Constipation, Diabetes
Conditions
Keywords
Constipation, Diabetes, Lubiprostone, Amitiza, African Americans
Brief summary
The investigators will recruit a total of 136 diabetic men and women with constipation into this study from both The Emory Clinic and The Atlanta Veteran's Administration Hospital. The investigators will track spontaneous bowel movements defined as a bowel movement in 24 hours after initiation of study drug (SBMs) in all patients two weeks before treatment with lubiprostone as well as measure baseline colonic transit using the Smartpill pH capsule. Colon transit reflects that rate of colonic peristalsis and movement of stool through the large bowel. Patients will receive either lubiprostone 24 micrograms (mcg) orally twice a day for 8 weeks or placebo. Primary and secondary endpoints will be the number of SBMs/week and colonic transit time as measured by the Smartpill capsule, respectively. The number of SBMs/week will be evaluated at 0, 2, 4 and 8 weeks after initiation of therapy. The investigators will over-sample African American patients to achieve approximately 50% enrollment of this group. In a subanalysis, the investigators will assess response to treatment between the general population and African Americans. We hypothesize that lubiprostone will significantly increase the number of SBMs as well as decrease colonic transit time and improve quality of life in constipated diabetic patients compared with placebo.
Detailed description
Diabetes mellitus (DM) is very common in the United States, and the incidence as well as prevalence of this disease are increasing. DM is not only a risk factor for cardiovascular and pulmonary conditions, but is also linked with several digestive complications. Among digestive complaints, constipation occurs in approximated two-thirds of patients with DM, making constipation the most common gastrointestinal (GI) complaint among type 2 diabetics. Consequently, these patients suffer abdominal pain, bloating, and have a lower health related quality of life when compared with patients without DM and GI symptoms.Constipated individuals may be reluctant to eat on a regular schedule which may worsen glycemic control as well as the symptoms related to an underlying diabetic enteropathy. Effective therapies for constipation are limited and there is little data evaluating the treatment of constipation, specifically in diabetic patients. Lubiprostone has been shown to be superior to placebo in increasing the number of spontaneous bowel movements (SBMs) in patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). However, lubiprostone has not been previously studied in diabetics suffering with constipation. Furthermore, other prokinetic pharmacotherapeutics targeted toward constipated patients with diabetes mellitus type 2 are lacking. African Americans have the highest rate of DM compared with other ethnic groups in the Unites States. Furthermore, constipation is more prevalent in African Americans compared with other minority groups. However, there is little data evaluating the prevalence of constipation and the response to treatment in African Americans. Therefore, more information regarding the severity of symptoms, differences in bowel patterns, colonic transit, and response to therapy is important to improving the management of constipation in this group. Hence, in a subanalysis, we will study whether the responsiveness of African American patients to lubiprostone differs from that of the general population. Given the dearth of information on the effectiveness of lubiprostone in diabetics, who have a particularly strong need for alternative safe and effective treatments for constipation, we propose to assess the effectiveness of lubiprostone in constipated diabetic men and women. This is a randomized double- blind placebo controlled trial of lubiprostone in the treatment of constipation in diabetic patients.
Interventions
DRUGLubiprostone
Lubiprostone will be given as 24 mcg orally twice a day.
DRUGPlacebo
A matched placebo pill will be given twice a day for 8 weeks.
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diabetic patients with constipation. * Patient must be on stable oral or subcutaneous hypoglycemic medication for 6 months.
Exclusion criteria
* Acute infections * Ischemic bowel syndrome * Gastrointestinal obstruction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks | The average number of spontaneous bowel movements calculated per week from baseline to 8 weeks was recorded. The number of spontaneous bowel movements was recorded by the subjects in a daily stool diary and the weekly average was calculated. Spontaneous bowel movements are bowel movements within a 24 hour period independent of rescue medication use within the previous week. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy, Measured by the Duration of Colonic Transit Time as Measured by the SmartPill pH Capsule | Baseline, 4 weeks | The duration of colonic transit time in hours was measured by the SmartPill pH Capsule. Colonic transit time is the time interval from the cecal entry of the capsule to anal expulsion and was measured in hours. |
| Number of Subjects With Daily Abdominal Discomfort | 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks | The number of subjects experiencing abdominal discomfort was recorded weekly. |
| Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Screening, 8 weeks | The difference in the scores on the self-reported Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire. The quality of life is measured by the by the overall scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire, a validated 28-item questionnaire measuring quality of life as it pertains to constipation. The 28 items are grouped into four subscales, 1) worries and concerns, 2) physical discomfort, 3) psychosocial discomfort, and 4) satisfaction. A 5-point Likert response scale, ranging from 0 (Not at all/None of the time) to 4 (Extremely/ All of the time), is used. The subscale scores vary from 0 to 4 and the total (global) score ranges from 0 to 4. A lower score indicates better quality of life (QOL). |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from The Emory Clinic and The Atlanta Veterans Administration Hospital from August 2011 to September 2014.
Pre-assignment details
121 subjects were enrolled in the study; there were 4 Screen Failures, 22 drop outs prior to randomization and 19 subjects were Early Terminations. 76 subjects were randomized and underwent a two-week wash-out period during which they did not take any laxatives.
Participants by arm
| Arm | Count |
|---|---|
| Lubiprostone Subjects with diabetes and constipation received 24 mcg of lubiprostone orally twice a day for 8 weeks. | 37 |
| Placebo Subjects with diabetes and constipation received a placebo pill twice a day for 8 weeks. | 39 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of funding, drug not available | 3 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Lubiprostone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 39 Participants | 76 Participants |
| Region of Enrollment United States | 37 participants | 39 participants | 76 participants |
| Sex: Female, Male Female | 23 Participants | 27 Participants | 50 Participants |
| Sex: Female, Male Male | 14 Participants | 12 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 37 | 25 / 39 |
| serious Total, serious adverse events | 0 / 37 | 0 / 39 |
Outcome results
Primary
Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week
The average number of spontaneous bowel movements calculated per week from baseline to 8 weeks was recorded. The number of spontaneous bowel movements was recorded by the subjects in a daily stool diary and the weekly average was calculated. Spontaneous bowel movements are bowel movements within a 24 hour period independent of rescue medication use within the previous week.
Time frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks
Population: Two subjects in the Lubiprostone arm did not complete the daily stool diary at baseline. No data was analyzed for these two subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 1 week | 4.85 spontaneous bowel movements | Standard Deviation 5.27 |
| Lubiprostone | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 2 weeks | 3.81 spontaneous bowel movements | Standard Deviation 5.6 |
| Lubiprostone | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 3 weeks | 5.76 spontaneous bowel movements | Standard Deviation 4.99 |
| Lubiprostone | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 4 weeks | 4.12 spontaneous bowel movements | Standard Deviation 4.63 |
| Lubiprostone | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 5 weeks | 5.28 spontaneous bowel movements | Standard Deviation 4.1 |
| Lubiprostone | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 6 weeks | 4.52 spontaneous bowel movements | Standard Deviation 5.37 |
| Lubiprostone | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 7 weeks | 4.65 spontaneous bowel movements | Standard Deviation 5.27 |
| Lubiprostone | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 8 weeks | 5.30 spontaneous bowel movements | Standard Deviation 4.42 |
| Placebo | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 8 weeks | 2.63 spontaneous bowel movements | Standard Deviation 3.81 |
| Placebo | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 1 week | 1.40 spontaneous bowel movements | Standard Deviation 3.27 |
| Placebo | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 5 weeks | 3.03 spontaneous bowel movements | Standard Deviation 4.33 |
| Placebo | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 2 weeks | 2.41 spontaneous bowel movements | Standard Deviation 4.29 |
| Placebo | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 7 weeks | 3.46 spontaneous bowel movements | Standard Deviation 3.59 |
| Placebo | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 3 weeks | 3.11 spontaneous bowel movements | Standard Deviation 4.34 |
| Placebo | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 6 weeks | 3.23 spontaneous bowel movements | Standard Deviation 3.95 |
| Placebo | Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week | 4 weeks | 2.48 spontaneous bowel movements | Standard Deviation 3.68 |
Secondary
Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire
The difference in the scores on the self-reported Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire. The quality of life is measured by the by the overall scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire, a validated 28-item questionnaire measuring quality of life as it pertains to constipation. The 28 items are grouped into four subscales, 1) worries and concerns, 2) physical discomfort, 3) psychosocial discomfort, and 4) satisfaction. A 5-point Likert response scale, ranging from 0 (Not at all/None of the time) to 4 (Extremely/ All of the time), is used. The subscale scores vary from 0 to 4 and the total (global) score ranges from 0 to 4. A lower score indicates better quality of life (QOL).
Time frame: Screening, 8 weeks
Population: 7 subjects in the Lubiprostone arm and 7 subjects in the placebo arm did not complete the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire and therefore no data was analyzed for these subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone | Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Physical discomfort | -1.08 scores on a scale | Standard Deviation 0.71 |
| Lubiprostone | Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Worries and concerns | -0.88 scores on a scale | Standard Deviation 0.79 |
| Lubiprostone | Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Psychosocial discomfort | -0.72 scores on a scale | Standard Deviation 0.72 |
| Lubiprostone | Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Satisfaction | -1.28 scores on a scale | Standard Deviation 1.28 |
| Lubiprostone | Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Global Score | -0.91 scores on a scale | Standard Deviation 0.64 |
| Placebo | Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Satisfaction | -1.26 scores on a scale | Standard Deviation 1.43 |
| Placebo | Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Global Score | 1.19 scores on a scale | Standard Deviation 1.07 |
| Placebo | Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Physical discomfort | -1.22 scores on a scale | Standard Deviation 1.05 |
| Placebo | Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Psychosocial discomfort | -1.13 scores on a scale | Standard Deviation 1.07 |
| Placebo | Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire | Worries and concerns | -1.18 scores on a scale | Standard Deviation 1.29 |
Secondary
Efficacy, Measured by the Duration of Colonic Transit Time as Measured by the SmartPill pH Capsule
The duration of colonic transit time in hours was measured by the SmartPill pH Capsule. Colonic transit time is the time interval from the cecal entry of the capsule to anal expulsion and was measured in hours.
Time frame: Baseline, 4 weeks
Population: Intention to treat population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone | Efficacy, Measured by the Duration of Colonic Transit Time as Measured by the SmartPill pH Capsule | Baseline n=30; n=32 | 45.3 hours | Standard Deviation 25.7 |
| Lubiprostone | Efficacy, Measured by the Duration of Colonic Transit Time as Measured by the SmartPill pH Capsule | 4 weeks n=24; n=22 | 36.2 hours | Standard Deviation 28.1 |
| Placebo | Efficacy, Measured by the Duration of Colonic Transit Time as Measured by the SmartPill pH Capsule | Baseline n=30; n=32 | 40.9 hours | Standard Deviation 28.6 |
| Placebo | Efficacy, Measured by the Duration of Colonic Transit Time as Measured by the SmartPill pH Capsule | 4 weeks n=24; n=22 | 47.7 hours | Standard Deviation 27.7 |
Secondary
Number of Subjects With Daily Abdominal Discomfort
The number of subjects experiencing abdominal discomfort was recorded weekly.
Time frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks
Population: The number of participants in both arms was analyzed by Intention-to-Treat (ITT).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lubiprostone | Number of Subjects With Daily Abdominal Discomfort | 5 weeks (n=27; n=33) | 13 participants |
| Lubiprostone | Number of Subjects With Daily Abdominal Discomfort | 4 weeks (n=30; n=33) | 16 participants |
| Lubiprostone | Number of Subjects With Daily Abdominal Discomfort | 1 week (n=33; n=38) | 24 participants |
| Lubiprostone | Number of Subjects With Daily Abdominal Discomfort | 2 weeks (n=32; n=37) | 17 participants |
| Lubiprostone | Number of Subjects With Daily Abdominal Discomfort | 3 weeks (n=29; n=33) | 17 participants |
| Lubiprostone | Number of Subjects With Daily Abdominal Discomfort | 6 weeks (n=26; n=30) | 20 participants |
| Lubiprostone | Number of Subjects With Daily Abdominal Discomfort | 7 weeks (n=23; n=29) | 14 participants |
| Lubiprostone | Number of Subjects With Daily Abdominal Discomfort | 8 weeks (n=22; n=29) | 11 participants |
| Placebo | Number of Subjects With Daily Abdominal Discomfort | 8 weeks (n=22; n=29) | 15 participants |
| Placebo | Number of Subjects With Daily Abdominal Discomfort | 5 weeks (n=27; n=33) | 18 participants |
| Placebo | Number of Subjects With Daily Abdominal Discomfort | 3 weeks (n=29; n=33) | 21 participants |
| Placebo | Number of Subjects With Daily Abdominal Discomfort | 4 weeks (n=30; n=33) | 22 participants |
| Placebo | Number of Subjects With Daily Abdominal Discomfort | 7 weeks (n=23; n=29) | 16 participants |
| Placebo | Number of Subjects With Daily Abdominal Discomfort | 1 week (n=33; n=38) | 26 participants |
| Placebo | Number of Subjects With Daily Abdominal Discomfort | 6 weeks (n=26; n=30) | 14 participants |
| Placebo | Number of Subjects With Daily Abdominal Discomfort | 2 weeks (n=32; n=37) | 20 participants |