Irritable Bowel Syndrome
Conditions
Keywords
IBS, irritable bowel syndrome, irritable bowel
Brief summary
We hypothesize that duloxetine treatment will be associated with improvement in symptoms of IBS, particularly abdominal pain, in individuals without comorbid major depressive disorder. During this 12-week, open-label, outpatient study, male and female subjects between the ages of 18 and 65 years who have been diagnosed with irritable bowel syndrome (IBS) will be treated with open-label duloxetine.
Detailed description
IBS is a chronic gastrointestinal disorder characterized by abdominal pain, altered bowel habits, and abdominal bloating for which no organic cause can be determined. Duloxetine has demonstrated efficacy in the treatment of depression as well as in several pain syndromes including diabetic peripheral neuropathy and fibromyalgia. We hypothesize that it will be a safe and efficacious treatment for the symptoms of IBS, in particular abdominal pain. We plan to study 15 male and female subjects between the ages of 18 and 65 years who have had gastrointestinal symptoms at least 2 days/week for greater than six months and who have been diagnosed with IBS by a physician. During the 12-week study, subjects will receive open-label duloxetine titrated up to 60mg/day. Subjects will be asked to complete a total of ten study visits during the 12-week study period. All study visits will be conducted at McLean Hospital.
Interventions
DRUGduloxetine
30mg oral duloxetine per day for one week, titrated up to 60mg per day at day 8, concluded by a one week taper period of 4 days of 30mg pills at the conclusion of the study, followed by 3 days on no medication (4+3 days=1 week), concluded with a post-taper follow-up appointment with a study physician.
Sponsors
Eli Lilly and Company
Mclean Hospital
Study design
Allocation
NON_RANDOMIZED
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 of age * Subjects must have been diagnosed with irritable bowel syndrome by a physician * Subjects must have had gastrointestinal symptoms for 2 or more days per week for \> 6 months
Exclusion criteria
* Lifetime history of bipolar disorder, psychotic disorder, or obsessive-compulsive disorder * Current (within past 6 months) diagnosis of major depressive disorder or substance abuse disorder * Active suicidal/homicidal ideation * Pregnant women or women of child-bearing potential not using an approved methods of contraception * Individuals with an unstable medical condition that in the opinion of the investigator would interfere with the interpretation of symptoms
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Abdominal Pain, as Determined by Daily Pain Diaries (Patterned After Item 3 From the Brief Pain Inventory; Cleeland and Ryan, 1994). | baseline and week 12 | Subjects rated abdominal pain daily on a scale of 0-10 (0 being no pain and 10 being worst pain). The pain score at each visit represented the mean score from all days since the previous visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Short Form McGill Pain Questionnaire | At each visit | The Short Form McGill Pain Questionnaire is a self-administered questionnaire that measures pain intensity experienced by the patient. Scores on 15 descriptors are rated on an intensity scale of 0-3 (with 0 being no pain to 3 being severe pain), and has an overall score of between 0-45, with 0 being no pain and 45 being worst possible pain. The primary analysis for this outcome was assessed at each visit with a longitudinal repeated-measures random regression analysis assessing the rate of change of the measure during the treatment period. The model for the mean included a term for time (modeled as a continuous variable) and the measure effect was the estimated change in the outcome at week 12. |
| Clinical Global Impression Scale | At each visit | The Clinical Global Impression Scale is a clinician-rated scale that evaluates the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The primary analysis for this outcome was assessed at each visit with a longitudinal repeated-measures random regression analysis assessing the rate of change of the measure during the treatment period. The model for the mean included a term for time (modeled as a continuous variable) and the measure effect was the estimated change in the outcome at week 12. |
| Hamilton Depression Rating Scale | At first visit only | The Hamilton Depression Rating Scale is a clinician-rated scale consisting of 17 questions designed to assess depressive symptoms. Scores of 0-7 are considered normal, 8-16 suggest mild depression, 17-23 moderate depression, and scores over 24 are indicative of severe depression. 52 is the maximum score. |
| Brief Pain Inventory | At each visit | The Brief Pain Inventory is a self-administered questionnaire used to evaluate the severity of a patient's pain and its interference with their life. Four items measure pain severity on a scale of 0-10, with 0 being absence of pain and 10 being severe pain. Seven items measure pain interference on a scale of 0-10, with 0 being absence of interference and 10 being severe interference. The sub scale of both sub scores ranges 0-40, with 0 indicating no pain/interference and 40 indicating severe pain/interference. The primary analysis for this outcome was assessed at each visit with a longitudinal repeated-measures random regression analysis assessing the rate of change of the measure during the treatment period. The model for the mean included a term for time (modeled as a continuous variable) and the measure effect was the estimated change in the outcome at week 12. |
| Irritable Bowel Syndrome-Quality of Life Scale | At baseline and week 12 | The Irritable Bowel Syndrome (IBS) Quality of Life Scale is a self-report quality of life measure specific to Irritable Bowel Syndrome that can be used to assess the impact of IBS and its treatment. There are 34 items summed and averaged for a total score between 0-100, with higher scores indicating better IBS specific quality of life. Each item measures one of eight sub scales - dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual, and relationships - and is rated on a scale of 1-5 indicating how much the subject agrees with the statement (1 is no agreement, 5 is extreme agreement). The primary analysis of this scale was an endpoint analysis of the change from baseline. |
| Sheehan Disability Scale | At baseline and week 12 | The Sheehan Disability Scale is a brief, 5-item self-report tool that assess functional impairment in work/school, social life, and family life. Scores range from 0-10 in each subset, with 0 being unimpaired and 10 being highly impaired. The primary analysis of this scale was an endpoint analysis of the change from baseline. |
| Hamilton Anxiety Rating Scale | At baseline and week 12 | The Hamilton Anxiety Rating Scale is a clinician-administered scale designed to assess the severity of symptoms of anxiety. There are 14 items, scored on a scale of 0 (not present) to 4 (severe). The total score range is 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity, and 25-30 moderate to severe. The primary analysis of this scale was an endpoint analysis of the change from baseline. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through advertisements
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine, 60 mg Daily Open-label duloxetine was administered for a duration of 12 weeks. Subjects received duloxetine 30 mg daily for 1 week followed by duloxetine 60 mg daily for 11 weeks. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
Baseline characteristics
| Characteristic | Duloxetine, 60 mg Daily |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 44.5 years STANDARD_DEVIATION 13.1 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Abdominal Pain, as Determined by Daily Pain Diaries (Patterned After Item 3 From the Brief Pain Inventory; Cleeland and Ryan, 1994).
Subjects rated abdominal pain daily on a scale of 0-10 (0 being no pain and 10 being worst pain). The pain score at each visit represented the mean score from all days since the previous visit.
Time frame: baseline and week 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Duloxetine, 60 mg Daily | Abdominal Pain, as Determined by Daily Pain Diaries (Patterned After Item 3 From the Brief Pain Inventory; Cleeland and Ryan, 1994). | -1.5 Units on a scale |
p-value: <0.001Mixed Models Analysis
Secondary
Brief Pain Inventory
The Brief Pain Inventory is a self-administered questionnaire used to evaluate the severity of a patient's pain and its interference with their life. Four items measure pain severity on a scale of 0-10, with 0 being absence of pain and 10 being severe pain. Seven items measure pain interference on a scale of 0-10, with 0 being absence of interference and 10 being severe interference. The sub scale of both sub scores ranges 0-40, with 0 indicating no pain/interference and 40 indicating severe pain/interference. The primary analysis for this outcome was assessed at each visit with a longitudinal repeated-measures random regression analysis assessing the rate of change of the measure during the treatment period. The model for the mean included a term for time (modeled as a continuous variable) and the measure effect was the estimated change in the outcome at week 12.
Time frame: At each visit
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Duloxetine, 60 mg Daily | Brief Pain Inventory | Average pain severity | -1.5 units on a scale |
| Duloxetine, 60 mg Daily | Brief Pain Inventory | Average pain interference | -1.6 units on a scale |
Comparison: Average pain severity statistical analysisp-value: <0.001Mixed Models Analysis
Comparison: Average pain interference statistical analysisp-value: <0.001Mixed Models Analysis
Secondary
Clinical Global Impression Scale
The Clinical Global Impression Scale is a clinician-rated scale that evaluates the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The primary analysis for this outcome was assessed at each visit with a longitudinal repeated-measures random regression analysis assessing the rate of change of the measure during the treatment period. The model for the mean included a term for time (modeled as a continuous variable) and the measure effect was the estimated change in the outcome at week 12.
Time frame: At each visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Duloxetine, 60 mg Daily | Clinical Global Impression Scale | -1.7 units on a scale |
p-value: <0.001Mixed Models Analysis
Secondary
Hamilton Anxiety Rating Scale
The Hamilton Anxiety Rating Scale is a clinician-administered scale designed to assess the severity of symptoms of anxiety. There are 14 items, scored on a scale of 0 (not present) to 4 (severe). The total score range is 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity, and 25-30 moderate to severe. The primary analysis of this scale was an endpoint analysis of the change from baseline.
Time frame: At baseline and week 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Duloxetine, 60 mg Daily | Hamilton Anxiety Rating Scale | -3.3 units on a scale |
p-value: 0.031Mixed Models Analysis
Secondary
Hamilton Depression Rating Scale
The Hamilton Depression Rating Scale is a clinician-rated scale consisting of 17 questions designed to assess depressive symptoms. Scores of 0-7 are considered normal, 8-16 suggest mild depression, 17-23 moderate depression, and scores over 24 are indicative of severe depression. 52 is the maximum score.
Time frame: At first visit only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine, 60 mg Daily | Hamilton Depression Rating Scale | 6.7 units on a scale | Standard Deviation 2.2 |
Secondary
Irritable Bowel Syndrome-Quality of Life Scale
The Irritable Bowel Syndrome (IBS) Quality of Life Scale is a self-report quality of life measure specific to Irritable Bowel Syndrome that can be used to assess the impact of IBS and its treatment. There are 34 items summed and averaged for a total score between 0-100, with higher scores indicating better IBS specific quality of life. Each item measures one of eight sub scales - dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual, and relationships - and is rated on a scale of 1-5 indicating how much the subject agrees with the statement (1 is no agreement, 5 is extreme agreement). The primary analysis of this scale was an endpoint analysis of the change from baseline.
Time frame: At baseline and week 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Duloxetine, 60 mg Daily | Irritable Bowel Syndrome-Quality of Life Scale | 14.8 units on a scale |
p-value: <0.001Mixed Models Analysis
Secondary
Sheehan Disability Scale
The Sheehan Disability Scale is a brief, 5-item self-report tool that assess functional impairment in work/school, social life, and family life. Scores range from 0-10 in each subset, with 0 being unimpaired and 10 being highly impaired. The primary analysis of this scale was an endpoint analysis of the change from baseline.
Time frame: At baseline and week 12
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Duloxetine, 60 mg Daily | Sheehan Disability Scale | Work/School | -2.5 units on a scale |
| Duloxetine, 60 mg Daily | Sheehan Disability Scale | Social | -1.8 units on a scale |
| Duloxetine, 60 mg Daily | Sheehan Disability Scale | Family | -2.2 units on a scale |
p-value: 0.004Mixed Models Analysis
p-value: 0.087Mixed Models Analysis
p-value: 0.006Mixed Models Analysis
Secondary
Short Form McGill Pain Questionnaire
The Short Form McGill Pain Questionnaire is a self-administered questionnaire that measures pain intensity experienced by the patient. Scores on 15 descriptors are rated on an intensity scale of 0-3 (with 0 being no pain to 3 being severe pain), and has an overall score of between 0-45, with 0 being no pain and 45 being worst possible pain. The primary analysis for this outcome was assessed at each visit with a longitudinal repeated-measures random regression analysis assessing the rate of change of the measure during the treatment period. The model for the mean included a term for time (modeled as a continuous variable) and the measure effect was the estimated change in the outcome at week 12.
Time frame: At each visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Duloxetine, 60 mg Daily | Short Form McGill Pain Questionnaire | -2.37 units on a scale |
p-value: 0.001Mixed Models Analysis