An Open Label Trial of Duloxetine in the Treatment of Irritable Bowel Syndrome and Comorbid Generalized Anxiety Disorder

The investigators propose to evaluate the effectiveness of duloxetine in treating subjects with both Irritable Bowel Syndrome (IBS) and Generalized Anxiety Disorder (GAD). The investigators hypothesize that duloxetine as a single therapeutic agent will effectively target pain and other core symptoms of IBS as well as GAD in this patient population with both conditions.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome; Generalized Anxiety Disorder
• Intervention / Treatment: Drug: Duloxetine

Detailed Description

Generalized Anxiety Disorder (GAD) is commonly associated with Irritable Bowel Syndrome(IBS). The etiology of IBS remains unknown and it is often refractory to treatment. Duloxetine has demonstrated efficacy in the treatment of GAD as well as other pain disorders including fibromyalgia and diabetic neuropathy.

We plan to study 30 subjects with diagnoses of IBS and GAD between the ages of 18 and 65 years. There will be a single-blind placebo-run-in for the first 2 weeks, followed by open-label duloxetine for 12 weeks flexibly titrated to 120 mg/day. Subjects will be informed that they will receive placebo for 2 weeks during the trial. All study visits will be at Allegheny General Hospital Department of Psychiatry. The study consists of a total of nine office visits.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-65 years of age
• Active IBS diagnosis by a gastroenterologist
• Generalized Anxiety Disorder diagnosed by DSM-IV TR criteria and the Mini International Neuropsychiatric Interview for the DSM-IV (Mini)
• No changes in any non study medication once starting the study

Exclusion Criteria:

• Current diagnoses of Major Depressive Disorder, Panic Disorder, Social Phobia, Post Traumatic Stress Disorder, Obsessive Compulsive Disorders, Eating Disorders, Somatoform Disorders, Drug or alcohol abuse or dependence, or severe personality disorder
• Lifetime history of any Bipolar Disorder or Psychotic Disorder
• Concurrent GI disorders falling outside of Rome III Functional GI disorders
• Pregnant women or sexually active female subjects not using medically acceptable method of contraception
• Current suicidal ideation
• Unstable medical condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Duloxetine; Two weeks of placebo run in followed by 12 weeks of Duloxetine.

Drug: Duloxetine; All subjects will receive single-blind placebo for the first two weeks, and then duloxetine for the next 12 weeks, followed by an up to 2 week taper off of the duloxetine. After 2 weeks of placebo daily, subjects will receive 30 mg per day of duloxetine for two weeks, then titrated up to 60 mg per day of duloxetine at week 2. A dosage decrease to 30 mg daily is permittable after week 2. This will be a flexible dose study with doses of duloxetine progressively increasing at weeks 4 (90 mg daily) and 6 (120 mg daily) in conjunction with CGI-I scores, to reach 120 mg daily or the maximum tolerated dose, if less than 120 mg daily at Week 12. There will be a post-taper follow up appointment at Week 14. Of Note: Amendment IRB Approved 6/14/11 Study Ending at Week 12 with removal of Week 14 visit as part of study.; Other Names: Cymbalta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression Scale	The scale consists of two parts the first part being Severity of Illness and the second part is Global Improvement. We report the Global improvement scale. The Global Improvement is a 1-7 change scale of global improvement since inclusion in the project ranging with 1 "very much improved", 4 "no change", and 7 "very much worse."	endpoint [12 weeks]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Anxiety Rating Scale	The HAM-A is a 14 question scale with five responses. Responses range from 0 "not present" to 4 "very severe." The total score ranges from 0 to 56. Higher values represent a worse outcome.	endpoint [12 weeks]
Irritable Bowel Syndrome-Quality of Life Scale	The IBS-QOL consists of 34 items, each with a five-point response scale. Ratings range from 1 "not at all" to 5 "extremely" or "a great deal" Higher responses on the scale indicate worse outcome. A minimal total score would be 34, maximum 170.	endpoint [12 weeks]
Irritable Bowel Syndrome Severity Scoring System	This is a 4 item Likert scale with each assessment being 100 mm scored from measuring from 0 to 400. Higher numbers indicate worse outcome.	endpoint [12 weeks]

Collaborators and Investigators

• Sponsor: West Penn Allegheny Health System
• Investigators: Principal Investigator: Alicia J Kaplan, MD, West Penn Allegheny Health System

Publications and helpful links

General Publications

• Kaplan A, Franzen MD, Nickell PV, Ransom D, Lebovitz PJ. An open-label trial of duloxetine in patients with irritable bowel syndrome and comorbid generalized anxiety disorder. Int J Psychiatry Clin Pract. 2014 Jan;18(1):11-5. doi: 10.3109/13651501.2013.838632. Epub 2013 Sep 20.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: August 17, 2009
• First Submitted That Met QC Criteria: August 17, 2009
• First Posted (Estimate): August 18, 2009

Study Record Updates

• Last Update Posted (Estimate): July 9, 2014
• Last Update Submitted That Met QC Criteria: June 8, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Irritable Bowel Syndrome; IBS; Generalized Anxiety Disorder; GAD
• Additional Relevant MeSH Terms: Mental Disorders; Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Disease; Irritable Bowel Syndrome; Anxiety Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: RC-4656