A Placebo-Controlled Trial of Pregabalin (Lyrica) for Irritable Bowel Syndrome

Study Overview
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Brief Summary
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This study is being done to see if Lyrica helps people with irritable bowel syndrome.

Detailed Description
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Lyrica is the trade name for pregabalin, which was first approved by the FDA in June 2005 and has been available through prescription since fall 2005, and is marketed by Pfizer. Lyrica is known to have clinical efficacy treating pain disorders including irritable bowel syndrome-related conditions such as fibromyalgia.

Official Title
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A Placebo-Controlled Trial of Pregabalin (Lyrica) for Irritable Bowel Syndrome

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of Irritable Bowel Syndrome (IBS) Experience pain with relief with defecation 50/100 or greater of pain or discomfort scores during the two-week baseline period At least three pain attacks in a month, with at least three episodes of pain intensity equal to or exceeding 50/100 U.S. resident English-speaking (able to provide consent and complete questionnaires) Able to participate in all aspects of the study Exclusion Criteria: Known alternative/concurrent gastrointestinal diagnosis (e.g. Crohn's disease, ulcerative colitis, microscopic colitis, active celiac sprue, chronic pancreatitis or pancreatic insufficiency, scleroderma, chronic intestinal pseudo-obstruction, bacterial overgrowth, recent (<6 months) intestinal bacterial/protozoal/ parasitic infections, HIV, active pelvic floor dysfunction, paraplegia or quadriplegia); Current symptoms of severe depression, as measured by Hospital Anxiety and Depression Scale (HADS) score (greater or less than 15); Mental retardation or any condition requiring a legal guardian; Current or past history of psychotic disorder (schizophrenia, bipolar disorder) Recent or current use (within past 30 days) of drugs that interact with Pregabalin: Rosiglitazone (Avandia) or Pioglitazone (Actos) Narcotic anti-pain medications (e.g. oxycodone, morphine) Anti-anxiety medications (e.g. lorazepam, alprazolam, diazepam) Unable to withdraw medications at least 72 hours prior to the study, because we will evaluate patient's response to pregabalin therapy for relief of IBS-associated pain and disturbed sleep. Non-narcotic anti-pain medications (e.g. nonsteroidal antiinflammatory drug (NSAIDs), ultram, neurontin, etc.) Mexiletine, steroids, dextromethorphan. Insomnia medications (e.g. benzodiazepines, zolpidem, diphenhydramine, melatonin, etc.) Planned surgery (especially transplant) or anesthesia exposure during trial Are pregnant, lactating, likely to become pregnant during medication phase and not willing to use a reliable form of contraception (barrier contraceptives, diaphragm, injections, intrauterine device, surgical sterilization, or abstinence) Recent or current use (within 30 days) of Pregabalin Known allergy to Pregabalin Significant acute or chronic progressive neurologic, hepatic, renal, cardiovascular, respiratory or metabolic disease Recent history of alcohol or substance dependence use or abuse Another household member or relative participating in the study Professional drivers or operators of heavy machinery Major cardiovascular events in the last 6 months Use of IBS-specific drugs such as tegaserod (Zelnorm) and Lotronex (Alosetron) (within 30 days) Participation in another clinical trial (within 30 days)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pregabalin<br>Subjects randomized to this arm will receive the following dosage: 75 mg (one tablet) twice a day for three days, increasing to 150 mg (2 tablets) twice a day for three days, escalating to 225 mg (three tablets) twice a day, through week 12, day 1. Days 2-4 of week 12, participants will begin tapering and will receive 150 mg (two tablets) two times a day and then days 5-7, participants will receive 75 mg two times a day for the duration of the study. | Drug: Pregabalin<br>* Dose: 75 mg twice a day for three days, increasing to 150 mg (2 tablets) twice a day for three days, escalating to 225 mg (three tablets) twice a day, through week 12, day 1. Days 2-4 of week 12, participants will begin tapering and will receive 150 mg (two tablets) two times a day and then days 5-7, participants will receive 75 mg two times a day for the duration of the study.<br>* Other names: Lyrica;|
| Placebo Comparator: Placebo<br>Subjects randomized to this arm will receive placebo matching the study drug. | Drug: Placebo<br>* A matching placebo will be administered twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Pain Bowel Symptom Scale (BSS) Score Over Last 4 Weeks of Study (Weeks 9-12) | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | weeks 9-12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Overall Severity of Irritable Bowel Syndrome (IBS) Symptoms BSS Score Last 4 Weeks of the Study (Weeks 9-12) | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | weeks 9-12 | 
| Mean Constipation BSS Score Over Last 4 Weeks of Study (Weeks 9-12) | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | Weeks 9-12 | 
| Mean Diarrhea BSS Score Over the Last 4 Weeks of the Study (Weeks 9-12) | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | Weeks 9-12 | 
| Mean Bloating BSS Score Over the Last 4 Weeks of the Study (Weeks 9-12) | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | Weeks 9-12) | 
| Number of Subjects With Adequate Relief of IBS Symptoms at Least 50% of the Last 4 Weeks of Therapy | One of the weekly questions asked of subjects was, Did you have adequate relief of your IBS symptoms over the last week? Possible answers were Yes or No. | Weeks 9-12 | 
| Mean Pain BSS Score at Week 12 | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | Week 12 | 
| Mean Overall Severity BSS Score at Week 12 | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | Week 12 | 
| Mean Constipation BSS Score at Week 12 | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | Week 12 | 
| Mean Diarrhea BSS Score at Week 12 | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | Week 12 | 
| Mean Bloating BSS Score at Week 12 | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | Week 12 | 
| Number of Subjects With Greater Than or Equal to a 30 Point Change in Pain BSS Score | The Bowel Symptom Scale (BSS) consists of 5 questions, each with a 100 mm long Visual Analog Scale (VAS). The questions are regarding pain, bloating, constipation, diarrhea, and overall severity of Irritable Bowel Syndrome (IBS) symptoms. The VAS does not have any pre-set marks between the extremes of 0 for not present and 100 mm for very severe symptoms. The investigator measures the mark made by the participant in mm and records this for the value. | baseline, week 12 |