Diarrhea Predominant Irritable Bowel Syndrome
Conditions
Keywords
IBS-D
Brief summary
Will Ranolazine improve bowel function and abdominal pain in human subjects with IBS-D?
Detailed description
This is a randomized double-blind placebo-controlled pilot study that will use validated bowel questionnaires to evaluate the effects of ranolazine administered orally twice daily in patients with diarrhea predominant IBS (IBS-D). The study will consist of a 2 week run in period, followed by 4 weeks of treatment period with oral ranolazine 1000 mg twice daily. Primary endpoint of the study will be the average Bowel Symptom Scale (BSS) scores for diarrhea and adequate relief of IBS pain and discomfort are secondary end points.
Interventions
DRUGRanolazine
On January 31, 2006, ranolazine was approved for use in the United States by the Food and Drug Administration (FDA) for the treatment of chronic angina pectoris.
DRUGPlacebo
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Males and non-pregnant, non-breastfeeding females with established diagnosis of IBS-D by modified Rome III criteria (Abdominal Pain Intensity: weekly average of worst daily score of \>3.0 on a 0 to 10 point scale and Stool Consistency: at least one stool with a consistency of Type 5, 6 or 7 Bristol stool score on at least 2 days per week) * 18-70 years old * U.S. resident * English-speaking (to provide consent and complete questionnaires)
Exclusion criteria
* Structural or metabolic diseases/conditions that affect the gastrointestinal system * Unable to withdraw the following medications 48 hours prior to the study: * Drugs that alter GI transit including Lomotil, and bile acid binders such as cholestyramine, prokinetics (e.g. metoclopramide, cisapride and erythromycin), narcotics (e.g. oxycodone, morphine) and anticholinergics (dicyclomine, hyoscyamine). * Analgesic drugs including narcotics, NSAID, cyclooxygenase-2 ( COX2) inhibitors (celecoxib, rofecoxib, and valdecoxib) * GABAergic agents (baclofen) * Benzodiazepines (e.g. lorazepam, alprazolam, and diazepam). Low stable doses of thyroid replacement, estrogen replacement, and low dose aspirin for cardioprotection and birth control pills or depot injections are permissible. * Unable to withdraw the following medications, which are contraindications of ranolazine: * Strong Cytochrome P450, Family 3, Subfamily A (CYP3A) inhibitors (e.g. ketoconazole, clarithromycin, and nelfinavir) * CYP3A inducers (e.g. rifampin, phenobarbital, St. John's wort) * Female subjects who are pregnant or breastfeeding. * Current symptoms of severe depression, as measured by Hospital Anxiety And Depression Scale ( HADS) score greater than 15. * Clinical evidence (including physical exam, ECG, laboratory studies and review of the medical history) of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric, or other disease that interfere with the objectives of the study. * The Corrected QT Interval (QTc) \> 490 msec. * Active alcoholics not in remission or known substance abusers. * Liver cirrhosis * Patients with clinically significant hepatic disease. * Major cardiovascular events in the last 6 months. * Participation in another clinical trial (within 30 days). * Incarcerated.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Diarrhea Using the Bowel Symptom Score (BSS). | baseline to 4 weeks | BSS is a 100-mm visual analog scale for each symptom of Irritable Bowel Syndrome (IBS) (pain or discomfort, bloating, and diarrhea) with an overall severity score. Lower scores indicate symptoms are not present and higher scores indicate severe symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Abdominal Pain | baseline to 4 weeks | Daily abdominal pain intensity was rated using an 11-point (0-10) numeric rating scale, with 0 being no pain, and 10 being the worst pain imaginable. Participants were asked to rate their worst abdominal pain over the past 24 hours. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled at Mayo Clinic, Rochester Minnesota.
Pre-assignment details
2 subjects were screen failures and were not randomized. 1 subject signed informed consent, but the study was suspended prior to that subject's randomization.
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine tablet, 1000 mg twice daily for four weeks | 0 |
| Placebo Placebo | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 participants | 0 participants |
| Age, Categorical >=65 years | 0 participants | 0 participants |
| Age, Categorical Between 18 and 65 years | 2 participants | 2 participants |
| Gender Female | 2 participants | 2 participants |
| Gender Male | 0 participants | 0 participants |
| Region of Enrollment United States | 2 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 2 |
| serious Total, serious adverse events | 0 / 0 | 0 / 2 |
Outcome results
Primary
Change From Baseline in Diarrhea Using the Bowel Symptom Score (BSS).
BSS is a 100-mm visual analog scale for each symptom of Irritable Bowel Syndrome (IBS) (pain or discomfort, bloating, and diarrhea) with an overall severity score. Lower scores indicate symptoms are not present and higher scores indicate severe symptoms.
Time frame: baseline to 4 weeks
Population: The one subject who completed the study did not have complete data, so no analysis was performed. Study was terminated due to difficulty with enrollment.
Secondary
Mean Abdominal Pain
Daily abdominal pain intensity was rated using an 11-point (0-10) numeric rating scale, with 0 being no pain, and 10 being the worst pain imaginable. Participants were asked to rate their worst abdominal pain over the past 24 hours.
Time frame: baseline to 4 weeks
Population: The one subject who completed the study did not have complete data, so no analysis was performed. Study was terminated due to difficulty with enrollment.