Citalopram in Irritable Bowel Syndrome

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00477165
• Collaborator: (none)
• Enrollment: 54
• Location: 1
• Arms: 2
• Duration (Months): 98
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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:

3. 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.

4. 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.

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome	Drug: Citalopram; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Citalopram on Clinical Symptoms and Visceral Sensitivity in Patients With Irritable Bowel Syndrome
• Study Start Date: Apr 1, 2001
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Citalopram One 20mg capsule per day for 4 weeks, then 2 capsules per day (40mg) for 4 weeks	Drug: Citalopram; 20mg/day for 4 weeks, then 40 mg/day for 4 weeks; Other Names: Celexa Cipramil
Placebo Comparator: Placebo Identical to citalopram 20mg capsule. One capsule per day for 4 weeks, then 2 capsules per day for 4 weeks	Drug: Placebo; Identical to citalopram 20mg capsules; 1 capsule/day for 4 weeks, then 2 capsules/day for 4 weeks

Outcome Measures

Primary Outcome Measures

1. Count of Participants Who Self-reported "Adequate Relief" [Baseline, weekly for 8 weeks]

   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.

Secondary Outcome Measures

1. Change From Baseline in IBS-QOL Score at Week 8 [Baseline; 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.

2. Mean Sensation Score as a Function of Distending Pressure at the End of the Study [Week 8]

   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.

3. Urgency Score as a Function of Distending Pressure at the End of the Study [Week 8]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF	San Francisco	California	United States	94143

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Uri Ladabaum, M.D., M.S., University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Uri Ladabaum, Principle Investigator, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00477165
• Other Study ID Numbers: H10539-18502
• First Posted: May 22, 2007
• Last Update Posted: Apr 17, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Uri Ladabaum, Principle Investigator, University of California, San Francisco: Irritable bowel syndrome; Antidepressant; IBS; Serotonin-reuptake inhibitor; SSRI; Visceral sensitivity; Barostat; Quality of life; Depression
• Additional relevant MeSH terms: Irritable Bowel Syndrome; Syndrome; Citalopram

Study Results

Participant Flow

Pre-assignment Detail	A total of 234 potentially eligible subjects were identified. Of these, 180 were excluded and 54 enrolled in the study, with 27 each randomized to citalopram and placebo.

Arm/Group Title	Cialopram	Placebo
Arm/Group Description	One 20mg capsule per day for 4 weeks, then 2 capsules per day (40mg) for 4 weeks	Identical to citalopram 20mg capsule. One capsule per day for 4 weeks, then 2 capsules per day for 4 weeks
Period Title: Overall Study
STARTED	27	27
COMPLETED	20	25
NOT COMPLETED	7	2

Baseline Characteristics

Arm/Group Title	Cialopram	Placebo	Total
Arm/Group Description	One 20mg capsule per day for 4 weeks, then 2 capsules per day (40mg) for 4 weeks	Identical to citalopram 20mg capsule. One capsule per day for 4 weeks, then 2 capsules per day for 4 weeks	Total of all reporting groups
Overall Participants	27	27	54
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53	51	52
Sex: Female, Male (Count of Participants)
Female	21 77.8%	23 85.2%	44 81.5%
Male	6 22.2%	4 14.8%	10 18.5%
Region of Enrollment (participants) [Number]
United States	27 100%	27 100%	54 100%

Outcome Measures

1. Primary Outcome

Title	Count of Participants Who Self-reported "Adequate Relief"
Description	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.
Time Frame	Baseline, weekly for 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Citalopram	Placebo
Arm/Group Description	One 20mg capsule per day for 4 weeks, then 2 capsules per day (40mg) for 4 weeks	Identical to citalopram 20mg capsule. One capsule per day for 4 weeks, then 2 capsules per day for 4 weeks
Measure Participants	27	27
Count of Participants [Participants]	12 44.4%	15 55.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Citalopram, Placebo
	Comments	Null hypothesis: number of patients achieving adequate relief is the same in both Citalopram and Placebo groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments	p<0.05 for statistical significance
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.687 to 1.196
	Parameter Dispersion	Type: Value:
	Estimation Comments	Repeated-measures logistic regression model, assuming the citalopram effect builds linearly over time starting at week 3.

2. Secondary Outcome

Title	Change From Baseline in IBS-QOL Score at Week 8
Description	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.
Time Frame	Baseline; Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Citalopram	Placebo
Arm/Group Description	One 20mg capsule per day for 4 weeks, then 2 capsules per day (40mg) for 4 weeks	Identical to citalopram 20mg capsule. One capsule per day for 4 weeks, then 2 capsules per day for 4 weeks
Measure Participants	27	27
Mean (95% Confidence Interval) [units on a scale]	6.3	7.6

3. Secondary Outcome

Title	Mean Sensation Score as a Function of Distending Pressure at the End of the Study
Description	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.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Citalopram	Placebo
Arm/Group Description	One 20mg capsule per day for 4 weeks, then 2 capsules per day (40mg) for 4 weeks	Identical to citalopram 20mg capsule. One capsule per day for 4 weeks, then 2 capsules per day for 4 weeks
Measure Participants	20	25
Distending pressure 12mmHg	1	2
Distending pressure 24mmHg	4	6
Distending pressure 36mmHg	5	7
Distending pressure 48mmHg	7	6

4. Secondary Outcome

Title	Urgency Score as a Function of Distending Pressure at the End of the Study
Description	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.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Citalopram	Placebo
Arm/Group Description	One 20mg capsule per day for 4 weeks, then 2 capsules per day (40mg) for 4 weeks	Identical to citalopram 20mg capsule. One capsule per day for 4 weeks, then 2 capsules per day for 4 weeks
Measure Participants	20	25
Distending pressure 12mmHg	1	2
Distending pressure 24mmHg	4	5
Distending pressure 36mmHg	4	5
Distending pressure 48mmHg	5	5

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	During the study, subjects were asked to call a research coordinator weekly to report completion of questionnaires. If the telephone call was not received, a research coordinator contacted the subject. Subjects were asked to call if they experienced side effects.
Arm/Group Title	Citalopram		Placebo
Arm/Group Description	One 20mg capsule per day for 4 weeks, then 2 capsules per day (40mg) for 4 weeks		Identical to citalopram 20mg capsule. One capsule per day for 4 weeks, then 2 capsules per day for 4 weeks
All Cause Mortality
	Citalopram		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Citalopram		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Citalopram		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/27 (25.9%)		2/27 (7.4%)
Gastrointestinal disorders
Diarrhea	1/27 (3.7%)	1	0/27 (0%)	0
Abdominal pain	1/27 (3.7%)	1	0/27 (0%)	0
General disorders
Fatigue	3/27 (11.1%)	3	0/27 (0%)	0
Insomnia	1/27 (3.7%)	2	0/27 (0%)	0
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/27 (0%)	0	1/27 (3.7%)	1
Psychiatric disorders
Somnolence	0/27 (0%)	0	1/27 (3.7%)	1
Reproductive system and breast disorders
Sexual dysfunction	1/27 (3.7%)	1	0/27 (0%)	0

Limitations/Caveats

Results have been entered as available in the published manuscript; the PI is no longer at UCSF. This trial has the limitation of relatively small sample size. A potential limitation is that patients could have been unblinded based on side effects.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.