Role of Roflumilast in Ulcerative Colitis

Study Overview
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Brief Summary
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This study aims to investigate possible efficacy and safety of Roflumilast in adult patients with ulcerative colitis disease .

Detailed Description
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Study design and study population This study will be randomized, controlled, parallel study. It will be conducted on 52 patient having with mild to moderate degree ulcerative colitis disease divided into two groups Group 1 (n=26): Patients will receive conventional treatment only (corticosteroids +immune suppressive +amino salicylic acid) for 3 months. Group 2 (n=26): Patients will receive previous conventional treatment and Roflumilast (500 mcg ) orally once daily for 3 months Patient will be selected from Gastroenterology and Endoscopy Unit, Internal Medicine Department, Tanta University Hospital. A written informed consent will be obtained from all patients This study will be approved by the Research Ethics Committee of Tanta University. Any unexpected risks appeared during the course of research will be reported to the participants and ethical committee on time and documented through an adverse effects reporting form . Randomization will be carried out based on days of hospital admission

Official Title
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Clinical Study to Evaluate the Possible Efficacy and Safety of Roflumilast in Patients With Ulcerative Colitis.

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Roflumilast 500 Ug ORAL TABLET [Daliresp]
* Drug: corticosteroids +immune suppressive +amino salicylic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients referred to endoscopy units in Tanta University hospitals during the period of the study. Patient with mild to moderate UC diagnosed as: Clinical signs: Patients with moderate clinical disease have frequent loose, bloody stools (>4per day), mild anemia, and abdominal pain that is not severe. Patients have minimal signs of systemic toxicity, including a low-grade fever. Adequate nutrition is usually maintained, and weight loss. Endoscopy : are necessary to establish the chronicity of inflammation and to exclude other causes of colitis. Exclusion Criteria: Other inflammatory bowel disease (crohn's disease) . Patients <15 and >80 years Patients who didn't give consent to participate in the study Patients with contraindications of colonoscopy e.g. suspected colonic perforation, acute peritonitis, pregnancy, severe bleeding tendency, shock, uncooperative patient and if toxic mega colon is suspected were excluded History of allergic reaction to Roflumilast or any component of the formulation Like rash , hives ,itching and redness . Depression , thoughts of suicide , anxiety and emotional instability . Excessive weight loss . Moderate to severe hepatic impairment (child pugh class B or C) . Strong (CYP3A4) inducers : Barbiturates (phenobarbital) , Carbamazepine , Phenytoin , Rifampicin ( Risk , X interaction ) Loxapine ( Risk , X interaction )

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: It will be conducted on 52 patient having with mild to moderate degree ulcerative colitis disease divided into two groups Group 1 (n=26): Patients will receive conventional treatment only (corticosteroids +immune suppressive +amino salicylic acid) for 3 months. Group 2 (n=26): Patients will receive previous conventional treatment and Roflumilast (500 mcg ) orally once daily for 3 months
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: conventional treatment group<br>Group 1 (n=26): Patients will receive conventional treatment only of ulcerative colitis for 3 months. | Drug: corticosteroids +immune suppressive +amino salicylic acid<br>* conventional treatment<br>|
| Experimental: experimental treatment group<br>Patients will receive previous conventional treatment and Roflumilast (500 mcg ) orally once daily for 3 months | Drug: Roflumilast 500 Ug ORAL TABLET [Daliresp]<br>* Roflumilast has been approved by U.S. Food and Drug Administration (FDA) for attenuating bronchial and dermatological disorders<br>* Other names: andomilast;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical improvement in ulcerative colitis severity | To demonstrate the efficacy of Roflumilast and clinical improvement in (Mayo disease activity index) for assessment of ulcerative colitis severity | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in serum levels of the measured biochemical parameters | demonstrate changes in serum levels of the measured biochemical parameters Tumor necrosis factor-alpha (TNF-α) as pro inflammatory marker (ELISA). Signal transducer and activator of transcription 3 (STAT3) as a potential marker for apoptosis ( ELISA) Caspase-3 as a potential marker for apoptosis (ELISA). | 7 months |