Effects of Lubiprostone on Gastrointestinal Transit & pH in Irritable Bowel Syndrome (IBS) With Constipation

Inclusion criteria

• Males or females >18 years of age
• Meet Rome III criteria for IBS[2]:

• Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with 2 or more of the following:

• Improvement with defecation
• Onset associated with a change in frequency
• Onset associated with a change in form (appearance) of stool
• *Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis
• Fulfill the Rome III stool consistency criteria for IBS-C[2]

• Hard or lumpy stools for >25% of bowel movements
• Loose (mushy) or watery stools for <25% of bowel movements
• Capable of independently completing all requirements of the study including returning for required visits
• Able to provide written informed consent for study participation
• Willing to discontinue prohibited medications during study participation
• Documentation of a normal colonoscopy within last 5 years if over age 50 years (or sigmoidoscopy if less than age 50)
• Documentation of normal thyroid stimulating hormone(TSH) level, complet blood count (CBC) and electrolyte panel within prior 3 years
• Females of childbearing potential must have a negative urine or serum pregnancy test at screening
• Females of childbearing potential must use an effective means of contraception during the course of the study

• Hormonal (oral, injectable, implantable, cervical/vaginal rings or patches)
• Double-barrier (condoms and/or diaphragm with spermicides) or intrauterine devices provided under the care of a health care professional
• Abstinence, in this case documentation of counseling will be recorded

Exclusion criteria

• Unable to understand or provide written informed consent
• Pregnant or nursing
• Patients with IBS-D, IBS-M or unsubtyped IBS by Rome III criteria[2]
• IBS with diarrhea (IBS-D)

• Loose (mushy) or watery stools for >25% of bowel movements
• Hard or lumpy stools for <25% of bowel movements
• Mixed IBS (IBS-M)

• Hard or lumpy stools >25% of bowel movements
• Loose (mushy) or watery stools for >25% of bowel movements
• Unsubtyped IBS

• Insufficient abnormality of stool pattern to meet criteria for IBS-C, IBS-D or IBS-M
• Documented allergy or intolerance to lubiprostone
• Failure of balloon expulsion test

• Inability to expel 50cc balloon within 1 minute
• Use of drugs known to affect gastrointestinal motility

• Laxatives (stable doses of fiber taken for minimum of 4 weeks will be allowed)

Osmotic laxatives:

Magnesium hydroxide, Polyethylene glycol,Lactulose, Sorbitol

Stimulant laxatives:

Bisacodyl, Anthraquinones (senna), Misoprostol

• Prokinetic agents:

Metoclopramide, domperidone, erythromycin

• Anti-diarrheal agents:

Loperamide, Diphenoxylate, Bismuth

• Anti-spasmotics:

Dicyclomine, Hyoscyamine

• Opioid, narcotic, opioid/narcotic-containing analgesics:

Morphine, Hydrocodone, Codeine, Methadone, Propoxyphene

• Probiotics
• Systemic antibiotics within last 3 months
• Recently initiated antidepressants (stable dose for >2 months for non-GI conditions will be allowed)
• Benzodiazepines * Subjects taking prohibited medications will be required to stop these at the screening visit and remain off of them until completion of the study.
• Initiation of dietary changes potentially altering bowel transit within 4 weeks
• Comorbid medical problems that may affect gastrointestinal transit or motility

• Previous surgery involving the stomach, small bowel or colon (prior appendectomy, cholecystectomy, polypectomy allowed)
• Previous history of small bowel obstruction for any reason
• History of any gastrointestinal malignancy
• History of dyssynergic defecation
• Unexplained nausea and vomiting
• History of inflammatory bowel disease (Crohn's or ulcerative colitis)
• History of microscopic colitis (lymphocytic or collagenous colitis)
• History of Hirschsprung's disease
• Severe or complicated diverticular disease
• Chronic pancreatitis
• History of celiac disease
• History of eating disorders (anorexia nervosa or bulimia)
• Cirrhosis
• Chronic hepatitis B or C infection
• HIV infection
• Diabetes
• Systemic sclerosis (scleroderma)
• Amyloidosis
• Untreated thyroid disease
• Chronic pulmonary disease
• Severe renal insufficiency or renal failure
• Current or recent history (within last 6 months) of:

Diverticulitis, Duodenal or gastric ulcer, Acute pancreatitis, Ileus

• Contraindications to SmartPill® (in addition to above):

Cardiac pacemaker, defibrillator, or other implanted electromagnetic device, Known Zenker's diverticulum, Dysphagia