Effects of Mesalamine and Amitriptyline on Irritable Bowel Syndrome

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effects of Mesalamine and Amitriptyline drugs on the Quality of Life and Symptom Severity Scale in patients with Diarrhea- Predominant Irritable Bowel Syndrome (IBS-D). All patients will fill three validated questionnaires (IBS Symptom Severity Scale (IBS-SSS) , Hospital Anxiety and Depression Scale (HADS ) and IBS Quality of Life (IBS-QOL) ) at the beginning of trial and at weeks 2,4,6 and 8 of treatment. Serum Immune Bio markers will be measured at 0,4, and 8 weeks of treatment. This study is a clinical trial upon 90 patients with Diarrhea- Predominant IBS (IBS-D) who are referred for the first time to our private gastrointestinal clinic from 2014 until 2016. All patients who meet the inclusion criteria enrolled for a 2-week period screening phase. In order to exclude patients with Lactose intolerance, all patients take a lactose-free diet for 14 days before inclusion and patients whose symptoms improve by this regimen will be excluded. This trial is a double-blind study and all patients will be assigned randomly to three groups: Mesalazine group: Patients receive Asacol (800 mg/TDS) and a placebo agent similar to Amitriptyline (10 mg/HS) for 8 weeks Amitriptyline group: Patients receive Amitriptyline (10 mg/HS) and a placebo like Asacol (800 mg/ TDS) for 8 weeks Control group (placebo group): Patients receive placebo like Asacol (800 mg/TDS) and placebo similar to Amitriptyline (10 mg/HS) for 8 weeks Ethical considerations: All patients will fulfill an informed consent Drugs are available without any charge Observation of Helsinki ethical statement

Official Title
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Therapeutic Effects of Mesalamine and Amitriptyline in IBS: a Randomized Clinical Trial

Conditions
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Diarrhea- Predominant Irritable Bowel Syndrome, Quality of Life

Intervention / Treatment
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* Drug: Mesalazine(asacol 800 mg)
* Drug: Amitriptyline
* Drug: placebo like asacol
* Drug: placebo like amitriptyline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Establishment of diagnosis of IBS by ROME-III criteria Age > 18 years old and < 65 years old Normal colonoscopy or sigmoidoscopy Negative celiac serologic markers Normal complete blood count (CBC) and stool exam and stool culture The patient should not be administered Anti-inflammatory drugs such as Nonsteroidal Antiinflammatory Drugs(NSAIDs), oral or parenteral Antibiotics, Corticosteroids, Mast cell stabilizers, Narcotics, Antidepressants and Immunosuppressive Agents. Normal thyroid-stimulating hormone (TSH ) Normal Serum Calcium Educated patient Exclusion Criteria: Breast feeding and Pregnancy Presence of acute or chronic inflammation which can change the basal level of cytokines Allergic disorders like Asthma (family and personal history) Presence of organic disease like Diabetes mellitus or Psychiatric disorders. Alcohol dependency and addiction to Tobacco and Opium Patients who do not use efficient contraception method History of extensive abdominopelvic surgery except Appendectomy, Cholecystectomy, Hysterectomy and Cesarian-Section Presence of Celiac disease History of Crohn's disease, Ulcerative Colitis and Diverticulitis during the previous year. History of Cardiac, Pulmonary, Hepatic and Renal disease Presence of chronic GI disorders History of Allergy to Aspirin, Mesalamine or Sulpha compounds History of Lymphocytic or Microscopic Colitis History of significant weight loss ( 10% of body weight during 6 months), nocturnal sweating, GI bleeding and family history of Colon cancer Patients with Lactose intolerance disease Presence of Bowel Acid Malabsorption

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesalazine(asacol 800 mg)<br>patients receive asacol (800 mg/TDS) and a placebo agent similar to amitriptyline (10 mg/HS) for 8 weeks | Drug: Mesalazine(asacol 800 mg)<br> <br> Drug: placebo like amitriptyline<br> <br> |
| Experimental: Amitriptyline<br>patients receive amitriptyline (10 mg/HS) and a placebo like asacol (800 mg/ TDS) for 8 weeks | Drug: Amitriptyline<br> <br> Drug: placebo like asacol<br> <br> |
| Placebo Comparator: placebo group<br>patients receive placebo like asacol (800 mg/TDS) and placebo similar to amitriptyline (10 mg/HS) for 8 weeks | Drug: placebo like asacol<br> <br> Drug: placebo like amitriptyline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life | All patients will fill three validated questionnaires (IBS-SSS , HADS and IBS-QOL ) at the beginning of trial and at weeks 2,4,6 and 8 of treatment to assess quality of life and symptom severity scale in patients with diarrhea- predominant . | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum immune biomarkers | Serum immune biomarkers will be measured at 0,4, and 8 weeks of treatment. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mesalamine, amitriptyline, Severity of Illness Index