Effects of Ranolazine and Exercise on Daily Physical Activity Trial

Study Overview
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Brief Summary
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The primary objective is to assess whether the increased angina threshold on ranolazine and subsequent higher training intensity will result in improved exercise tolerance and oxygen consumption; and greater than that observed with exercise training on placebo. The study team anticipates the chronic exercise improvements with ranolazine will be incrementally higher than the acute effects provided by ranolazine alone and demonstrated in previous trials. Key secondary objectives include the acute ranolazine and chronic exercise plus ranolazine effects on total daily energy expenditure (TDEE) and angina-related quality of life.

Official Title
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Effects of Ranolazine and Exercise on Daily Physical Activity Trial

Conditions
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Chronic Stable Angina

Intervention / Treatment
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* Drug: Ranolazine
* Behavioral: Aerobic Exercise
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented CAD diagnosis Stable angina ≥ 3 months Exclusion Criteria: Class III or IV heart failure Myocardial Infarction or coronary revascularization procedure within 2 months QT interval > 500ms or prescribed medication known to prolong the QTc interval Contraindicated Medications Metformin dose > 1700mg/day Class Ia, Ic and III anti-arrhythmics CYP3A inhibitors Simvastatin >20mg/day Severe renal disease (< 30ml/min creatinine clearance) Currently on dialysis Lack of transportation to the exercise and testing facilities Implanted pacemaker that is not rate responsive
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ranolazine plus Exercise<br>Ranolazine 1000mg pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold. | Drug: Ranolazine<br>* Comparison of Ranolazine 1000mg twice per day versus placebo twice per day<br>* Other names: Renexa;Behavioral: Aerobic Exercise<br>* Aerobic exercise 3 times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold (heart rate at which angina symptoms began on the stress test)<br>|
| Placebo Comparator: Placebo plus Exercise<br>Placebo pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold. | Behavioral: Aerobic Exercise<br>* Aerobic exercise 3 times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold (heart rate at which angina symptoms began on the stress test)<br>Drug: Placebo<br>* Comparison of placebo twice per day vs. Ranolazine 1000mg twice per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peak Oxygen Consumption (VO2 Max) | This test involves exercising on a treadmill or bike to maximal exertion, during which the subject's breathing and oxygen consumption are measured. Under a set study protocol, treadmill or bike workload will increase every minute until the participant either chooses to end the test or the study personnel choose to end the test for safety purposes. | Baseline, Week 2 and Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Treatment Satisfaction as Measured by the Seattle Angina Questionnaire | The Treatment Satisfaction scale is one of five scales of the Seattle Angina Questionnaire. The possible range of scores is 0 to 100, with higher scores indicating better quality of life. | Baseline, Week 2 and Week 14 | 
| Change in Total Daily Energy Expenditure | Total daily physical activity is measured via Actigraph GT3X accelerometers. Accelerometers will be worn for 7 days pre-drug, post-drug/pre-exercise (week 4) and again in the final month of the exercise intervention (week 13) | Week 1, Week 4 and Week 14 |