Clinical trial NCT00477165: Citalopram in Irritable Bowel Syndrome
Official title: Effect of Citalopram on Clinical Symptoms and Visceral Sensitivity in Patients With Irritable Bowel Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome
Keywords: Irritable bowel syndrome
Antidepressant
IBS
Serotonin-reuptake inhibitor
SSRI
Visceral sensitivity
Barostat
Quality of life
Depression
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2007-05-22
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hypotheses:

1. 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.
2. Secondary null hypotheses:

   1. 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.
   2. 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.

Eligibility criteria: Inclusion Criteria:

Inclusion criteria are:

1. Fulfilling Rome II IBS definition;
2. Age ≥18 yrs and able to give informed consent;
3. 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:

1. Current psychiatric diagnosis or active treatment with antidepressants;
2. Pregnancy;
3. Major systemic illness, or illness that could explain IBS-like symptoms;
4. Active IBS therapy other than fiber or loperamide.

Primary outcomes:
measure: Count of Participants Who Self-reported "Adequate Relief"
timeFrame: Baseline, weekly for 8 weeks
Secondary outcomes:
measure: Change From Baseline in IBS-QOL Score at Week 8
timeFrame: Baseline; Week 8
measure: Mean Sensation Score as a Function of Distending Pressure at the End of the Study
timeFrame: Week 8
measure: Urgency Score as a Function of Distending Pressure at the End of the Study
timeFrame: Week 8
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF
state: California
Study officials:
affiliation: University of California, San Francisco
name: Uri Ladabaum, M.D., M.S.
role: PRINCIPAL_INVESTIGATOR
References: