Effect of Lubiprostone on Methanogenesis and Bowel Function in Chronic Constipation.
Condition: Chronic Constipation, Methanogenesis
MeSH terms: Constipation
Intervention: Lubiprostone; Lubiprostone Control
Intervention description: Colonic transit study performed and stool/symptom diaries will be reviewed. Eligible subjects will be given a lactulose breath test and randomized to Lubiprostone or placebo. Treatment group receives 24 mcg Lubiprostone twice daily and placebo group receives pills (identical in appearance to the study drug) for one month. Subjects will be asked to maintain a daily stool/symptom diary for duration of the study. In the middle of the study a research coordinator will call the subjects to take questions/concerns and record adverse events. Lactulose breath test will be repeated, constipation questionnaire filled out, colon transit study performed.; Colonic transit study performed and stool/symptom diaries will be reviewed. Eligible subjects will be given a lactulose breath test and randomized to Lubiprostone or placebo. Treatment group receives 24 mcg Lubiprostone twice daily and placebo group receives pills (identical in appearance to the study drug) for one month. Subjects will be asked to maintain a daily stool/symptom diary for duration of the study. In the middle of the study a research coordinator will call the subjects to take questions/concerns and record adverse events. Lactulose breath test will be repeated, constipation questionnaire filled out, colon transit study performed.
Intervention MeSH terms: Lubiprostone
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Lubiprostone, a chloride channel activator, has been shown to improve symptoms of chronic
      constipation, largely by enhancing chloride-rich intestinal fluid secretion. Whether
      Lubiprostone has effects on colonic methanogenesis is not known. The investigators
      hypothesize that the effects of Lubiprostone may in part be due to its effects on altering
      colonic flora, particularly methanogenic flora.

      By altering the colonic stasis of stool and through more efficient clearance of digestive
      residue, the investigators anticipate that Lubiprostone may either inhibit or promote better
      excretion of methanogenic flora, and thereby decrease the gut load of methane producing
      bacteria. In turn, this may lead to enhanced colonic smooth muscle contraction and an
      increased rate of spontaneous bowel movements and reduction of constipation symptoms.

      The aim is to investigate the effects of Lubiprostone on intestinal methane production and
      bowel symptoms in patients with chronic constipation, by performing a randomized, double
      blind, placebo controlled study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Constipation as defined by Rome III criteria13. Patients must have symptoms > 3
             days/month for the past three months and report at least two of the following symptoms
             ≥ 25% of the time: straining, lumpy or hard stool, sensation of incomplete evacuation,
             sensation of anorectal obstruction/blockage, use of manual maneuvers, < 3 bowel
             movements/week. Also,they should have insufficient criteria for IBS, and only rarely
             loose stools without the use of laxatives.

          -  ≥ 3 ppm methane value at baseline1, 2(before sugar load).

        Exclusion Criteria:

          -  Patients taking drugs that are known to be constipating will be excluded or asked to
             discontinue medications for at least 2 weeks and reassessed. For example, we will
             recommend that patients taking calcium channel antagonists contact their respective
             primary care physicians to explore alternative medications for hypertension such as
             beta blockers or ACE-inhibitors. If the calcium channel antagonists are able to be
             discontinued, patients will be re-screened at least two weeks after the medications
             are discontinued. If patients no longer meet inclusion criteria, they will be excluded
             from the study. Patients who remain constipated will be eligible for enrollment.

          -  Patients with co-morbid illnesses such as severe cardiovascular disease, chronic renal
             failure, or those with previous gastrointestinal surgery except cholecystectomy and
             appendectomy

          -  Patients with neurologic diseases such as multiple sclerosis, strokes, spinal cord
             injuries, and those who have problems with cognizance, i.e. a mini-mental score of <15
             and/or are legally blind will be excluded.

          -  Women who are pregnant or are likely to conceive during the course of the study will
             be excluded. Urinary pregnancy tests will be performed on all women of child-bearing
             potential prior to enrollment and before any x-ray of the abdomen.

          -  Patients with Hirschsprung' s disease, or active local anorectal problems such as anal
             fissures, bleeding hemorrhoids, Crohn's, colitis, or colon cancer.

          -  Patients with alternating constipation and diarrhea and those who fulfill the Rome-III
             criteria for irritable bowel syndrome.

          -  Recent antibiotic use (last 6 weeks).

          -  Patients using laxatives, PEG or Tegaserod and unwilling to discontinue these
             medications at least 2 weeks prior to the study.