Irritable Bowel Syndrome
Conditions
Keywords
Irritable Bowel Syndrome, IBS, Savella, Milnacipran, Abdominal Pain
Brief summary
Purpose: The investigators are proposing to examine the use of Savella® (Milnacipran) for treating irritable bowel syndrome (IBS) in women. Participants: Eligible participants will meet the Rome III diagnostic criteria for IBS. Procedures: This study will observe patients treated with Savella® as well as patients treated with a placebo (pill with no active drug). The investigators will monitor and compare several patient and symptom related outcomes, as well as evaluate health related quality of life, psychological distress and related psychosocial measures to determine if the addition of Savella® improves clinical pain response as well as secondary outcomes including quality of life.
Detailed description
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized primarily by abdominal pain associated with bowel dysfunction. Like many other painful functional somatic syndromes (e.g. fibromyalgia) the pathophysiology of IBS includes abnormal responses to pain and dysregulation of brain-body pain pathways. IBS affects up to 10% of the population, is a leading reason for visits to gastroenterologists and primary care doctors, and, in the United States, annually accrues health care costs over $20 billion. In their practice the investigators use centrally acting agents to treat IBS. Historically, the investigators have used tricyclic antidepressants based on results of clinical trials, including our NIH funded trial on desipramine. Nonetheless, these agents can produce side effects that limit their full application. More recently the investigators have begun to use SNRIs because they have been shown to benefit for various pain syndromes like diabetic neuropathy, fibromyalgia. The initial impression is that Milnacipran helps improve IBS symptoms and global well being. There is now a need to systematically determine Milnacipran's value for IBS.
Interventions
DRUGMilnacipran
50mg Milnacipran PO, BID, for 6 weeks.
DRUGPlacebo
Inactive pill, identical in shape, size, and appearance to active drug, PO, BID.
Sponsors
Forest Laboratories
Spencer Dorn, MD, MPH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Meet Rome III criteria for IBS and have no red flags. * Must have had a colonoscopy within the previous 5 years to exclude inflammatory or other bowel disease * Be fluent and literate in English * Must either be of non-childbearing potential or agree to utilize approved birth control for the duration of the study
Exclusion criteria
* Diagnosis or treatment of any clinically symptomatic biochemical or structural abnormality of the GI tract within 6 months prior to screening, or active disease within 6 months prior to screening. * Any other diagnosis to explain the abdominal pain, * Clinical evidence of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematologic, neurologic, psychiatric or any disease that may interfere with the subject successfully completing the trial * Hepatic dysfunction (ALT \[SGPT\] or AST \[SGOT\] \>3 times the upper limit of normal) or renal impairment (serum creatinine \> 2mg/dL) * Has disease affecting electrolytes balance, such as SIADH with serum Sodium less than 130mmol/L * Any evidence of or treatment of malignancy (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected) within the previous year * Any surgery on the stomach, small intestine or colon, excluding appendectomy * A major psychiatric disorder (DSM-III-R or DSM-IV) including major depression or other psychoses that has required hospitalization in the last 1 year. * History of attempted suicide or uncontrolled bipolar disorder. * Currently using antidepressants for psychiatric conditions like major depression. Use of TCA or SSRI class antidepressant acceptable if being used specifically for treatment of bowel symptoms and patient is willing to taper off the medication * Previous use of Milnacipran or other SNRI antidepressant (duloxetine, venlafaxine, desvenlafaxine) * A diagnosis of seizure disorder * A diagnosis of glaucoma * Currently taking heparin or warfarin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pain Response | Twelve Weeks | Visual Analog Scale (VAS) scores (range 0-100 mm; 0 = none, 100 = worst pain) were recorded for pain before the beginning of the study, at 6 weeks of treatment and at the end visit i.e. 10 weeks. Ideally, VAS would have been administered at the 12th week; however, subject was terminated at the 10th week visit. A positive pain response (ie pain relief) was defined as \>30% decrease in the VAS score between baseline and the final study visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life ( IBS-QOL) | Six Weeks | After six weeks of treatment with Milnacipran, treatment groups were compared with placebo for clinically significant improvement in IBS-QOL. 11 point reduction in IBS-QOL compared to baseline was considered as clinically significant improvement. |
| Subject Self Reported Adequate Relief of Pain | Twelve Weeks | The study sought to determine if the Milnacipran arms had a greater proportion of adequate relief over the placebo group. Subjects were asked to answer 'yes' or 'no' as to whether or not they had adequate relief of pain due to irritable bowel syndrome. |
| Treatment Efficacy Questionnaire (TEQ) | Twelve Weeks | Treatment Efficacy Questionnaire is a measure of treatment effectiveness. The score ranges from 1 to 48, 1 is minimum score and 48 is the maximum score. The investigators was looking to see if the Milnacipran treatment groups have a higher proportion of subjects with significant improvement in efficacy, judged as a TEQ score of \>28, compared to placebo group. |
| Dose Related Incremental Benefit in Pain Reduction Based on VAS | 12 Weeks | The investigator was looking to see if, for group A, when increased from 50 mg BID to 100 mg BID there is significant improvement of pain scores i.e. 30% pain reduction, and for group C, if there was significant improvement of pain scores when switched from placebo to 50 mg BID of Milnacipran |
Countries
United States
Participant flow
Recruitment details
The subjects were recruited from community using University of North Carolina (UNC) mass email system, newspaper advertisement and UNC gastrointestinal (GI) clinic referral.
Pre-assignment details
Subjects undergo screening labs and questionnaires to make sure subjects are healthy and don't have any underlying conditions. Subjects who had clinically significant labs or Hospital Anxiety and depression scale(HADS)score more than 17 were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Group A (50mg - 100mg) Group A will begin treatment with Milnacipran 50mg BID (n=20) during Phase I and will be increased to 100mg BID during Phase II
Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks.
Milnacipran : Milnacipran, 100mg PO, BID, for six weeks | 1 |
| Group B (50mg x12) Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study.
Milnacipran : Milnacipran, 50mg PO BID for 12 weeks | 1 |
| Group C (Placebo - 50mg) Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II
Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks.
Placebo : Inactive pill, identical in shape, size, and appearance to active drug, PO, BID. | 0 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Study terminated | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Group B (50mg x12) | Group A (50mg - 100mg) | 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 | 1 Participants | 1 Participants | 2 Participants |
| Age, Continuous | 66 years STANDARD_DEVIATION 0 | 47 years STANDARD_DEVIATION 0 | 56.5 years STANDARD_DEVIATION 9.5 |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 0 |
Outcome results
Primary
Number of Participants With Pain Response
Visual Analog Scale (VAS) scores (range 0-100 mm; 0 = none, 100 = worst pain) were recorded for pain before the beginning of the study, at 6 weeks of treatment and at the end visit i.e. 10 weeks. Ideally, VAS would have been administered at the 12th week; however, subject was terminated at the 10th week visit. A positive pain response (ie pain relief) was defined as \>30% decrease in the VAS score between baseline and the final study visit.
Time frame: Twelve Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A (50mg - 100mg) | Number of Participants With Pain Response | 0 participants |
Secondary
Dose Related Incremental Benefit in Pain Reduction Based on VAS
The investigator was looking to see if, for group A, when increased from 50 mg BID to 100 mg BID there is significant improvement of pain scores i.e. 30% pain reduction, and for group C, if there was significant improvement of pain scores when switched from placebo to 50 mg BID of Milnacipran
Time frame: 12 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A (50mg - 100mg) | Dose Related Incremental Benefit in Pain Reduction Based on VAS | 0 percentage of participants |
Secondary
Quality of Life ( IBS-QOL)
After six weeks of treatment with Milnacipran, treatment groups were compared with placebo for clinically significant improvement in IBS-QOL. 11 point reduction in IBS-QOL compared to baseline was considered as clinically significant improvement.
Time frame: Six Weeks
Secondary
Subject Self Reported Adequate Relief of Pain
The study sought to determine if the Milnacipran arms had a greater proportion of adequate relief over the placebo group. Subjects were asked to answer 'yes' or 'no' as to whether or not they had adequate relief of pain due to irritable bowel syndrome.
Time frame: Twelve Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A (50mg - 100mg) | Subject Self Reported Adequate Relief of Pain | 0 percentage of participants |
Secondary
Treatment Efficacy Questionnaire (TEQ)
Treatment Efficacy Questionnaire is a measure of treatment effectiveness. The score ranges from 1 to 48, 1 is minimum score and 48 is the maximum score. The investigators was looking to see if the Milnacipran treatment groups have a higher proportion of subjects with significant improvement in efficacy, judged as a TEQ score of \>28, compared to placebo group.
Time frame: Twelve Weeks
Population: Only one subject was enrolled and was analyzed even though subject did not complete the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A (50mg - 100mg) | Treatment Efficacy Questionnaire (TEQ) | 0 percentage of subject with score >28 |