Constipation
Conditions
Keywords
Chronic Constipation
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).
Interventions
DRUGlubiprostone
24mcg twice a day (BID) 1 week
DRUGplacebo
Placebo pills twice a day for one week.
Sponsors
Texas Tech University Health Sciences Center, El Paso
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Recruitment details
During an entire recruitment time all patients signed their consent forms and participate in the study protocol within the specially designated clinical research room at Texas Tech University Health Sciences Center(TTUHSC), El Paso.
Pre-assignment details
Patients interested in our study were interviewed and examined 1 week before the 1st assigned after randomization medication was administered for one week of therapy. Subsequently, when patients finished their first week of medication, they had one week as of wash-out before the 2nd therapy in this cross-over design of our study protocol.
Participants by arm
| Arm | Count |
|---|---|
| Chronic Constipation(CC) Subjects on Lubiprostone Then Placebo Subjects with chronic constipation (CC) received 1 week of therapy with lubiprostone, then washed out for 1 week, then received 1 week of therapy with placebo.
lubiprostone: 24mcg twice a day (BID)for 1 week; placebo pill: twice a day (BID) for 1 week | 10 |
| Chronic Constipation (CC)Subjects on Placebo Then Lubiprostone Subjects with chronic constipation (CC)received 1 week of therapy with placebo,then washed out for 1 week, then received 1 week of therapy with lubiprostone.
placebo pill: twice a day (BID) for 1 week; lubiprostone: 24mcg twice a day (BID)for 1 week | 10 |
| Controls on Lubiprostone Then Placebo Control group received 1 week of therapy with lubiprostone, then washed out for 1 week, then received 1 week of therapy with placebo.
lubiprostone: 24mcg twice a day (BID)for 1 week; placebo pill: twice a day (BID) for 1 week | 10 |
| Controls on Placebo Then Lubiprostone Control group received 1 week of therapy with lubiprostone, then washed out for 1 week, then received 1 week of therapy with placebo.
lubiprostone: 24mcg twice a day (BID)for 1 week; placebo pill: twice a day (BID) for 1 week | 10 |
| Total | 40 |
Baseline characteristics
| Characteristic | Total | Chronic Constipation(CC) Subjects on Lubiprostone Then Placebo | Chronic Constipation (CC)Subjects on Placebo Then Lubiprostone | Controls on Lubiprostone Then Placebo | Controls on Placebo Then Lubiprostone |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 17 | 37 years STANDARD_DEVIATION 16 | 37 years STANDARD_DEVIATION 16 | 42 years STANDARD_DEVIATION 18 | 42 years STANDARD_DEVIATION 18 |
| Region of Enrollment United States | 40 participants | 10 participants | 10 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 30 Participants | 8 Participants | 7 Participants | 8 Participants | 7 Participants |
| Sex: Female, Male Male | 10 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
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).
Time frame: Measured after 1 week of lubiprostone and 1 week of placebo with 1 week of washout period in between.
Population: Number of participants was calculated to provide statistical power of 0.80 for detection of significance.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 mcg BID | Change of Mucus and Mucin Secretion in Patients With Chronic Constipation and in Controls. | Mucus Secretion in Chronic Constipation Subjects | 260 mg/hour | Standard Error 29 |
| Lubiprostone 24 mcg BID | Change of Mucus and Mucin Secretion in Patients With Chronic Constipation and in Controls. | Mucus Secretion in Controls | 229 mg/hour | Standard Error 33 |
| Lubiprostone 24 mcg BID | Change of Mucus and Mucin Secretion in Patients With Chronic Constipation and in Controls. | Mucin Secretion in Chronic Constipation Subjects | 99 mg/hour | Standard Error 14 |
| Lubiprostone 24 mcg BID | Change of Mucus and Mucin Secretion in Patients With Chronic Constipation and in Controls. | Mucin Secretion in Controls | 100 mg/hour | Standard Error 16 |
| Placebo | Change of Mucus and Mucin Secretion in Patients With Chronic Constipation and in Controls. | Mucin Secretion in Controls | 69 mg/hour | Standard Error 14 |
| Placebo | Change of Mucus and Mucin Secretion in Patients With Chronic Constipation and in Controls. | Mucus Secretion in Chronic Constipation Subjects | 133 mg/hour | Standard Error 16 |
| Placebo | Change of Mucus and Mucin Secretion in Patients With Chronic Constipation and in Controls. | Mucin Secretion in Chronic Constipation Subjects | 54 mg/hour | Standard Error 7 |
| Placebo | Change of Mucus and Mucin Secretion in Patients With Chronic Constipation and in Controls. | Mucus Secretion in Controls | 161 mg/hour | Standard Error 25 |
Secondary
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).
Time frame: Measured after 1 week of lubiprostone therapy and compared to 1 week of placebo with 1 week of washout in between.
Population: To provide 0.80 statistical power for detection of significance.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 mcg BID | Change in Viscoelasticity of Gastric Secretion in Controls and Patients With Chronic Constipation. | Basal viscosity in chronic constipation subjects | 21.61 Centipoises | Standard Error 2.95 |
| Lubiprostone 24 mcg BID | Change in Viscoelasticity of Gastric Secretion in Controls and Patients With Chronic Constipation. | Basal viscosity in controls | 12.78 Centipoises | Standard Error 2.53 |
| Lubiprostone 24 mcg BID | Change in Viscoelasticity of Gastric Secretion in Controls and Patients With Chronic Constipation. | Pentagastrin-Stimulated viscosity in CC | 14.96 Centipoises | Standard Error 3 |
| Lubiprostone 24 mcg BID | Change in Viscoelasticity of Gastric Secretion in Controls and Patients With Chronic Constipation. | Pentagastrin-Stimulated viscosity in Controls | 10.58 Centipoises | Standard Error 2.2 |
| Placebo | Change in Viscoelasticity of Gastric Secretion in Controls and Patients With Chronic Constipation. | Pentagastrin-Stimulated viscosity in Controls | 7.84 Centipoises | Standard Error 1.71 |
| Placebo | Change in Viscoelasticity of Gastric Secretion in Controls and Patients With Chronic Constipation. | Basal viscosity in chronic constipation subjects | 6.34 Centipoises | Standard Error 1.01 |
| Placebo | Change in Viscoelasticity of Gastric Secretion in Controls and Patients With Chronic Constipation. | Pentagastrin-Stimulated viscosity in CC | 4.59 Centipoises | Standard Error 1.2 |
| Placebo | Change in Viscoelasticity of Gastric Secretion in Controls and Patients With Chronic Constipation. | Basal viscosity in controls | 9.41 Centipoises | Standard Error 1.74 |