Effects of Mesalamine and Amitriptyline on Irritable Bowel Syndrome

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

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:

1. Mesalazine group: Patients receive Asacol (800 mg/TDS) and a placebo agent similar to Amitriptyline (10 mg/HS) for 8 weeks
2. Amitriptyline group: Patients receive Amitriptyline (10 mg/HS) and a placebo like Asacol (800 mg/ TDS) for 8 weeks
3. 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:

1. All patients will fulfill an informed consent
2. Drugs are available without any charge
3. Observation of Helsinki ethical statement

Study Overview

• Status: Withdrawn
• Conditions: Quality of Life; Diarrhea- Predominant Irritable Bowel Syndrome
• Intervention / Treatment: Drug: Amitriptyline; Drug: Mesalazine(asacol 800 mg); Drug: placebo like amitriptyline; Drug: placebo like asacol

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Gastrointestinal Private Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Establishment of diagnosis of IBS by ROME-III criteria
2. Age > 18 years old and < 65 years old
3. Normal colonoscopy or sigmoidoscopy
4. Negative celiac serologic markers
5. Normal complete blood count (CBC) and stool exam and stool culture
6. 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.
7. Normal thyroid-stimulating hormone (TSH )
8. Normal Serum Calcium
9. Educated patient

Exclusion Criteria:

1. Breast feeding and Pregnancy
2. Presence of acute or chronic inflammation which can change the basal level of cytokines
3. Allergic disorders like Asthma (family and personal history)
4. Presence of organic disease like Diabetes mellitus or Psychiatric disorders.
5. Alcohol dependency and addiction to Tobacco and Opium
6. Patients who do not use efficient contraception method
7. History of extensive abdominopelvic surgery except Appendectomy, Cholecystectomy, Hysterectomy and Cesarian-Section
8. Presence of Celiac disease
9. History of Crohn's disease, Ulcerative Colitis and Diverticulitis during the previous year.
10. History of Cardiac, Pulmonary, Hepatic and Renal disease
11. Presence of chronic GI disorders
12. History of Allergy to Aspirin, Mesalamine or Sulpha compounds
13. History of Lymphocytic or Microscopic Colitis
14. History of significant weight loss ( 10% of body weight during 6 months), nocturnal sweating, GI bleeding and family history of Colon cancer
15. Patients with Lactose intolerance disease
16. Presence of Bowel Acid Malabsorption

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Collaborators: Tillotts Pharma AG
• Investigators: Study Director: Nasser Ebrahimi Daryani, Professor, tehran university of medical science; Principal Investigator: Zahra Azizi, Researcher, Iran University of Medical Sciences; Study Director: Mohammad Bashashati, Research Associate, University of Calgary; Study Director: Nima Rezaei, Assistant Professor, tehran university of medical science

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: March 27, 2014
• First Submitted That Met QC Criteria: July 11, 2014
• First Posted (Estimate): July 15, 2014

Study Record Updates

• Last Update Posted (Estimate): April 15, 2016
• Last Update Submitted That Met QC Criteria: April 14, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: mesalamine; Severity of Illness Index; amitriptyline
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Amitriptyline; Mesalamine
• Other Study ID Numbers: 8811215278