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

• To compare the effect of Pregabalin and placebo on self-reported overall and individual BSS scores [ Time Frame: Last 4 weeks of treatment ] [ Designated as safety issue: No ]
• compare effect of Pregabalin and placebo on adequate relief of IBS pain or discomfort at least 50% of the time [ Time Frame: During the last 4 weeks of therapy ] [ Designated as safety issue: No ]
• To compare effect of Pregabalin and placebo on overall and individual BSS scores [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• To compare the effect of Pregabalin and placebo on the proportion of patients with at least 3 point changes in 11 point pain and IBS scores [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

This study is being done to see if Lyrica helps people with irritable bowel syndrome, otherwise known as "IBS". 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 IBS-related conditions such as fibromyalgia.

• Drug: Pregabalin (Lyrica)
  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 (Lyrica)
  Pregabalin (Lyrica) is an FDA-approved prescription medication that was initially developed at Northwestern University and was approved in the European Union in 2004. It has been shown in several clinical trials to effectively treat patients with epilepsy, diabetic neuropathy pain, and post-herpetic neuralgia pain. It is relatively inexpensive compared to other IBSD medications and has a low side-effect profile. To date, no study has been performed in the United States examining the clinical effects of Pregabalin in IBS patients.
  Intervention: Drug: Pregabalin (Lyrica)
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Established diagnosis of 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
• 18-70 years of age
• 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, celiac sprue, chronic pancreatitis or pancreatic insufficiency, scleroderma, chronic intestinal pseudo-obstruction, bacterial overgrowth, recent (<6 months) intestinal bacterial/protozoal/ parasitic infections, HIV, fecal incontinence, small bowel or colonic resection, pelvic floor dysfunction, paraplegia or quadriplegia); Known alternative/concurrent gastrointestinal diagnosis (e.g. Crohn's disease, ulcerative colitis, microscopic colitis, celiac sprue, chronic pancreatitis or pancreatic insufficiency, scleroderma, chronic intestinal pseudo-obstruction, bacterial overgrowth, recent (<6 months) intestinal bacterial/protozoal/ parasitic infections, HIV, fecal incontinence, small bowel or colonic resection, pelvic floor dysfunction, paraplegia or quadriplegia)
• Current symptoms of severe depression, as measured by Hospital Anxiety and Depression Scale (HADS) score >=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:

  • ACE inhibitors (e.g. Zestril, Altace, Lotensin)
  • Rosiglitazone (Avandia) or Pioglitazone (Actos)
  • Narcotic anti-pain medications (e.g. oxycodone, morphine)
  • Anti-anxiety medications (e.g. lorazepam, alprazolam, diazepam)
  • Antidepressants (including TCAs, SSRIs, and SNRIs)

• 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. 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)