Gene x Behavior Interaction in the Look AHEAD Study

NCT ID: NCT01270763

Last Updated: 2015-03-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 4108 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2015-03-31

Brief Summary

The interplay of genetic and behavioral factors is critical to understanding obesity. Behavioral weight loss intervention has emerged as a key strategy in combating obesity. However, individuals differ in their degree of success in these programs and genetic factors are known to play a role. In this application, the investigators propose to identify specific genes that predict individual differences in weight loss and high density lipoprotein cholesterol in response to behavioral intervention to help identify individuals that struggle with weight loss and cholesterol despite behavioral efforts.

Detailed Description

The interplay of genetic and behavioral factors is critical to understanding obesity. Obesity is a major public health problem, with millions of Americans suffering from weight-related health complications, including Type 2 diabetes, coronary heart disease, hypertension, and osteoarthritis. Behavioral weight loss intervention has emerged as a key strategy in combating obesity and the associated health consequences. However, individuals differ in their degree of success in these programs even if they make the recommended behavioral changes and genetic factors are known to play a role. In this application, the investigators propose to identify specific genes that predict individual differences in weight loss in response to behavioral intervention to help identify individuals who struggle with weight loss despite behavioral efforts. Specifically, the investigators will determine whether obesity genes interact with lifestyle intervention in predicting weight loss at year 1 of the Look AHEAD trial, an NIH-funded, multi-center randomized controlled trial with the primary goal of determining whether weight loss achieved through an intensive lifestyle intervention can reduce cardiovascular morbidity and mortality among persons with type 2 diabetes. At year 1, participants assigned to Intensive Lifestyle Intervention (ILI), focusing on changes in diet and physical activity, lost an average of 8.6% of their weight (N = 2,496; 97.1% follow-up) relative to losses of 0.7% among individuals assigned to the Diabetes Support and Education (DSE) group (N= 2,463, 95.7% follow-up), who received diabetes support and education groups alone. Consent for genetic analyses was provided by 3,759 participants. Genotype data from the IBC chip, a genotyping platform including 50,000 single nucleotide polymorphisms (SNPs) from ~2,600 genes relevant to cardiovascular disease, lipid metabolism, diabetes and obesity, will allow us to test the central hypothesis that genes that predispose to obesity interact with lifestyle treatment to influence weight loss following intensive lifestyle intervention. The investigators will also determine whether genes related to high density lipoprotein (HDL) cholesterol predict the degree of improvement in HDL in response to the behavioral intervention. The investigators conduct these aims with the explicit goal of bringing together a team with expertise in behavioral research, genetic epidemiology and molecular biology to create transdisciplinary researchers who are able to bridge across the disciplines and identify key gene x behavior interactions in the context of the Look AHEAD trial.

Conditions

Obesity; Type 2 Diabetes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

The Look AHEAD Study

The Look AHEAD Study includes intensive lifestyle intervention treatment, focusing on caloric intake and physical activity, and a treatment arm focused on diabetes support and education.

Intensive lifestyle intervention

Intervention Type: BEHAVIORAL

Lifestyle intervention focused on weight loss through diet and physical activity

Diabetes support and education

Intervention Type: BEHAVIORAL

Behavioral intervention focused on diabetes support and education

Interventions

Intensive lifestyle intervention

Lifestyle intervention focused on weight loss through diet and physical activity

Intervention Type: BEHAVIORAL

Diabetes support and education

Behavioral intervention focused on diabetes support and education

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Enrollment in the Look AHEAD Study, genetic consent

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tufts Medical Center

OTHER

Sponsor Role: collaborator

Brown University

OTHER

Sponsor Role: collaborator

The Miriam Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jeanne McCaffery

Senior Research Scientist/Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeanne McCaffery, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The Miriam Hospital

Rena Wing, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The Miriam Hospital

Locations

The Miriam Hospital

Providence, Rhode Island, United States

Countries

United States

References

Look AHEAD Research Group. Prospective Association of GLUL rs10911021 With Cardiovascular Morbidity and Mortality Among Individuals With Type 2 Diabetes: The Look AHEAD Study. Diabetes. 2016 Jan;65(1):297-302. doi: 10.2337/db15-0890. Epub 2015 Sep 22.

Reference Type: DERIVED

PMID: 26395743 (View on PubMed)

Look AHEAD Research Group. Prospective association of a genetic risk score and lifestyle intervention with cardiovascular morbidity and mortality among individuals with type 2 diabetes: the Look AHEAD randomised controlled trial. Diabetologia. 2015 Aug;58(8):1803-13. doi: 10.1007/s00125-015-3610-z. Epub 2015 May 14.

Reference Type: DERIVED

PMID: 25972230 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24081232 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22513296 (View on PubMed)

Other Identifiers

GxB in Look AHEAD

Identifier Type: -

Identifier Source: org_study_id