Copenhagen Study of Obese Patients With Ischemic Heart Disease Undergoing Low Energy Diet or Interval Training

Study Overview
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Brief Summary
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The purpose of the study is to make a head-to-head comparison of weight loss and interval training as methods of secondary prevention in overweight patients with ischemic heart disease.

Detailed Description
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In western countries 80 % of patients with ischemic heart disease (IHD) are overweight (BMI > 25). Weight loss using a low energy diet (LED, 800 - 1000 kcal/day) has been shown to induce a considerable weight loss in obese but otherwise healthy patients and to reduce the risk of cardiovascular disease and diabetes in these subjects. Additionally, a British study using a very low energy diet (VLED, 600 kcal/day) to obtain weight loss, has shown that subject with diagnosed type 2 diabetes had their blood glucose normalized after an 8 week VLED. However, the effect of LED has never been examined in overweight patients with IHD. Several studies have shown that patients with IHD have a beneficial effect of exercise training regarding mortality and reduction in cardiovascular risk factors. A Norwegian group has shown that aerobic interval training results in the biggest increase in maximal oxygen uptake (VO2max). A high VO2max is correlated to decreased mortality in patients with IHD. In conclusion, weight loss and exercise are known strategies in preventing progression of IHD and development of type 2 diabetes in these patients, however a head-to-head comparison of the two methods has never been made and it is unknown which intervention is the most effective in improving cardiovascular risk profile. Furthermore, several mechanisms behind the known beneficial effect of these interventions are unknown.

Official Title
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Copenhagen Study of Obese Patients With Ischemic Heart Disease Undergoing Low Energy Diet or Interval Training: A Randomized Clinical Trial

Conditions
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Ischemic Heart Disease, Obesity

Intervention / Treatment
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* Other: Interval Training
* Other: Weight Loss


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable Ischemic Heart Disease BMI 28 - 40 kg/m2 Exclusion criteria: Known Diabetes Mellitus Repeated Fasting plasma glucose ≥ 7 mmol/L or Hba1c > 7 % Severe or moderate valve disease Main stem stenosis Severe heart failure, Ejection Fraction < 35 % Physical or mental disability which are expected to prevent completion of intervention Severe Chronic obstructive Pulmonary Disease (COPD) (FEV1 < 50 % of expected) or asthma Active cancer Severe kidney (GFR < 40 ml/hour) or severe liver disease Severe ischemia or arrhythmias during exercise test 2. or 3. degree atrio-ventricular (AV) block, not protected by pacemaker Organised training more than 2 times a week prior to inclusion Significant weight loss or weight gain (> 5 %)3 month prior to inclusion Not able to comprehend written and oral informed consent Hormone treatment

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Weight Loss<br>12 weeks of Low Calorie Diet to obtain a 10 - 15 % weight loss. Followed by 40 weeks on a weight maintenance diet and interval training 2 times a week. | Other: Weight Loss<br>* Low calorie diet approx. 1000 kcal/day for 8 - 10 weeks to obtain a 10 - 15 % weight loss.<br>|
| Experimental: Interval Training<br>12 weeks of interval training 3 times a week followed by 40 weeks of interval training 2 times a week. | Other: Interval Training<br>* Interval training (IT) on an exercise bike 3 times a week, for the first 12 weeks, followed by 40 weeks of IT 2 times a week on exercise bike. Each training session consists of active intervals with a total duration of 16 minutes (durations intervals between 1 and 4 minutes) at 90% of maximal heart rate. Active intervals are separated by active pauses at 60% of maximal heart rate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Coronary Flow Reserve following the diet or training intervention and a maintenance period | Assessed by a non-invasive echocardiographic Doppler measurement | 0, 12 and 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Heart Rate Variability and silent ischemia following the diet or training intervention and a maintenance period | Assessed by Holter Monitoring for 24 - 48 hours | 0, 12 and 52 weeks | 
| Change in endothelial function following the diet or training intervention and a maintenance period | Using the Endopat 2000 from Itamar | 0, 12 and 52 weeks | 
| Change in systolic and diastolic function following the diet or training intervention and a maintenance period | Assessed by echocardiography resting and during physiological and medical stress. | 0, 12 and 52 weeks | 
| Change in body composition following the diet or training intervention and a maintenance period | Assessed by anthropometry, dual X-ray absorptiometry (DXA) (lean body mass, percentage adipose tissue) and abdominal MRI (liver fat, muscle fat, subcutaneous fat and visceral fat at the level of L3). | 0, 12 and 52 weeks | 
| Change in myocardial blood flow following the diet or training intervention and a maintenance period | Assessed by positron emission tomography of the heart | 0, 12 and 52 weeks | 
| Change in insulin action, beta cell function and incretin secretion following the diet or training intervention and a maintenance period | A Oral Glucose Tolerance Test is performed. | 0, 12 and 52 weeks | 
| Change in oxidized lipids and lipoprotein particle size following the diet or training intervention and a maintenance period |  | 0, 12 and 52 weeks | 
| Change in peak oxygen uptake (VO2max) following the diet or training intervention and a maintenance period | Assessed using a bicycle ergometer | 0, 12 and 52 weeks | 
| Change in blood pressure following the diet or training intervention and a maintenance period |  | 0, 12 and 52 weeks | 
| Change in inflammatory markers in urin, blood and adipose tissue following the diet or training intervention and a maintenance period |  | 0, 12 and 52 weeks | 
| Change in quality of life following the diet or training intervention and a maintenance period |  | 0, 12 and 52 weeks | 
| Change in ceramides, diacylglycerol og endocannabinoid (CB)-1 receptors in adipose tissue following the diet or training intervention and a maintenance period |  | 0, 12 and 52 weeks | 
| Change in hormones derived from adipose tissue following the diet or training intervention and a maintenance period |  | 0, 12 and 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interval Training, Weight Loss, Secondary Prevention, Rehabilitation, Cardiovascular Risk Factors