Lubiprostone and Mucus Secretion in Patients With Chronic Constipation

The Impact of Lubiprostone on Mucus Secretion in Asymptomatic Volunteers and Patients With Chronic Constipation

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.

Study Overview

• Status: Completed
• Conditions: Constipation
• Intervention / Treatment: Drug: lubiprostone; Drug: placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lubiprostone 24 mcg Twice a day; Both controls and patients with chronic constipation will receive 1 week of therapy with lubiprostone and one week of placebo.	Drug: lubiprostone; 24mcg twice a day (BID) 1 week; Other Names: Amitiza
Placebo Comparator: Placebo; Both controls and patients with chronic constipation will receive placebo pills twice daily for one week in cross over design	Drug: placebo; Placebo pills twice a day for one week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Mucus and Mucin Secretion in Patients With Chronic Constipation and in Controls.	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).	Measured after 1 week of lubiprostone and 1 week of placebo with 1 week of washout period in between.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Viscoelasticity of Gastric Secretion in Controls and Patients With Chronic Constipation.	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).	Measured after 1 week of lubiprostone therapy and compared to 1 week of placebo with 1 week of washout in between.

Collaborators and Investigators

• Sponsor: Texas Tech University Health Sciences Center, El Paso
• Investigators: Principal Investigator: Jerzy Sarosiek, MD, PhD, Texas Tech University Health Sciences Center

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: September 14, 2011
• First Submitted That Met QC Criteria: October 4, 2011
• First Posted (Estimate): October 6, 2011

Study Record Updates

• Last Update Posted (Actual): June 9, 2017
• Last Update Submitted That Met QC Criteria: May 5, 2017
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Chronic Constipation
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Lubiprostone
• Other Study ID Numbers: MSA-LUB-125; MSA-NC-LUB-125 (Other Grant/Funding Number: Takeda Pharmaceuticals)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No