Citalopram in Irritable Bowel Syndrome

Study Overview
=================
Brief Summary
-----------------
Hypotheses: Primary null hypothesis: The rate of clinical response, assessed as patient-reported global symptom rating and adequate relief of IBS symptoms, does not differ between non-depressed IBS patients treated with the SSRI citalopram and patients treated with placebo. Secondary null hypotheses: Changes in disease-related quality of life, assessed with the IBS-QOL instrument, do not differ between patients treated with the SSRI citalopram and patients treated with placebo. Changes in rectosigmoid visceral sensitivity, assessed by barostat balloon distention, do not differ between patients treated with the SSRI citalopram and patients treated with placebo.

Detailed Description
-----------------
Irritable bowel syndrome (IBS) affects an estimated 15 million Americans at a cost of $1.7 billion per year. Visceral hypersensitivity is present in many patients with IBS, but its contribution to clinical symptoms is unclear. Tricyclic antidepressants may be beneficial in IBS, but their side effects can be unacceptable. Because they are better tolerated, selective serotonin reuptake inhibitors (SSRIs) are often used to treat IBS, but their efficacy in IBS has not been examined in controlled studies. We propose a randomized, placebo-controlled trial of SSRI treatment in IBS. Non-depressed patients will be studied in order to assess SSRI effects on IBS independent of depression. Our specific aims are: 1) To determine whether the SSRI citalopram is superior to placebo in improving clinical symptoms, disease-related quality of life, and tolerance to rectal balloon distension; 2) To assess whether symptomatic improvement is correlated with improvement in quality of life and/or visceral sensitivity. Subjects will fulfill Rome II IBS criteria, will have normal screening studies, and will not be depressed or on antidepressants. Global and specific symptoms, and satisfaction will be rated daily during a 1-week baseline. Subjects will then be randomized in concealed, double-blind fashion to citalopram or placebo, will complete the validated IBS-QOL instrument, and will undergo rectal compliance and sensory testing with a barostat. Subjects will be treated and will rate symptoms and satisfaction weekly for a total of 8 weeks, and also daily during the final week for comparison with the baseline. At study end, subjects will again complete the IBS-QOL and undergo a barostat study. For the primary outcome, we estimate that to detect a standardized effect size of 0.9 in global symptom rating with 2-sided α=0.05 and β=0.1, 54 subjects are needed. We plan to enroll 60 subjects, which will allow detection of an odds ratio for response (adequate relief) of 4.5 with 2-sided α=0.05 and β=0.2. If the odds ratio for this dichotomous outcome is smaller, this study will provide pilot data for a larger trial. Clinical symptoms are expected to fluctuate. Even if citalopram is not superior to placebo, prospectively collected data will illuminate the relationship between symptoms and visceral sensitivity, and the placebo effect.

Official Title
-----------------
Effect of Citalopram on Clinical Symptoms and Visceral Sensitivity in Patients With Irritable Bowel Syndrome

Conditions
-----------------
Irritable Bowel Syndrome

Intervention / Treatment
-----------------
* Drug: Citalopram
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion criteria are: Fulfilling Rome II IBS definition; Age ≥18 yrs and able to give informed consent; Normal sigmoidoscopy, colonoscopy or barium enema within 5 years, normal complete blood count and thyroid studies, and negative stool ova and parasite exam for patients with diarrhea. Exclusion Criteria: Exclusion criteria are: Current psychiatric diagnosis or active treatment with antidepressants; Pregnancy; Major systemic illness, or illness that could explain IBS-like symptoms; Active IBS therapy other than fiber or loperamide.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Citalopram<br>One 20mg capsule per day for 4 weeks, then 2 capsules per day (40mg) for 4 weeks | Drug: Citalopram<br>* 20mg/day for 4 weeks, then 40 mg/day for 4 weeks<br>* Other names: Cipramil;|
| Placebo Comparator: Placebo<br>Identical to citalopram 20mg capsule. One capsule per day for 4 weeks, then 2 capsules per day for 4 weeks | Drug: Placebo<br>* Identical to citalopram 20mg capsules; 1 capsule/day for 4 weeks, then 2 capsules/day for 4 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants Who Self-reported Adequate Relief | Participants were asked weekly to answer subjectively whether weekly adequate relief from IBS symptoms was achieved. Overall response was defined as having achieved adequate relief in at least 3 of the past 6 weeks. | Baseline, weekly for 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in IBS-QOL Score at Week 8 | The IBS-QOL is a self-report quality-of-life measure specific to Irritable Bowel Syndrome (IBS) that can be used to assess the impact of IBS and its treatment. The IBS-QOL consists of 34 statements about bowel problems, each with a five-point response scale ranging from 1 (no problems) to 5 (most problems). The individual scores are summed and averaged for a total score, then transformed to a 0-100 scale for ease of interpretation with higher scores indicating better IBS-specific quality of life. | Baseline; Week 8 | 
| Mean Sensation Score as a Function of Distending Pressure at the End of the Study | A 500mL polyethylene bag was passed into the rectum, with tubing connected to a barostat, which was controlled by a computer that recorded bag pressure, volume, and corrected volume every second. After 5 minutes, the bag was unfurled with 100mL of air and deflated; with inflations lasting 45 seconds from 0 up to 60 mmHg, increasing by 3 mmHg, and separated by 45-second deflations, subjects rated sensation 30 seconds into each inflation. Sensation score scale: 0=no inflation sensation, 1-5=increasing painless sensation, 6=threshold pain, 10=worst imaginable pain. | Week 8 | 
| Urgency Score as a Function of Distending Pressure at the End of the Study | A 500mL polyethylene bag was passed into the rectum, with tubing connected to a barostat, which was controlled by a computer that recorded bag pressure, volume, and corrected volume every second. After 5 minutes, the bag was unfurled with 100mL of air and deflated; with inflations lasting 45 seconds from 0 up to 60 mmHg, increasing by 3 mmHg, and separated by 45-second deflations, subjects rated urgency for bowel movement 30 seconds into each inflation. Urgency score scale: 0=no urgency, 1=threshold urgency, 5=worst imaginable urgency. | Week 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Irritable bowel syndrome, Antidepressant, IBS, Serotonin-reuptake inhibitor, SSRI, Visceral sensitivity, Barostat, Quality of life, Depression