Lubiprostone and Mucus Secretion in Patients With Chronic Constipation

Specific Aim 1. To test the effect of Lubiprostone, 24 mcg twice a day (BID) for 1 week, on
gastric mucus production in 20 asymptomatic volunteers and 20 patients with chronic
constipation in basal conditions (primary outcome).

Specific Aim 2. To explore the effect of Lubiprostone, 24 mcg twice a day (BID) for 1 week,
on gastric mucus production in 20 asymptomatic volunteers and 20 patients with chronic
constipation during stimulation of gastric secretion with pentagastrin, mimicking the
meal-stimulated conditions (primary outcome).

Specific Aim 3. To address the influence of Lubiprostone, 24 mcg twice a day (BID) for 1
week, on gastric mucin production, the major component of mucus, in 20 asymptomatic
volunteers and 20 patients with chronic constipation in basal conditions (primary outcome).

Specific Aim 4. To test the influence of Lubiprostone, 24 mcg twice a day (BID) for 1 week,
on gastric mucin production, the major component of mucus, in 20 asymptomatic volunteers and
20 patients with chronic constipation during stimulation of gastric secretion with
pentagastrin, mimicking the meal-stimulated conditions (primary outcome).

Specific Aim 5. To explore the impact of Lubiprostone, 24 mcg twice a day (BID) for 1 week,
on viscoelasticity of gastric mucus in 20 asymptomatic volunteers and 20 patients with
chronic constipation in basal conditions (secondary outcome).

Specific Aim 6. To address the impact of Lubiprostone, 24 mcg twice a day (BID) for 1 week,
on viscoelasticity of gastric mucus in 20 asymptomatic volunteers and 20 patients with
chronic constipation during stimulation of gastric secretion with pentagastrin, mimicking
the meal-stimulated conditions (secondary outcome).

Asymptomatic Volunteers:

Inclusion Criteria:

- 18-65 years of age

- Capable of and willing to give informed consent, and willing to comply with all study
requirements

Exclusion Criteria:

- Pregnancy or lactation

- Subjects unwilling to practice adequate contraception throughout the screening period
through 14 days after study termination

- Illegal use of illegal drugs

- Regular consumption of 2 or more drinks of alcohol per day

- Chronic non-steroidal anti- inflammatory drugs (NSAID) use

- Chronic use of H2 receptor antagonists or Proton Pump Inhibitors (PPIs) within 14
days prior to screening

- History of gastric of duodenal ulcer or chronic non-ulcer dyspepsia

- Positive Helicobacter pylori (H. pylori) serology

Patients with Chronic Constipation:

Inclusion Criteria:

- Age 18-65

- At least 6 months history of constipation. Constipation defined as: a. Less than
three complete spontaneous bowel movements per week and one or more of the following:
i) At least 25% of stools are very hard and/or hard stools ii) Sensation of
incomplete evacuation following at least 25% of bowel movements iii) Straining on at
least 25% of defecations The above criteria are only applicable to spontaneous bowel
movements. Patients who have no spontaneous bowel movements (bowel movements are
preceded by laxative intake) are considered constipated and are eligible for this
study

- For patients >= years of age, normal colonic anatomy as documented by colonoscopy,
double-contrast barium enema, or flexible sigmoidoscopy performed within the previous
5 years

Exclusion Criteria

- Pregnancy or lactation

- Subjects unwilling to practice adequate contraception throughout the period of
screening through 14 days after study termination

- Use of laxatives 3 days immediately prior to randomization (except fiber or bulking
agents)

- Use of any of the following drugs within 3 days prior to randomization a) Prokinetic
agents (tegaserod, domperidone, cisapride, metoclopramide, erythromycin, b)
Medications containing opiates c) Antispasmodic (e.g. atropine, hyoscyamine,
scopolamine, glycopyrrolate)

- Use of illegal drugs

- Regular consumption of 2 drinks of alcohol per day

- Chronic NSAIDs use

- Chronic use of H2 receptor antagonist or PPIs within 14 days prior to screening

- History of gastric or duodenal ulcer, Inflammatory bowel disease (IBD), or chronic
non-ulcer dyspepsia

- Diabetes mellitus (DM) type 1

- Parkinson's disease

- Existence of any medical condition that requires chronic therapy

- Positive H. pylori serology