|June 21, 2001
|March 15, 2011
|December 2014 (final data collection date for primary outcome measure)
|The primary outcome is the aggregate occurrence of severe cardiovascular events. [ Time Frame: 11.5 years ] [ Designated as safety issue: No ]
|Complete list of historical versions of study NCT00017953 on ClinicalTrials.gov Archive Site
|Look AHEAD: Action for Health in Diabetes
|Look AHEAD: Action for Health in Diabetes
The Look AHEAD study is a multicenter, 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.
Research has shown that weight loss has many short-term benefits, such as improvements in blood pressure, but we do not know if attempts to lose weight over the long term are beneficial. Some studies even suggest that losing weight may lead to health problems such as gall bladder disease and bone loss. Look AHEAD will help us understand the long-term effects of weight loss on health, and see if it helps reduce heart attacks and strokes.
We hope to learn the long-term benefits and risks of a program designed to achieve and maintain weight loss. The study will consist of two groups of volunteers. One group will be asked to eat fewer calories and increase their physical activity. This group will be compared to a second group who will receive diabetes support and education. Both groups will receive medical monitoring. In addition to heart attacks and stroke, Look AHEAD will study the effects of the interventions on other factors relating to heart disease, on diabetes control and complications, and on relative costs and quality of life associated with the interventions. Overall, this study will help doctors in the future in advising their patients who have diabetes about losing weight.
About 5,000 men and women in 19 cities around the country will take part in the study. The study will last 9 to 11.5 years: the length of time will depend on when the individual starts the study.
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
- Myocardial Infarction
- Kidney Diseases
- Bone Diseases
- Behavioral: 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.
- Behavioral: Diabetes Support and Education
Participants assigned to diabetes support and education are offered three sessions each year in diabetes management and social support.
- Experimental: Lifestyle Intervention
Participants in the lifestyle intervention arm are offered individual and group sessions designed to help achieve and maintain weight loss.
Intervention: Behavioral: Lifestyle Intervention
- Active Comparator: Diabetes Support and Education
The diabetes support and education arm provides group sessions on diabetes management and social support.
Intervention: Behavioral: Diabetes Support and Education
- Look AHEAD Research Group. Effect of a long-term behavioural weight loss intervention on nephropathy in overweight or obese adults with type 2 diabetes: a secondary analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol. 2014 Oct;2(10):801-9. doi: 10.1016/S2213-8587(14)70156-1. Epub 2014 Aug 10.
- Lipkin EW, Schwartz AV, Anderson AM, Davis C, Johnson KC, Gregg EW, Bray GA, Berkowitz R, Peters AL, Hodges A, Lewis C, Kahn SE; Look AHEAD Research Group. The Look AHEAD Trial: bone loss at 4-year follow-up in type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2822-9. doi: 10.2337/dc14-0762. Epub 2014 Jul 21.
- Look AHEAD Research Group. Impact of intensive lifestyle intervention on depression and health-related quality of life in type 2 diabetes: the Look AHEAD Trial. Diabetes Care. 2014 Jun;37(6):1544-53. doi: 10.2337/dc13-1928.
- Unick JL, Hogan PE, Neiberg RH, Cheskin LJ, Dutton GR, Evans-Hudnall G, Jeffery R, Kitabchi AE, Nelson JA, Pi-Sunyer FX, West DS, Wing RR; Look AHEAD Research Group. Evaluation of early weight loss thresholds for identifying nonresponders to an intensive lifestyle intervention. Obesity (Silver Spring). 2014 Jul;22(7):1608-16. doi: 10.1002/oby.20777. Epub 2014 Apr 28.
- Look AHEAD Research Group. Eight-year weight losses with an intensive lifestyle intervention: the look AHEAD study. Obesity (Silver Spring). 2014 Jan;22(1):5-13. doi: 10.1002/oby.20662.
- McCaffery JM, Papandonatos GD, Huggins GS, Peter I, Erar B, Kahn SE, Knowler WC, Lipkin EW, Kitabchi AE, Wagenknecht LE, Wing RR; Genetic Subgroup of Look AHEAD; Look AHEAD Research Group. Human cardiovascular disease IBC chip-wide association with weight loss and weight regain in the look AHEAD trial. Hum Hered. 2013;75(2-4):160-74. doi: 10.1159/000353181. Epub 2013 Sep 27.
- Look AHEAD Research Group, Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM, Espeland MA, Evans M, Foreyt JP, Ghazarian S, Gregg EW, Harrison B, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montez MG, Murillo A, Nathan DM, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Reboussin D, Regensteiner JG, Rickman AD, Ryan DH, Safford M, Wadden TA, Wagenknecht LE, West DS, Williamson DF, Yanovski SZ. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013 Jul 11;369(2):145-54. doi: 10.1056/NEJMoa1212914. Epub 2013 Jun 24.
- Wing RR, Bond DS, Gendrano IN 3rd, Wadden T, Bahnson J, Lewis CE, Brancati F, Schneider S, Kitabchi AE, Van Dorsten B, Rosen RC; Sexual Dysfunction Subgroup of the Look AHEAD Research Group. Effect of intensive lifestyle intervention on sexual dysfunction in women with type 2 diabetes: results from an ancillary Look AHEAD study. Diabetes Care. 2013 Oct;36(10):2937-44. doi: 10.2337/dc13-0315. Epub 2013 Jun 11.
- Schwenke DC, Foreyt JP, Miller ER 3rd, Reeves RS, Vitolins MZ; Oxidative Stress Subgroup of the Look AHEAD Research Group. Plasma concentrations of trans fatty acids in persons with type 2 diabetes between September 2002 and April 2004. Am J Clin Nutr. 2013 Apr;97(4):862-71. doi: 10.3945/ajcn.112.046508. Epub 2013 Feb 27.
- Unick JL, Beavers D, Bond DS, Clark JM, Jakicic JM, Kitabchi AE, Knowler WC, Wadden TA, Wagenknecht LE, Wing RR; Look AHEAD Research Group. The long-term effectiveness of a lifestyle intervention in severely obese individuals. Am J Med. 2013 Mar;126(3):236-42, 242.e1-2. doi: 10.1016/j.amjmed.2012.10.010. PubMed PMID: 23410564; PubMed Central PMCID: PMC3574274.
- Rubin RR, Peyrot M, Gaussoin SA, Espeland MA, Williamson D, Faulconbridge LF, Wadden TA, Ewing L, Safford M, Evans-Hudnall G, Wing RR, Knowler WC; Look AHEAD Research Group. Four-year analysis of cardiovascular disease risk factors, depression symptoms, and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes. Diabetes Care. 2013 May;36(5):1088-94. doi: 10.2337/dc12-1871. Epub 2013 Jan 28.
- Gregg EW, Chen H, Wagenknecht LE, Clark JM, Delahanty LM, Bantle J, Pownall HJ, Johnson KC, Safford MM, Kitabchi AE, Pi-Sunyer FX, Wing RR, Bertoni AG; Look AHEAD Research Group. Association of an intensive lifestyle intervention with remission of type 2 diabetes. JAMA. 2012 Dec 19;308(23):2489-96. doi: 10.1001/jama.2012.67929.
- Jakicic JM, Egan CM, Fabricatore AN, Gaussoin SA, Glasser SP, Hesson LA, Knowler WC, Lang W, Regensteiner JG, Ribisl PM, Ryan DH; Look AHEAD Research Group. Four-year change in cardiorespiratory fitness and influence on glycemic control in adults with type 2 diabetes in a randomized trial: the Look AHEAD Trial. Diabetes Care. 2013 May;36(5):1297-303. doi: 10.2337/dc12-0712. Epub 2012 Dec 6.
- McCaffery JM, Papandonatos GD, Peter I, Huggins GS, Raynor HA, Delahanty LM, Cheskin LJ, Balasubramanyam A, Wagenknecht LE, Wing RR; Genetic Subgroup of Look AHEAD; Look AHEAD Research Group. Obesity susceptibility loci and dietary intake in the Look AHEAD Trial. Am J Clin Nutr. 2012 Jun;95(6):1477-86. doi: 10.3945/ajcn.111.026955. Epub 2012 Apr 18.
- Rejeski WJ, Ip EH, Bertoni AG, Bray GA, Evans G, Gregg EW, Zhang Q; Look AHEAD Research Group. Lifestyle change and mobility in obese adults with type 2 diabetes. N Engl J Med. 2012 Mar 29;366(13):1209-17. doi: 10.1056/NEJMoa1110294.
- Schwartz AV, Johnson KC, Kahn SE, Shepherd JA, Nevitt MC, Peters AL, Walkup MP, Hodges A, Williams CC, Bray GA; Look AHEAD Research Group. Effect of 1 year of an intentional weight loss intervention on bone mineral density in type 2 diabetes: results from the Look AHEAD randomized trial. J Bone Miner Res. 2012 Mar;27(3):619-27. doi: 10.1002/jbmr.1483.
- Brancati FL, Evans M, Furberg CD, Geller N, Haffner S, Kahn SE, Kaufmann PG, Lewis CE, Nathan DM, Pitt B, Safford MM; Look AHEAD Study Group. Midcourse correction to a clinical trial when the event rate is underestimated: the Look AHEAD (Action for Health in Diabetes) Study. Clin Trials. 2012 Feb;9(1):113-24. doi: 10.1177/1740774511432726.
- Phelan S, Kanaya AM, Subak LL, Hogan PE, Espeland MA, Wing RR, Burgio KL, DiLillo V, Gorin AA, West DS, Brown JS; Look AHEAD Research Group. Weight loss prevents urinary incontinence in women with type 2 diabetes: results from the Look AHEAD trial. J Urol. 2012 Mar;187(3):939-44. doi: 10.1016/j.juro.2011.10.139. Epub 2012 Jan 20.
- Mount DL, Davis C, Kennedy B, Raatz S, Dotson K, Gary-Webb TL, Thomas S, Johnson KC, Espeland MA; Look AHEAD Research Group. Factors influencing enrollment of African Americans in the Look AHEAD trial. Clin Trials. 2012 Feb;9(1):80-9. doi: 10.1177/1740774511427929. Epub 2011 Nov 7.
- Bertoni AG, Wagenknecht LE, Kitzman DW, Marcovina SM, Rushing JT, Espeland MA; Brain Natriuretic Peptide Subgroup of the Look AHEAD Research Group. Impact of the look AHEAD intervention on NT-pro brain natriuretic peptide in overweight and obese adults with diabetes. Obesity (Silver Spring). 2012 Jul;20(7):1511-8. doi: 10.1038/oby.2011.296. Epub 2011 Sep 29.
- Unick JL, Beavers D, Jakicic JM, Kitabchi AE, Knowler WC, Wadden TA, Wing RR; Look AHEAD Research Group. Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes: results from the Look AHEAD trial. Diabetes Care. 2011 Oct;34(10):2152-7. doi: 10.2337/dc11-0874. Epub 2011 Aug 11.
- Wesche-Thobaben JA. The development and description of the comparison group in the Look AHEAD trial. Clin Trials. 2011 Jun;8(3):320-9. doi: 10.1177/1740774511405858.
- Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, Hill JO, Brancati FL, Peters A, Wagenknecht L; Look AHEAD Research Group. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011 Jul;34(7):1481-6. doi: 10.2337/dc10-2415. Epub 2011 May 18.
- Belalcazar LM, Ballantyne CM, Lang W, Haffner SM, Rushing J, Schwenke DC, Pi-Sunyer FX, Tracy RP; Look Action for Health in Diabetes Research Group. Metabolic factors, adipose tissue, and plasminogen activator inhibitor-1 levels in type 2 diabetes: findings from the look AHEAD study. Arterioscler Thromb Vasc Biol. 2011 Jul;31(7):1689-95. doi: 10.1161/ATVBAHA.111.224386. Epub 2011 Apr 21.
- Look AHEAD Research Group. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010 Sep 27;170(17):1566-75.
- Belalcazar LM, Reboussin DM, Haffner SM, Hoogeveen RC, Kriska AM, Schwenke DC, Tracy RP, Pi-Sunyer FX, Ballantyne CM; Look AHEAD Research Group. A 1-year lifestyle intervention for weight loss in individuals with type 2 diabetes reduces high C-reactive protein levels and identifies metabolic predictors of change: from the Look AHEAD (Action for Health in Diabetes) study. Diabetes Care. 2010 Nov;33(11):2297-303. Epub 2010 Aug 3.
- Rubin RR, Gaussoin SA, Peyrot M, DiLillo V, Miller K, Wadden TA, West DS, Wing RR, Knowler WC; Look AHEAD Research Group. Cardiovascular disease risk factors, depression symptoms and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes. Diabetologia. 2010 Aug;53(8):1581-9. doi: 10.1007/s00125-010-1765-1. Epub 2010 Apr 28.
- Jakicic JM, Gregg E, Knowler W, Kelley DE, Lang W, Miller GD, Pi-Sunyer FX, Regensteiner JG, Rejeski WJ, Ridisl P, Walkup MP, Wolf DL. Activity patterns of obese adults with type 2 diabetes in the look AHEAD study. Med Sci Sports Exerc. 2010 Nov;42(11):1995-2005. doi: 10.1249/MSS.0b013e3181e054f0.
- Redmon JB, Bertoni AG, Connelly S, Feeney PA, Glasser SP, Glick H, Greenway F, Hesson LA, Lawlor MS, Montez M, Montgomery B; Look AHEAD Research Group. Effect of the look AHEAD study intervention on medication use and related cost to treat cardiovascular disease risk factors in individuals with type 2 diabetes. Diabetes Care. 2010 Jun;33(6):1153-8. doi: 10.2337/dc09-2090. Epub 2010 Mar 23.
- Belalcazar LM, Reboussin DM, Haffner SM, Reeves RS, Schwenke DC, Hoogeveen RC, Pi-Sunyer FX, Ballantyne CM; Look AHEAD (Action for Health in Diabetes) Obesity, Inflammation, and Thrombosis Research Group. Marine omega-3 fatty acid intake: associations with cardiometabolic risk and response to weight loss intervention in the Look AHEAD (Action for Health in Diabetes) study. Diabetes Care. 2010 Jan;33(1):197-9. Epub 2009 Oct 19.
- Williamson DA, Rejeski J, Lang W, Van Dorsten B, Fabricatore AN, Toledo K; Look AHEAD Research Group. Impact of a weight management program on health-related quality of life in overweight adults with type 2 diabetes. Arch Intern Med. 2009 Jan 26;169(2):163-71.
- Gorin AA, Niemeier HM, Hogan P, Coday M, Davis C, DiLillo VG, Gluck ME, Wadden TA, West DS, Williamson D, Yanovski SZ; Look AHEAD Research Group. Binge eating and weight loss outcomes in overweight and obese individuals with type 2 diabetes: results from the Look AHEAD trial. Arch Gen Psychiatry. 2008 Dec;65(12):1447-55.
- Espeland MA, Regensteiner JG, Jaramillo SA, Gregg E, Knowler WC, Wagenknecht LE, Bahnson J, Haffner S, Hill J, Hiatt WR; Look AHEAD Study Group. Measurement characteristics of the ankle-brachial index: results from the Action for Health in Diabetes study. Vasc Med. 2008 Aug;13(3):225-33.
- Raynor HA, Jeffery RW, Ruggiero AM, Clark JM, Delahanty LM; Look AHEAD (Action for Health in Diabetes) Research Group. Weight loss strategies associated with BMI in overweight adults with type 2 diabetes at entry into the Look AHEAD (Action for Health in Diabetes) trial. Diabetes Care. 2008 Jul;31(7):1299-304. Epub 2008 Mar 28.
- Ribisl PM, Lang W, Jaramillo SA, Jakicic JM, Stewart KJ, Bahnson J, Bright R, Curtis JF, Crow RS, Soberman JE; Look AHEAD Research Group. Exercise capacity and cardiovascular/metabolic characteristics of overweight and obese individuals with type 2 diabetes: the Look AHEAD clinical trial. Diabetes Care. 2007 Oct;30(10):2679-84. Epub 2007 Jul 20.
|Active, not recruiting
|December 2014 (final data collection date for primary outcome measure)
- Type 2 diabetes
- 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
- 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).
- 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.
- 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.
- Amputation of lower limbs as result of non-traumatic causes.
- Any major organ transplant.
|55 Years to 75 Years
|Contact information is only displayed when the study is recruiting subjects
|SHOW, U01DK57136, U01DK57149, U01DK56990, U01DK57177, U01DK57171, U01DK57151, U01DK57182, U01DK57131, U01DK57002, U01DK57078, U01DK57154, U01DK57178, U01DK219, U01DK57008, U01DK57135, U01DK56992
|Mary Evans, Ph.D./Program Officer, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Heart, Lung, and Blood Institute (NHLBI)
- National Institute of Nursing Research (NINR)
- National Center on Minority Health and Health Disparities (NCMHD)
- Office of Research on Women's Health (ORWH)
|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)