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

Effect of Ranolazine on Gastrointestinal Motor Function and Pain in Patients With Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)

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

Study Overview

• Status: Terminated
• Conditions: Diarrhea Predominant Irritable Bowel Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Ranolazine

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Active Comparator: Ranolazine; tablet, 1000 mg twice daily for four weeks	Drug: Ranolazine; 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.; Other Names: Trade name Ranexa by Gilead Sciences.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline to 4 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Yuri A Saito, MD,MPH, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 11, 2014
• First Submitted That Met QC Criteria: September 12, 2014
• First Posted (Estimate): September 15, 2014

Study Record Updates

• Last Update Posted (Estimate): March 15, 2016
• Last Update Submitted That Met QC Criteria: February 16, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: IBS-D
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: 14-000581