To Evaluate the Efficacy and Safety of Rapamycin for Crohn's Disease-related Stricture

Sponsor

The Second Hospital of Nanjing Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT02675153

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Crohn's disease （CD） with stenosis has limited therapeutic options and with high surgical rate. The present clinical trial aims to evaluate the efficacy and safety of rapamycin in the treatment of stricturing Crohn's Disease.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Diseases	Drug: Rapamycin	N/A

Detailed Description

Management of Crohn's disease （CD） with stenosis is challenging and often requires endoscopic dilatation or surgical resection of the strictured bowel. Sirolimus (rapamycin), a macrocyclic antibiotic with immunosuppressive and antineoplastic properties, has been reported as promising rescue therapy for refractory CD. This study aims to evaluate the use of sirolimus for stricturing Crohn's Disease. Patients in this study will receive a continuous dosing schedule of oral sirolimus 2mg daily for six months. Clinical responses were defined as the ability to tolerate the regular diet with vegetable fiber combined with a reduction of ≥ 75% in overall target score and a score of less than two points for each item.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Rapamycin in the Treatment of Crohn's Disease-related Stricture

Actual Study Start Date :

Apr 1, 2015

Anticipated Primary Completion Date :

Oct 1, 2020

Anticipated Study Completion Date :

Oct 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Upper gastrointestinal strictures Patients with upper gastrointestinal strictures were treated with rapamycin (2mg/day, Sirolimus, Roche) for at least six months.	Drug: Rapamycin Participants with gastrointestinal strictures were treated with rapamycin 2mg daily at least six months. Other Names: Sirolimus
Experimental: Lower gastrointestinal strictures Patients with lower gastrointestinal strictures were treated with rapamycin (2mg/day, Sirolimus, Roche) for at least six months.	Drug: Rapamycin Participants with gastrointestinal strictures were treated with rapamycin 2mg daily at least six months. Other Names: Sirolimus

Arm

Intervention/Treatment

Experimental: Upper gastrointestinal strictures

Patients with upper gastrointestinal strictures were treated with rapamycin (2mg/day, Sirolimus, Roche) for at least six months.

Drug: Rapamycin

Participants with gastrointestinal strictures were treated with rapamycin 2mg daily at least six months.

Other Names:

Sirolimus

Experimental: Lower gastrointestinal strictures

Patients with lower gastrointestinal strictures were treated with rapamycin (2mg/day, Sirolimus, Roche) for at least six months.

Drug: Rapamycin

Participants with gastrointestinal strictures were treated with rapamycin 2mg daily at least six months.

Other Names:

Sirolimus

Outcome Measures

Primary Outcome Measures

Response rate [up to 24 weeks]
Response was defined as the following criteria: (a) the ability to tolerate a normal diet (vegetable fiber), with a reduction of ≥ 75% in overall baseline target score and sub-score ≤ 2 (Table S1); (b) no need for ED or surgery; (c) no severe adverse events or any other reasons leading to rapamycin withdrawal.

Secondary Outcome Measures

Adverse events [through study completion, an average of 3 years]
New onset of symptoms and the exacerbation of previous symptoms were recorded as adverse events (AEs)
The rate of surgery or ED after rapamycin [through study completion, an average of 3 years]
For long-term treatment outcomes, the primary endpoint was the rate of surgery or ED after rapamycin.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Chinese patients (≥18 years of age) with a documented definite diagnosis of CD;
the presence of a clinically symptomatic stricture;
strictures confirmed by endoscopy (passage of the endoscope with resistance or not traversable) or imaging (CT enterography (CTE) or MR enterography (MRE).

Exclusion Criteria:

Patients who were pregnant, diagnosed with intestinal perforation, complete intestinal obstruction, any signs of dysplasia or malignancy, or use of anti-tumor necrosis factor (TNF) in the last three months;
Patients who were not followed up between the inception of medication and any other subsequent treatments.