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

• Drug: Pregabalin
  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.
  Other Name: Lyrica
• Drug: Placebo
  A matching placebo will be administered twice a day

• Active Comparator: Pregabalin

  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.

  Intervention: Drug: Pregabalin
• Placebo Comparator: Placebo
  Subjects randomized to this arm will receive placebo matching the study drug.
  Intervention: Drug: Placebo

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.

  1. Non-narcotic anti-pain medications (e.g. nonsteroidal antiinflammatory drug (NSAIDs), ultram, neurontin, etc.)
  2. Mexiletine, steroids, dextromethorphan.
  3. 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)