Ranolazine, Ethnicity and the Metabolic Syndrome (REMS)

Ranolazine, Ethnicity and the Metabolic Syndrome - REMS Study

The purpose of this study is to measure the effect of ranolazine on ETT (exercise treadmill test) exercise duration in four ethnic subgroups with established coronary artery disease and risk factor(s) for the metabolic syndrome: Caucasian, African American, Southeast Asian and East Indian.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Metabolic Syndrome; Angina
• Intervention / Treatment: Drug: Ranolazine

Detailed Description

Studies have shown that various ethnic subgroups are at differential risk for both the development and progression of coronary artery disease. The East Indian population is one of the highest risk populations for coronary artery disease. Much of this increased risk is driven by the development and progression of diabetes.

Recent studies have shown that ranolazine has a favorable effect on glycemic control. In addition, it is an effective antianginal and antiarrhythmic agent.

The investigators propose a pilot study look at the safety, tolerability and efficacy of this agent in patients with established coronary artery disease (CAD) and risk factors for the metabolic syndrome from various ethnic backgrounds. In particular the investigators will focus on the Caucasian, African American, Southeast Asian and East Indian population.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Cumming, Georgia, United States, 30041
      • Atlanta Heart Specialist, LLC
    • Tucker, Georgia, United States, 30084
      • Atlanta Heart Specialists, LLC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Evidence of stable Coronary Artery Disease

   • MI > 30 days prior to enrollment
   • PCI > 30 days prior to enrollment
   • CABG > 30 days prior to enrollment
   • Angiography showing > 50% stenosis in a major vessel, branch or bypass graft > 30 days prior to enrollment

2. Metabolic Syndrome as evidenced by at least one of the following risk factors:

   • Abdominal Obesity (elevated waist circumference)

     • Men - waist circumference ≥ 40 inches (102 cm) Asians/Asian Americans ≥ 35.5 inches (90 cm)
     • Women - waist circumference ≥ 35 inches (88 cm) Asians/Asian Americans ≥ 31.5 inches (80 cm)

   • Atherogenic dyslipidemia (either one or both)

     • Triglycerides ≥ 150 mg/dL
     • Reduced HDL Men - HDL ≤ 40 mg/dL Women - HDL ≤ 50 mg/dL
   • Elevated Blood Pressure (equal to or greater than 130/85)
   • Elevated fasting glucose (equal to or greater than 100 mg/dL)
3. Symptoms of angina or a suspected angina equivalent (upper body chest pain, shortness of breath, fatigue)
4. Patient able to perform an exercise treadmill test (ETT)
5. Written informed consent
6. Age > 18 years old

Exclusion Criteria:

• Unstable coronary artery disease or revascularization within 30 days of enrollment.
• Patients who have a prolonged QTc interval (>500ms)
• Patients who have known severe liver disease
• Current or planned co-administration of strong CYP3A inhibitors (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir) OR CYP3A inducers (eg, rifampin, rifabutin, rifapentine, Phenobarbital, phenytoin, carbamazepine, and St. John's Wort) OR moderate CYP3A inhibitors (eg, diltiazem, verapamil, aprepitant, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products)
• Patients who are pregnant or lactating
• Patients who are likely to be noncompliant with study procedures
• Patients currently in a study, or within 30 days of participating in a study, of an investigational drug or device

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care
Active Comparator: Ranolazine; Ranolazine in addition to standard of care medical therapy	Drug: Ranolazine; Patients in the ranolazine arm would start with 500 mg po BID of ranolazine and be force titrated to 1gm po BID after 2 weeks. Down-titration would only be allowed for side effects. This would be on top of all standard medical therapy.; Other Names: Ranexa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise Duration	To measure the effect of ranolazine on ETT (exercise treadmill test) exercise duration in four ethnic subgroups with established coronary artery disease and risk factor(s) for the metabolic syndrome: Caucasian, African American, Southeast Asian and East Indian.	change from baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fasting glucose	To measure the effect ranolazine has on fasting blood glucose.	change from baseline to 6 months
Angina	To look at the effect of ranolazine on anginal episodes using the Seattle Angina Questionnaire (SAQ).	change from baseline to 6 months
Concomitant medications	To measure the impact of ranolazine on reducing concomitant medication therapy such as anti-arrhythmic agents, hypoglycemic agents, and nitrates.	change from baseline to 6 months
lipid profile	To measure the effect ranolazine has on lipid profile.	change from baseline to 6 months
HgbA1c	To measure the effect ranolazine has on hemoglobin A1c.	change from baseline to 6 months

Collaborators and Investigators

• Sponsor: Atlanta Heart Specialists, LLC
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Narendra Singh, MD, Atlanta Heart Specialists, LLC

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Anticipated): November 1, 2013

Study Registration Dates

• First Submitted: February 16, 2011
• First Submitted That Met QC Criteria: February 24, 2011
• First Posted (Estimate): February 25, 2011

Study Record Updates

• Last Update Posted (Estimate): July 11, 2013
• Last Update Submitted That Met QC Criteria: July 9, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Coronary Artery Disease, Angina, Metabolic Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease; Insulin Resistance; Hyperinsulinism; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Syndrome; Metabolic Syndrome; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: AHS-REMS-001