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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Crohn's Diseases

Intervention / Treatment
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* Drug: Rapamycin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upper gastrointestinal strictures<br>Patients with upper gastrointestinal strictures were treated with rapamycin (2mg/day, Sirolimus, Roche) for at least six months. | Drug: Rapamycin<br>* Participants with gastrointestinal strictures were treated with rapamycin 2mg daily at least six months.<br>* Other names: Sirolimus;|
| Experimental: Lower gastrointestinal strictures<br>Patients with lower gastrointestinal strictures were treated with rapamycin (2mg/day, Sirolimus, Roche) for at least six months. | Drug: Rapamycin<br>* Participants with gastrointestinal strictures were treated with rapamycin 2mg daily at least six months.<br>* Other names: Sirolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | 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. | up to 24 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rapamycin, stricture, fibrosis