Clinical trial NCT02239926: Effect of Ranolazine on Gastrointestinal Motor Function and Pain in Patients With IBS-D
Official title: Effect of Ranolazine on Gastrointestinal Motor Function and Pain in Patients With Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Diarrhea Predominant Irritable Bowel Syndrome
Keywords: IBS-D
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2014-09-15
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Diarrhea Using the Bowel Symptom Score (BSS).
timeFrame: baseline to 4 weeks
Secondary outcomes:
measure: Mean Abdominal Pain
timeFrame: baseline to 4 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Yuri A Saito, MD,MPH
role: PRINCIPAL_INVESTIGATOR
References: