Look AHEAD: Action for Health in Diabetes

Study Overview
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Brief Summary
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The Look AHEAD study is a multi-center, randomized clinical trial to examine the long-term effects of a lifestyle intervention designed to achieve and maintain weight loss. The study will investigate the effects of the intervention on heart attacks, stroke and cardiovascular-related death in individuals with type 2 diabetes who are also overweight or obese.

Detailed Description
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Look AHEAD is examining, in overweight volunteers with type 2 diabetes, the long-term effects of an intensive lifestyle intervention program designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity. This program will be compared to a control condition involving a program of diabetes support and education. The primary hypothesis is that the incidence rate of the first post-randomization occurrence of a composite outcome, which includes cardiovascular death (including fatal myocardial infarction and stroke), non-fatal myocardial infarction, hospitalized angina, and non-fatal stroke, over a planned follow-up period of up to 13.5 years will be reduced among participants assigned to the Lifestyle Intervention compared to those assigned to the control condition, Diabetes Support and Education. Look AHEAD will also test for reductions in the incidence of three secondary composite outcomes and examine the effect of the intervention on cardiovascular disease risk factors, diabetes control and complications, general health, and quality of life, and psychological outcomes. The cost and cost-effectiveness of the Lifestyle Intervention relative to Diabetes Support and Education will be assessed. The Look AHEAD intensive lifestyle intervention ended September, 2012. Participants continue to be followed to determine the long-term effects of the intervention on health outcomes.

Official Title
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Look AHEAD: Action for Health in Diabetes

Conditions
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Diabetes, Myocardial Infarction, Stroke, Kidney Diseases, Bone Diseases, Dyslipidemia

Intervention / Treatment
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* Behavioral: Lifestyle Intervention
* Behavioral: Diabetes Support and Education


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Overweight BMI of 25 kg/m2 or greater If on insulin, BMI of 27 kg/m2 or greater Blood pressure less than 160/100 mmHg HbA1c less or equal to 11% Triglycerides less than 600 mg/dl Willingness to participate Exclusion Criteria: Unable or unwilling to give informed consent or communicate with local study staff. Current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder. Hospitalization for depression in past six months. Self-report of alcohol or substance abuse within the past twelve months. Current consumption of more than 14 alcoholic drinks per week. Current acute treatment or rehabilitation program for these problems. Plans to relocate to an area not served by Look AHEAD or travel plans that do not permit full participation in the study. Lack of support from primary care health provider or family members. Failure to complete the two-week run-in for dietary intake and exercise. Weight loss exceeding 10 lbs. in past three months. Current use of medications for weight loss. Self reported inability to walk two blocks. History of bariatric surgery, small bowel resection, or extensive bowel resection. Chronic treatment with systemic corticosteroids. Another member of the household is a participant or staff member in Look AHEAD. Currently pregnant or nursing. Cancer requiring treatment in the past five years, except for non-melanoma skin cancers or cancers that have clearly been cured. HIV positive (self-report), due to effects on weight and body composition of HIV and medications used to treat HIV. Active tuberculosis (self-report). Cardiovascular disease (heart attack or procedure within the past three months). Participation in a cardiac rehabilitation program within last three months. Stroke or history/treatment for transient ischemic attacks in the past three months. Pulmonary embolus in past six months. Unstable angina pectoris or angina pectoris at rest. A history of cardiac arrest. Complex ventricular arrhythmia at rest or with exercise (e.g., ventricular tachycardia). Uncontrolled atrial fibrillation (heart rate of 100 beats per minute or more). New York Heart Association (NYHA) Class III or IV congestive heart failure. Acute myocarditis, pericarditis or hypertrophic myocardiopathy. Clinically significant aortic stenosis. Left bundle branch block or cardiac pacemaker unless evaluated and cleared for participation by a cardiologist. Cardiac defibrillator. Heart transplant. History of aortic aneurysm of at least 7 cm in diameter or aortic aneurysm repair. Resting heart rate less than 45 beats per minute or greater than 100 beats per minute. Any abnormality during the maximum exercise stress test that indicates that it would be unsafe to participate in the Lifestyle Intervention. Angina pectoris. Significant ST segment depression at low levels of exercise. (ST segment is the flat, isoelectric section of the ECG between the end of the S wave (the J point) and the beginning of the T wave) Exercise induced ventricular arrhythmias. Abnormal hemodynamics, such as flat or decreasing systolic blood pressure with increasing workload. Those at moderate to high risk for cardiac complications during exercise. Those who are unable to self-regulate activity or understand the recommended activity level. Renal disease or dialysis. Chronic obstructive pulmonary disease that would limit ability to follow the protocol. Self-reported chronic hepatitis B or C or cirrhosis. Inflammatory bowel disease requiring treatment in past year. Cushing's syndrome. Acromegaly. Amputation of lower limbs as result of non-traumatic causes. Any major organ transplant.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 76 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lifestyle Intervention<br>Participants in the lifestyle intervention arm are offered individual and group sessions designed to help achieve and maintain weight loss. | Behavioral: Lifestyle Intervention<br>* The lifestyle intervention is implemented with individual supervision and group sessions and is aimed at achieving and maintaining at least a 7% decrease in weight from baseline and 175 minutes per week in physical activity. It is implemented during a four-year period with the most intensive application during the first year, less frequent attention during the next three years, and a minimum of twice yearly contacts during an extended follow-up period. To help participants achieve and maintain weight loss, a variety of diet strategies (e.g. prepared meals and liquid formula), exercise strategies, and optional weight loss medications are utilized based on a preset algorithm and participant progress.<br>|
| Active Comparator: Diabetes Support and Education<br>The diabetes support and education arm provides group sessions on diabetes management and social support. | Behavioral: Diabetes Support and Education<br>* Participants assigned to diabetes support and education are offered three sessions each year in diabetes management and social support.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First Occurrence of a Severe Cardiovascular Event | Number of participants with first on-study occurrence of one of the following major cardiovascular events: fatal and non-fatal myocardial infarctions and strokes, hospitalizations for angina, and cardiovascular deaths | up to 11 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First Occurrence of Cardiovascular Death, Myocardial Infarction, or Stroke | Number of participants with first occurrence of one of the following: cardiovascular death, myocardial infarction (fatal or nonfatal), or stroke (fatal or non-fatal) | up to 11 years | 
| First Occurrence of Death, Myocardial Infarction, or Hospitalized Angina | Number of participants with first occurrence of one of the following: death (all causes), myocardial infarction, stroke, or hospitalizations for angina | up to 11 years | 
| First Occurrence of Major Clinical Events | Number of participants with first occurrence of one of the following: death (all causes), myocardial infarction, stroke, hospitalization for angina, coronary artery bypass grafting, percutaneous coronary angioplasty, hospitalization for congestive heart failure, carotid endarterectomy, or peripheral vascular procedures such as bypass or angioplasty | up to 11 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Weight loss, Heart Attack, Heart disease, Lifestyle Intervention, Physical Fitness/Physical Activity, Psychosocial outcomes (e.g., depression, eating disorders), Bone Density