Lubiprostone and Mucus Secretion in Patients With Chronic Constipation

Phase 2

Completed

Conditions: Constipation

Interventions: Drug: lubiprostone
Drug: placebo

Registration Number: NCT01447849

Lead Sponsor: Texas Tech University Health Sciences Center, El Paso

Brief Summary: The investigators hypothesize that the symptoms of chronic constipation in some patients are developed due to diminished production and secretion of the alimentary tract mucus resulting in poor lubrication.

Therefore, the investigators assume that administration of lubiprostone may restore this lubrication impairment by stimulation of mucus production and secretion within the gastrointestinal tract.

Detailed Description: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Lubiprostone 24 mcg Twice a day	lubiprostone	Both controls and patients with chronic constipation will receive 1 week of therapy with lubiprostone and one week of placebo.
Placebo	placebo	Both controls and patients with chronic constipation will receive placebo pills twice daily for one week in cross over design

Primary Outcome Measures

Name	Time	Method
Change of Mucus and Mucin Secretion in Patients With Chronic Constipation and in Controls.	Measured after 1 week of lubiprostone and 1 week of placebo with 1 week of washout period in between.	The rate of mucus and mucin secretion(mg/hr) will be measured in gastric juice aspirated in basal conditions and during stimulation with pentagastrin after 1 week of therapy with lubiprostone (Active Comparator) and compared with 1 week of placebo administration (Placebo Comparator).

Secondary Outcome Measures

Name	Time	Method
Change in Viscoelasticity of Gastric Secretion in Controls and Patients With Chronic Constipation.	Measured after 1 week of lubiprostone therapy and compared to 1 week of placebo with 1 week of washout in between.	The viscoelasticity of gastric mucus(centipoises) was measured in gastric juice aspirated in basal conditions and during stimulation with pentagastrin after 1 week of therapy with lubiprostone (Active Comparator) and compared with 1 week of placebo administration (Placebo Comparator).