Bone Diseases, Diabetes, Dyslipidemia, Kidney Diseases, Myocardial Infarction, Stroke
Conditions
Keywords
Diabetes, Weight loss, Heart Attack, Heart disease, Lifestyle Intervention, Physical Fitness/Physical Activity, Psychosocial outcomes (e.g., depression, eating disorders), Bone Density
Brief summary
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
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.
Interventions
BEHAVIORALLifestyle Intervention
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.
BEHAVIORALDiabetes Support and Education
Participants assigned to diabetes support and education are offered three sessions each year in diabetes management and social support.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Nursing Research (NINR)
National Institute on Minority Health and Health Disparities (NIMHD)
Office of Research on Women's Health (ORWH)
Centers for Disease Control and Prevention
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 76 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| First Occurrence of a Severe Cardiovascular Event | up to 11 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| First Occurrence of Cardiovascular Death, Myocardial Infarction, or Stroke | up to 11 years | Number of participants with first occurrence of one of the following: cardiovascular death, myocardial infarction (fatal or nonfatal), or stroke (fatal or non-fatal) |
| First Occurrence of Death, Myocardial Infarction, or Hospitalized Angina | up to 11 years | Number of participants with first occurrence of one of the following: death (all causes), myocardial infarction, stroke, or hospitalizations for angina |
| First Occurrence of Major Clinical Events | up to 11 years | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lifestyle Intervention Participants in the lifestyle intervention arm are offered individual and group sessions designed to help achieve and maintain weight loss.
Lifestyle Intervention: 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. | 2,570 |
| Diabetes Support and Education The diabetes support and education arm provides group sessions on diabetes management and social support.
Diabetes Support and Education: Participants assigned to diabetes support and education are offered three sessions each year in diabetes management and social support. | 2,575 |
| Total | 5,145 |
Baseline characteristics
| Characteristic | Lifestyle Intervention | Diabetes Support and Education | Total |
|---|---|---|---|
| Age, Continuous | 58.55 years STANDARD_DEVIATION 6.77 | 58.85 years STANDARD_DEVIATION 6.86 | 58.70 years STANDARD_DEVIATION 6.81 |
| Ankle/Brachial Index<0.90 | 64 Participants | 88 Participants | 152 Participants |
| Body mass index | 35.89 kg/m^2 STANDARD_DEVIATION 6.01 | 36.00 kg/m^2 STANDARD_DEVIATION 5.76 | 35.95 kg/m^2 STANDARD_DEVIATION 5.88 |
| Diastolic blood pressure | 69.93 mmHg STANDARD_DEVIATION 9.55 | 70.40 mmHg STANDARD_DEVIATION 9.72 | 70.17 mmHg STANDARD_DEVIATION 9.63 |
| Duration of diabetes | 6.77 years STANDARD_DEVIATION 6.66 | 6.82 years STANDARD_DEVIATION 6.42 | 6.80 years STANDARD_DEVIATION 6.54 |
| Family history of diabetes | 1622 Participants | 1723 Participants | 3345 Participants |
| Fasting plasma glucose | 152.19 mg/dl STANDARD_DEVIATION 44.71 | 154.04 mg/dl STANDARD_DEVIATION 46.5 | 153.12 mg/dl STANDARD_DEVIATION 45.6 |
| HDL Cholesterol | 43.48 mg/dl STANDARD_DEVIATION 11.83 | 43.47 mg/dl STANDARD_DEVIATION 11.81 | 43.47 mg/dl STANDARD_DEVIATION 11.82 |
| Height | 167.22 cm STANDARD_DEVIATION 9.59 | 167.27 cm STANDARD_DEVIATION 9.86 | 167.25 cm STANDARD_DEVIATION 9.72 |
| Hemoglobin A1c% | 7.25 percentage of hemoglobin STANDARD_DEVIATION 1.14 | 7.31 percentage of hemoglobin STANDARD_DEVIATION 1.2 | 7.28 percentage of hemoglobin STANDARD_DEVIATION 1.17 |
| History of Cardiovascular Disease (CVD) | 373 Participants | 353 Participants | 726 Participants |
| Hypertension | 2063 Participants | 2069 Participants | 4132 Participants |
| LDL Cholesterol | 112.36 mg/dl STANDARD_DEVIATION 32.21 | 112.23 mg/dl STANDARD_DEVIATION 32.3 | 112.29 mg/dl STANDARD_DEVIATION 32.25 |
| Maximal MET Value | 7.21 kcal/kg/hour STANDARD_DEVIATION 1.95 | 7.18 kcal/kg/hour STANDARD_DEVIATION 1.99 | 7.19 kcal/kg/hour STANDARD_DEVIATION 1.97 |
| Maximal MET Value at 80% Heart Rate | 5.17 kcal/kg/hour STANDARD_DEVIATION 1.53 | 5.10 kcal/kg/hour STANDARD_DEVIATION 1.54 | 5.13 kcal/kg/hour STANDARD_DEVIATION 1.53 |
| Metabolic syndrome | 2387 Participants | 2415 Participants | 4802 Participants |
| Plasma creatinine | 0.82 mg/dl STANDARD_DEVIATION 0.2 | 0.82 mg/dl STANDARD_DEVIATION 0.2 | 0.82 mg/dl STANDARD_DEVIATION 0.2 |
| Race/Ethnicity, Customized Race / ethnicity African American / Black | 398 Participants | 405 Participants | 803 Participants |
| Race/Ethnicity, Customized Race / ethnicity American Indian / Alaskan Native | 131 Participants | 129 Participants | 260 Participants |
| Race/Ethnicity, Customized Race / ethnicity Asian / Pacific Islander | 29 Participants | 21 Participants | 50 Participants |
| Race/Ethnicity, Customized Race / ethnicity Hispanic | 338 Participants | 337 Participants | 675 Participants |
| Race/Ethnicity, Customized Race / ethnicity Other/Mixed/Unknown | 56 Participants | 55 Participants | 111 Participants |
| Race/Ethnicity, Customized Race / ethnicity White | 1618 Participants | 1628 Participants | 3246 Participants |
| Region of Enrollment United States | 2570 participants | 2575 participants | 5145 participants |
| Sex: Female, Male Female | 1524 Participants | 1534 Participants | 3058 Participants |
| Sex: Female, Male Male | 1046 Participants | 1041 Participants | 2087 Participants |
| Systolic blood pressure | 128.19 mmHg STANDARD_DEVIATION 17.26 | 129.45 mmHg STANDARD_DEVIATION 17.09 | 128.82 mmHg STANDARD_DEVIATION 17.17 |
| Total cholesterol | 191.33 mg/dl STANDARD_DEVIATION 38.16 | 190.65 mg/dl STANDARD_DEVIATION 37.04 | 190.99 mg/dl STANDARD_DEVIATION 37.59 |
| Triglycerides | 181.96 mg/dl STANDARD_DEVIATION 117.69 | 179.94 mg/dl STANDARD_DEVIATION 117.92 | 180.95 mg/dl STANDARD_DEVIATION 117.78 |
| Waist Circumference | 113.80 cm STANDARD_DEVIATION 14.35 | 114.06 cm STANDARD_DEVIATION 13.55 | 113.93 cm STANDARD_DEVIATION 13.95 |
| Weight | 100.54 kg STANDARD_DEVIATION 19.65 | 100.86 kg STANDARD_DEVIATION 18.83 | 100.7 kg STANDARD_DEVIATION 19.24 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 174 / 2,570 | 202 / 2,575 |
| other Total, other adverse events | 2,493 / 2,570 | 2,488 / 2,575 |
| serious Total, serious adverse events | 639 / 2,570 | 596 / 2,575 |
Outcome results
Primary
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
Time frame: up to 11 years
Population: Intent to Treat, all randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lifestyle Intervention | First Occurrence of a Severe Cardiovascular Event | 403 Participants |
| Diabetes Support and Education | First Occurrence of a Severe Cardiovascular Event | 418 Participants |
p-value: 0.5195% CI: [0.83, 1.09]Regression, Cox
Secondary
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)
Time frame: up to 11 years
Population: Intent to treat, all randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lifestyle Intervention | First Occurrence of Cardiovascular Death, Myocardial Infarction, or Stroke | 267 Participants |
| Diabetes Support and Education | First Occurrence of Cardiovascular Death, Myocardial Infarction, or Stroke | 283 Participants |
p-value: 0.4295% CI: [0.79, 1.1]Regression, Cox
Secondary
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
Time frame: up to 11 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lifestyle Intervention | First Occurrence of Death, Myocardial Infarction, or Hospitalized Angina | 496 Participants |
| Diabetes Support and Education | First Occurrence of Death, Myocardial Infarction, or Hospitalized Angina | 529 Participants |
p-value: 0.2395% CI: [0.82, 1.05]Regression, Cox
Secondary
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
Time frame: up to 11 years
Population: Intent to treat, all randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lifestyle Intervention | First Occurrence of Major Clinical Events | 577 Participants |
| Diabetes Support and Education | First Occurrence of Major Clinical Events | 600 Participants |
p-value: 0.2995% CI: [0.84, 1.05]Regression, Cox