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

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02239926
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Diarrhea Predominant Irritable Bowel Syndrome	Drug: Ranolazine; Drug: Placebo	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Ranolazine on Gastrointestinal Motor Function and Pain in Patients With Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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.
Placebo Comparator: Placebo Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yuri A. Saito Loftus, Associate Professor of Medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02239926
• Other Study ID Numbers: 14-000581
• First Posted: Sep 15, 2014
• Last Update Posted: Mar 15, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Yuri A. Saito Loftus, Associate Professor of Medicine, Mayo Clinic: IBS-D
• Additional relevant MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea; Ranolazine

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at Mayo Clinic, Rochester Minnesota.
Pre-assignment Detail	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.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	tablet, 1000 mg twice daily for four weeks	Placebo
Period Title: Overall Study
STARTED	0	2
COMPLETED	0	1
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Ranolazine	Placebo	Total
Arm/Group Description	tablet, 1000 mg twice daily for four weeks	Placebo	Total of all reporting groups
Overall Participants	0	2	2
Age (participants) [Number]
<=18 years	0 NaN	0 0%
Between 18 and 65 years	2 Infinity	2 100%
>=65 years	0 NaN	0 0%
Gender (participants) [Number]
Female	2 Infinity	2 100%
Male	0 NaN	0 0%
Region of Enrollment (participants) [Number]
United States	2 Infinity	2 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Diarrhea Using the Bowel Symptom Score (BSS).
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	tablet, 1000 mg twice daily for four weeks	Placebo
Measure Participants	0	0

2. Secondary Outcome

Title	Mean Abdominal Pain
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	tablet, 1000 mg twice daily for four weeks	Placebo
Measure Participants	0	0

Adverse Events

Arm/Group Title	Ranolazine		Placebo
Arm/Group Description	tablet, 1000 mg twice daily for four weeks		Placebo
All Cause Mortality
	Ranolazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ranolazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Ranolazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/2 (0%)

Limitations/Caveats

The study was terminated early due to enrollment issues.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.