAP patients. FAP patients, satisfied an enrollment criteria, will be randomly assigned in a 2:1 ratio to receive niclosamide (650 mg) or placebo tablets orally once a day for 6 months. The base-line and six-month endoscopic examination (colonoscopy/sigmoidoscopy and upper gastrointestinal endoscopy) will be recorded, and photographs will be taken at the tattoo-marked area. The number and size of polyps, and a qualitative assessment of the total extent of polyposis will be measured. If there is no significant improvement in any of the 12 initial cases (niclosamide 8: placebo 4), this trial will be discontinued.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

double blind randomized

Primary Purpose:

Treatment

Official Title:

The Chemopreventive Effect of Niclosamide in Patients With Familial Adenomatous Polyposis: Double Blinded Randomized Controlled Study

Actual Study Start Date :

Feb 14, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: niclosamide 650mg daily	Drug: Niclosamide The subjects will be randomly assigned in a 2:1 ratio to receive niclosamide or identical-appearing placebo tablets orally for 6 months: niclosamide 650mg once a day in arm 1, placebo once a day in arm 2.
Placebo Comparator: placebo identical- appearing placebo	Drug: placebo The subjects will be randomly assigned in a 2:1 ratio to receive niclosamide or identical-appearing placebo tablets orally for 6 months: niclosamide 650mg once a day in arm 1, placebo once a day in arm 2.

Arm

Intervention/Treatment

Experimental: niclosamide

650mg daily

Drug: Niclosamide

The subjects will be randomly assigned in a 2:1 ratio to receive niclosamide or identical-appearing placebo tablets orally for 6 months: niclosamide 650mg once a day in arm 1, placebo once a day in arm 2.

Placebo Comparator: placebo

identical- appearing placebo

Drug: placebo

Outcome Measures

Primary Outcome Measures

Mean percentage change of the number and size of polyps in colon and/or duodenum. [After six-month administration of niclosamide/placebo]
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 the subjects with retained rectum after colectomy and ileorectal anastomosis, sigmoidoscopy will be performed. 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.

Secondary Outcome Measures

A qualitative assessment of the total extent of colorectal polyposis [After six-month administration of niclosamide/placebo]
A qualitative assessment of the total extent of colorectal polyposis will be conducted via video review(at base line and month 6) by two endoscopists experienced in the management of FAP, and scored as the same as, better than, or worse than base-line endoscopic findings, without the endoscopists' being aware of treatment group.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with familial adenomatous polyposis(FAP) who are 20 to 65 years of age.
FAP patients who have colonic or duodenal polyp.
FAP patients who have five or more polyps 2mm or more in diameter in endoscopic examination.

Exclusion Criteria:

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.
FAP patients who used NSAIDs (non-steroidal anti-inflammatory drugs) or aspirin three or more times a week within 6 months of randomization.
Pregnant or breast-feeding patients. 6. Patients with abnormal results of serum laboratory tests (renal function and liver function test).