Generalized Anxiety Disorder, Irritable Bowel Syndrome
Conditions
Keywords
IBS, Irritable Bowel Syndrome, GAD, Generalized Anxiety Disorder
Brief summary
The investigators propose to evaluate the effectiveness of duloxetine in treating subjects with both Irritable Bowel Syndrome (IBS) and Generalized Anxiety Disorder (GAD). The investigators hypothesize that duloxetine as a single therapeutic agent will effectively target pain and other core symptoms of IBS as well as GAD in this patient population with both conditions.
Detailed description
Generalized Anxiety Disorder (GAD) is commonly associated with Irritable Bowel Syndrome(IBS). The etiology of IBS remains unknown and it is often refractory to treatment. Duloxetine has demonstrated efficacy in the treatment of GAD as well as other pain disorders including fibromyalgia and diabetic neuropathy. We plan to study 30 subjects with diagnoses of IBS and GAD between the ages of 18 and 65 years. There will be a single-blind placebo-run-in for the first 2 weeks, followed by open-label duloxetine for 12 weeks flexibly titrated to 120 mg/day. Subjects will be informed that they will receive placebo for 2 weeks during the trial. All study visits will be at Allegheny General Hospital Department of Psychiatry. The study consists of a total of nine office visits.
Interventions
DRUGDuloxetine
All subjects will receive single-blind placebo for the first two weeks, and then duloxetine for the next 12 weeks, followed by an up to 2 week taper off of the duloxetine. After 2 weeks of placebo daily, subjects will receive 30 mg per day of duloxetine for two weeks, then titrated up to 60 mg per day of duloxetine at week 2. A dosage decrease to 30 mg daily is permittable after week 2. This will be a flexible dose study with doses of duloxetine progressively increasing at weeks 4 (90 mg daily) and 6 (120 mg daily) in conjunction with CGI-I scores, to reach 120 mg daily or the maximum tolerated dose, if less than 120 mg daily at Week 12. There will be a post-taper follow up appointment at Week 14. Of Note: Amendment IRB Approved 6/14/11 Study Ending at Week 12 with removal of Week 14 visit as part of study.
Sponsors
West Penn Allegheny Health System
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18-65 years of age * Active IBS diagnosis by a gastroenterologist * Generalized Anxiety Disorder diagnosed by DSM-IV TR criteria and the Mini International Neuropsychiatric Interview for the DSM-IV (Mini) * No changes in any non study medication once starting the study
Exclusion criteria
* Current diagnoses of Major Depressive Disorder, Panic Disorder, Social Phobia, Post Traumatic Stress Disorder, Obsessive Compulsive Disorders, Eating Disorders, Somatoform Disorders, Drug or alcohol abuse or dependence, or severe personality disorder * Lifetime history of any Bipolar Disorder or Psychotic Disorder * Concurrent GI disorders falling outside of Rome III Functional GI disorders * Pregnant women or sexually active female subjects not using medically acceptable method of contraception * Current suicidal ideation * Unstable medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression Scale | endpoint [12 weeks] | The scale consists of two parts the first part being Severity of Illness and the second part is Global Improvement. We report the Global improvement scale. The Global Improvement is a 1-7 change scale of global improvement since inclusion in the project ranging with 1 very much improved, 4 no change, and 7 very much worse. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Anxiety Rating Scale | endpoint [12 weeks] | The HAM-A is a 14 question scale with five responses. Responses range from 0 not present to 4 very severe. The total score ranges from 0 to 56. Higher values represent a worse outcome. |
| Irritable Bowel Syndrome-Quality of Life Scale | endpoint [12 weeks] | The IBS-QOL consists of 34 items, each with a five-point response scale. Ratings range from 1 not at all to 5 extremely or a great deal Higher responses on the scale indicate worse outcome. A minimal total score would be 34, maximum 170. |
| Irritable Bowel Syndrome Severity Scoring System | endpoint [12 weeks] | This is a 4 item Likert scale with each assessment being 100 mm scored from measuring from 0 to 400. Higher numbers indicate worse outcome. |
Participant flow
Recruitment details
Subjects were referred by a gastroenterologist who had Irritable Bowel Syndrome and anxiety.
Pre-assignment details
Two participants were considered screen failures and were not entered into the placebo run in phase.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm every subject had a two week placebo run in followed by 12 weeks treatment intervention with Duloxetine. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 12 Weeks Duloxetine Treatment Phase | Protocol Violation | 1 |
| 12 Weeks Duloxetine Treatment Phase | Withdrawal by Subject | 2 |
| Two Week Placebo Run in | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment Arm |
|---|---|
| Age, Continuous | 42.54 years STANDARD_DEVIATION 12.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Clinical Global Impression Scale
The scale consists of two parts the first part being Severity of Illness and the second part is Global Improvement. We report the Global improvement scale. The Global Improvement is a 1-7 change scale of global improvement since inclusion in the project ranging with 1 very much improved, 4 no change, and 7 very much worse.
Time frame: endpoint [12 weeks]
Population: per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm | Clinical Global Impression Scale | 2.64 scores on a scale | Standard Deviation 0.5 |
Secondary
Hamilton Anxiety Rating Scale
The HAM-A is a 14 question scale with five responses. Responses range from 0 not present to 4 very severe. The total score ranges from 0 to 56. Higher values represent a worse outcome.
Time frame: endpoint [12 weeks]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm | Hamilton Anxiety Rating Scale | 9.75 scores on a scale | Standard Deviation 4.5 |
Secondary
Irritable Bowel Syndrome-Quality of Life Scale
The IBS-QOL consists of 34 items, each with a five-point response scale. Ratings range from 1 not at all to 5 extremely or a great deal Higher responses on the scale indicate worse outcome. A minimal total score would be 34, maximum 170.
Time frame: endpoint [12 weeks]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm | Irritable Bowel Syndrome-Quality of Life Scale | 81.73 scores on a scale | Standard Deviation 19.25 |
Secondary
Irritable Bowel Syndrome Severity Scoring System
This is a 4 item Likert scale with each assessment being 100 mm scored from measuring from 0 to 400. Higher numbers indicate worse outcome.
Time frame: endpoint [12 weeks]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm | Irritable Bowel Syndrome Severity Scoring System | 187.09 scores on a scale | Standard Deviation 54.05 |