Stricture Definition and Treatment (STRIDENT) Drug Therapy Study

Study Overview
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Brief Summary
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Two thirds of patients with Crohn's disease require intestinal surgery at some time in their life. Intestinal strictures, that is narrowing of the bowel due to inflammation and scarring, are the most common reason for surgery. Despite the high frequency, associated disability, and cost there are no are no treatment strategies that aim to improve the outcome of this disease complication. The STRIDENT (stricture definition and treatment) studies aim to develop such strategies.

Detailed Description
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Prospective randomised controlled study. Patients with Crohn's Disease who have symptomatic inflammatory intestinal strictures will be randomised to receive standard drug therapy (Anti-TNF monotherapy at standard dose) or intensive drug therapy (Intense Anti-TNF dose induction and escalation for continued inflammation in combination with thiopurine) for 12 months.

Official Title
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Stricture Definition and Treatment (STRIDENT) Drug Therapy Study

Conditions
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Crohn Disease, Inflammatory Bowel Diseases, Stricture; Bowel

Intervention / Treatment
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* Drug: Adalimumab Injection
* Drug: Thiopurine
* Procedure: Endoscopic balloon dilatation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inflammatory bowel disease patients with intestinal stricture(s) identified on CT, MRI or endoscopy. Exclusion Criteria: Acute bowel obstruction requiring urgent surgical intervention Deemed by treating physician to have high risk of acute bowel obstruction Concurrent active perianal sepsis Internal fistulising disease in association with strictures (entero-enteric stulas) Low rectal or anal strictures Evidence of dysplasia or malignancy from stricture biopsies or adjacent mucosal biopsies Patients for whom endoscopy is not suitable due to co-morbidities or clinical state Inability to give informed consent Suspected perforation of the gastrointestinal tract Pregnancy Inability to undergo MRI small bowel due to a contraindication.

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard drug therapy<br>Adalimumab monotherapy, Standard Dose induction (160mg at week 0, 80mg week 2 and 40mg fortnightly thereafter) | Drug: Adalimumab Injection<br>* Standard dose adalimumab induction and maintenance<br>Procedure: Endoscopic balloon dilatation<br>* Prior to randomization, suitable patients may undergo endoscopic balloon dilatation. Patients undergoing dilatation will be stratified to ensure equal numbers in each study arm.<br>|
| Experimental: Intensive drug therapy<br>Adalimumab in combination with dose optimized thiopurine, Intensive induction (160mg weekly for 4 weeks then 40mg fortnightly). Anti-TNF dose may be increased if ongoing inflammation every 4 months until study endpoint. | Drug: Adalimumab Injection<br>* Standard dose adalimumab induction and maintenance<br>Drug: Thiopurine<br>* Dose optimized thiopurine<br>Procedure: Endoscopic balloon dilatation<br>* Prior to randomization, suitable patients may undergo endoscopic balloon dilatation. Patients undergoing dilatation will be stratified to ensure equal numbers in each study arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in obstructive symptoms. | Improved pain and or frequency of pain compared to baseline. Obstructive symptoms determined by prospective diary documenting number of episodes of pain in previous 2 weeks and severity of the pain episodes using four-level Likert scale. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in symptoms | Improved pain and or frequency of pain compared to baseline. Obstructive symptoms determined by prospective diary documenting number of episodes of pain in previous 2 weeks and severity of the pain episodes using four-level Likert scale. | 4, 8 and 12 months | 
| Improvement in biochemical inflammatory parameters | Serum CRP and fecal calprotectin | 12 months | 
| Improvement in imaging parameters (Intestinal ultrasound) | Limberg's score | 12 months | 
| Improvement in imaging parameters | Modified MaRIA score | 12 months | 
| Surgery | The number of patients that require surgical resection of stricture due to failure of drug therapy. | 12 months | 
| Improvement in patient reported outcomes (PROs) | SF36 | 12 months | 
| Improvement in patient reported outcomes (PROs) | IBDQ | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn Disease, Inflammatory Bowel Disease, Intestinal stricture