Chronic Idiopathic Constipation
Conditions
Keywords
chronic constipation, constipation, idiopathic constipation, SmartPill, Wireless Motility Capsule, lubiprostone (Amitiza), small intestinal bacterial overgrowth
Brief summary
The purpose of this study is to determine if lubiprostone may change the rate of movement of food and activities in the stomach and intestines in subjects whose gastrointestinal (GI) tract is slower due to constipation. To be able to measure the time difference in the duration of transit of the FDA approved SmartPill capsule in all segments of gastrointestinal (GI) tract before and after exposure to lubiprostone. The investigators anticipate to capture the possibility to reduce/eliminate the small intestinal bacterial overgrowth in chronically constipated patients after administration of study drug- lubiprostone.
Detailed description
Lubiprostone is an effective treatment for chronic constipation. The mechanism of action of lubiprostone is through increasing fluid and mucus secretion and improving lubrication of the intestinal lumen. The effects of lubiprostone on gastrointestinal (GI) transit and small bacterial overgrowth (SIBO) have not been sufficiently explored. The current study was designed to investigate whether: (a) lubiprostone alters GI transit and (b) affects SIBO in constipated patients. Twenty nine female patients (mean age of 39 year: range 19-64) with chronic constipation received 2 weeks of lubiprostone (24 mcg b.i.d., P.O.). Stool consistency based on Bristol stool scale and the frequency of bowel movements were recorded. Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT), combined small & large bowel transit time (SLBTT) and whole gut transit time (WGT) were measured using wireless motility capsule. Small bacterial overgrowth (SIBO) status was assessed by the lactulose breath test.
Interventions
DRUGLubiprostone
24 mcg twice a day (BID) for 2 weeks.
Sponsors
Takeda Pharmaceuticals North America, Inc.
Texas Tech University Health Sciences Center, El Paso
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18-65 years old * At least a 6 months history of constipation. Constipation defined as follows: * Less than three complete spontaneous bowel movements per week and one or more of the following: 1. At least 25% of stools are very hard and/or hard stools 2. Sensation of incomplete evacuation following at least 25% of bowel movements. 3. 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 ≥ 50 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 the 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: * Prokinetic agents (tegaserod, domperidone, cisapride, metoclopramide, erythromycin). * Medication containing opiates. * Anti-spasmodic (e.g., atropine, hyoscyamine, scopolamine, glycopyrrolate). * Use of illegal drugs * Regular consumption of 2 drinks of alcohol per day. * Chronic nonsteroidal antiinflammatory drugs (NSAIDs) use * Chronic use of H2 receptor antagonist or proton pump inhibitors (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 * Chronic active diverticulosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Reduction (Hours and Minutes) of Gastric Emptying (GE), Small Bowel (SB), Large Bowel (LB) and Whole Gut (WG) Transits Measured by SmartPill in Chronically Constipated Patients Before and After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day. | Measured at baseline and 2 weeks after baseline. | The change in transit time (TT), in hours and minutes, of gastric emptying (GE), small bowel (SB), large bowel (LB) and whole gut (WG) measured by SmartPill in 29 patients with chronic constipation after taking lubiprostone 24 micrograms twice a day (BID) for 2 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Number of Bowel Movements in Chronically Constipated Patients After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day (BID). | Measured at baseline and 2 weeks after baseline | — |
| Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Measured at baseline and 2 weeks after baseline. | Changes in Time of GE, SB, LB and WG transits measured by SmartPill after 2 weeks of lubiprostone 24mcg BID in chronically constipated patients who increased stool frequency to ≥ 2 times increase per week vs. patients who increased stool frequency \< 2 times increase per week. |
| Changes in Number of Bowel Movements Per Week Changes GE, SB, LB and WG Transit Times Measured by SmartPill in Chronically Constipated Patients Treated for 2 Weeks With Lubiprostone 24mcg Twice a Day. | Measured at baseline and 2 weeks after baseline. | — |
| Elimination of Small Intestine Bacterial Overgrowth (SIBO) in Chronically Constipated Patients Treated With Lubiprostone 24mcg Twice a Day for 2 Weeks. | Measured at baseline and 2 weeks after baseline. | — |
Countries
United States
Participant flow
Recruitment details
Participants recruited from University of Kansas Medical Center, in Kansas City, KS from July 2008 to August 2009. Additional participants were recruited from Texas Tech University Health Sciences Center - El Paso, in El Paso, TX between April 2012 and November 2012.
Pre-assignment details
37 participants recruited; 37 screened, 8 excluded. 25 of those subjects participated in small intestinal bacterial overgrowth (SIBO) testing and analysis.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Due to the nature of this project, which did not include placebo, blinded portion of the investigation, all patients were exposed to study drug in a similar design. Lubiprostone 24 micrograms twice a day for 14 consecutive days was provided for qualified patients after all inclusionary criteria were met. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Could not swallow SmartPill | 2 |
| Overall Study | Did not meet inclusionary criteria | 2 |
| Overall Study | Technical malfunction of SmartPill data | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 39 years |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Time Reduction (Hours and Minutes) of Gastric Emptying (GE), Small Bowel (SB), Large Bowel (LB) and Whole Gut (WG) Transits Measured by SmartPill in Chronically Constipated Patients Before and After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day.
The change in transit time (TT), in hours and minutes, of gastric emptying (GE), small bowel (SB), large bowel (LB) and whole gut (WG) measured by SmartPill in 29 patients with chronic constipation after taking lubiprostone 24 micrograms twice a day (BID) for 2 weeks.
Time frame: Measured at baseline and 2 weeks after baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Time Reduction (Hours and Minutes) of Gastric Emptying (GE), Small Bowel (SB), Large Bowel (LB) and Whole Gut (WG) Transits Measured by SmartPill in Chronically Constipated Patients Before and After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day. | Gastric Emptying Time before treatment | 7.0 Hours | Standard Error 1.1 |
| All Participants | Time Reduction (Hours and Minutes) of Gastric Emptying (GE), Small Bowel (SB), Large Bowel (LB) and Whole Gut (WG) Transits Measured by SmartPill in Chronically Constipated Patients Before and After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day. | Small Bowel Transit Time before treatment | 5.9 Hours | Standard Error 1.1 |
| All Participants | Time Reduction (Hours and Minutes) of Gastric Emptying (GE), Small Bowel (SB), Large Bowel (LB) and Whole Gut (WG) Transits Measured by SmartPill in Chronically Constipated Patients Before and After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day. | Small & Large Bowel Transit Time before treatment | 56.7 Hours | Standard Error 8.7 |
| All Participants | Time Reduction (Hours and Minutes) of Gastric Emptying (GE), Small Bowel (SB), Large Bowel (LB) and Whole Gut (WG) Transits Measured by SmartPill in Chronically Constipated Patients Before and After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day. | Whole Gut Transit Time before treatment | 64.2 Hours | Standard Error 8.5 |
| All Participants | Time Reduction (Hours and Minutes) of Gastric Emptying (GE), Small Bowel (SB), Large Bowel (LB) and Whole Gut (WG) Transits Measured by SmartPill in Chronically Constipated Patients Before and After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day. | Gastric Emptying Time after treatment | 9.3 Hours | Standard Error 1.9 |
| All Participants | Time Reduction (Hours and Minutes) of Gastric Emptying (GE), Small Bowel (SB), Large Bowel (LB) and Whole Gut (WG) Transits Measured by SmartPill in Chronically Constipated Patients Before and After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day. | Small Bowel Transit Time after treatment | 4.5 Hours | Standard Error 0.4 |
| All Participants | Time Reduction (Hours and Minutes) of Gastric Emptying (GE), Small Bowel (SB), Large Bowel (LB) and Whole Gut (WG) Transits Measured by SmartPill in Chronically Constipated Patients Before and After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day. | Small & Large Bowel Transit Time after treatment | 43.2 Hours | Standard Error 4.6 |
| All Participants | Time Reduction (Hours and Minutes) of Gastric Emptying (GE), Small Bowel (SB), Large Bowel (LB) and Whole Gut (WG) Transits Measured by SmartPill in Chronically Constipated Patients Before and After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day. | Whole Gut Transit Time after treatment | 52.5 Hours | Standard Error 4.8 |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Changes in Number of Bowel Movements in Chronically Constipated Patients After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day (BID).
Time frame: Measured at baseline and 2 weeks after baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Changes in Number of Bowel Movements in Chronically Constipated Patients After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day (BID). | Bowel Movements after treatment | 4.6 number per week | Standard Error 0.4 |
| All Participants | Changes in Number of Bowel Movements in Chronically Constipated Patients After 2 Weeks of Therapy With Lubiprostone 24mcg Twice a Day (BID). | Bowel Movements before treatment | 1.9 number per week | Standard Error 0.1 |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Changes in Number of Bowel Movements Per Week Changes GE, SB, LB and WG Transit Times Measured by SmartPill in Chronically Constipated Patients Treated for 2 Weeks With Lubiprostone 24mcg Twice a Day.
Time frame: Measured at baseline and 2 weeks after baseline.
Population: Number of Bowel Movements per week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Changes in Number of Bowel Movements Per Week Changes GE, SB, LB and WG Transit Times Measured by SmartPill in Chronically Constipated Patients Treated for 2 Weeks With Lubiprostone 24mcg Twice a Day. | Bowel Movements before treatment | 1.8 number per week | Standard Error 0.1 |
| All Participants | Changes in Number of Bowel Movements Per Week Changes GE, SB, LB and WG Transit Times Measured by SmartPill in Chronically Constipated Patients Treated for 2 Weeks With Lubiprostone 24mcg Twice a Day. | Bowel Movements after treatment | 6.0 number per week | Standard Error 0.5 |
| Non-Responders | Changes in Number of Bowel Movements Per Week Changes GE, SB, LB and WG Transit Times Measured by SmartPill in Chronically Constipated Patients Treated for 2 Weeks With Lubiprostone 24mcg Twice a Day. | Bowel Movements before treatment | 2.1 number per week | Standard Error 0.2 |
| Non-Responders | Changes in Number of Bowel Movements Per Week Changes GE, SB, LB and WG Transit Times Measured by SmartPill in Chronically Constipated Patients Treated for 2 Weeks With Lubiprostone 24mcg Twice a Day. | Bowel Movements after treatment | 3.0 number per week | Standard Error 0.2 |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients.
Changes in Time of GE, SB, LB and WG transits measured by SmartPill after 2 weeks of lubiprostone 24mcg BID in chronically constipated patients who increased stool frequency to ≥ 2 times increase per week vs. patients who increased stool frequency \< 2 times increase per week.
Time frame: Measured at baseline and 2 weeks after baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Gastric Emptying Time after treatment | 11.6 Hours | Standard Error 2.9 |
| All Participants | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Small & Large Bowel Transit Time before treatment | 45.9 Hours | Standard Error 6.8 |
| All Participants | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Small Bowel Transit Time after treatment | 4.4 Hours | Standard Error 0.6 |
| All Participants | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Small Bowel Transit Time before treatment | 7.2 Hours | Standard Error 2.1 |
| All Participants | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Small & Large Bowel Transit Time after treatment | 32.0 Hours | Standard Error 4.3 |
| All Participants | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Whole Gut Transit Time before treatment | 55.5 Hours | Standard Error 6.3 |
| All Participants | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Whole Gut Transit Time after treatment | 43.7 Hours | Standard Error 4.6 |
| All Participants | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Gastric Emptying Time before treatment | 9.6 Hours | Standard Error 1.5 |
| Non-Responders | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Whole Gut Transit Time after treatment | 63.4 Hours | Standard Error 8.5 |
| Non-Responders | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Small & Large Bowel Transit Time before treatment | 70.1 Hours | Standard Error 17.3 |
| Non-Responders | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Gastric Emptying Time before treatment | 3.9 Hours | Standard Error 1.2 |
| Non-Responders | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Whole Gut Transit Time before treatment | 75.0 Hours | Standard Error 17.3 |
| Non-Responders | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Gastric Emptying Time after treatment | 6.4 Hours | Standard Error 2.1 |
| Non-Responders | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Small Bowel Transit Time after treatment | 4.5 Hours | Standard Error 0.5 |
| Non-Responders | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Small & Large Bowel Transit Time after treatment | 57.0 Hours | Standard Error 7.2 |
| Non-Responders | Changes in Time of GE, SB, LB and WG Transits Measured by SmartPill After 2 Weeks of Lubiprostone 24mcg BID in Chronically Constipated Patients. | Small Bowel Transit Time before treatment | 4.5 Hours | Standard Error 0.3 |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Elimination of Small Intestine Bacterial Overgrowth (SIBO) in Chronically Constipated Patients Treated With Lubiprostone 24mcg Twice a Day for 2 Weeks.
Time frame: Measured at baseline and 2 weeks after baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Elimination of Small Intestine Bacterial Overgrowth (SIBO) in Chronically Constipated Patients Treated With Lubiprostone 24mcg Twice a Day for 2 Weeks. | SIBO (+) participants before treatment | 17 participants |
| All Participants | Elimination of Small Intestine Bacterial Overgrowth (SIBO) in Chronically Constipated Patients Treated With Lubiprostone 24mcg Twice a Day for 2 Weeks. | SIBO (+) participants after treatment | 10 participants |
| All Participants | Elimination of Small Intestine Bacterial Overgrowth (SIBO) in Chronically Constipated Patients Treated With Lubiprostone 24mcg Twice a Day for 2 Weeks. | SIBO (+)→SIBO (-) participants after treatments | 7 participants |