Effect of Ranolazine on Gastrointestinal Motor Function and Pain in Patients With IBS-D

Mayo Clinic

Status and phase

Terminated

Phase 3

Phase 2

Conditions

Diarrhea Predominant Irritable Bowel Syndrome

Treatments

Drug: Placebo

Drug: Ranolazine

Study type

Interventional

Funder types

Other

Identifiers

NCT02239926

14-000581

Details and patient eligibility

About

Will Ranolazine improve bowel function and abdominal pain in human subjects with IBS-D?

Full 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.

Enrollment

5 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.