Clinical trial NCT01270763: Gene x Behavior Interaction in the Look AHEAD Study
Official title: Gene x Behavior Interaction in the Look AHEAD Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Type 2 Diabetes
Keywords: Obesity
physical fitness
cholesterol levels
genetics
weight loss
Lead sponsor: The Miriam Hospital
Sponsor class: OTHER
Collaborators: name: Tufts Medical Center
name: Brown University
First posted: 2011-01-05
Enrollment: 4108
Sex: ALL
Minimum age (years): 45
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 5,145 individuals who are overweight or obese, have type 2 diabetes and are enrolled in the Look AHEAD Study

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.

Eligibility criteria: Inclusion Criteria:

* Enrollment in the Look AHEAD Study, genetic consent

Primary outcomes:
measure: Body weight
timeFrame: 4 years
measure: High density lipoprotein cholesterol
timeFrame: 4 years
Secondary outcomes:
measure: Dietary intake
timeFrame: 4 years
measure: Physical activity/fitness
timeFrame: 4 years
Other outcomes:
Locations:
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
Study officials:
affiliation: The Miriam Hospital
name: Jeanne McCaffery, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Miriam Hospital
name: Rena Wing, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.