The primary goal of this project, co-led by Jeffrey Meyerhardt, MD, MPH, and Jennifer Ligibel, MD, is to examine whether a behavioral intervention aimed at increasing physical activity and metformin, alone or in combination, can reduce the levels of fasting insulin in colorectal and breast cancer survivors.
The specific aims are:
- Determine whether supervised exercise training alone and metformin, either alone or in combination, can decrease fasting insulin level from baseline to 6 months in patients who completed standard therapy for stage I – III colorectal and breast cancer.
- Compare changes in other insulin-related biomarkers, including C-peptide, insulin-like growth factor (IGF)-1, IGF binding protein (IGFGB)-3, adiponectin and leptin by treatment arm.
- Explore for an interaction effect in addition to an additive effect of exercise and metformin in reducing fasting insulin level over the 6 month intervention.
- Compare changes in body mass index by treatment arm as well as self-directed change in diet quality by treatment arm.
- Compare changes in pro-inflammatory markers potentially related to insulin resistance (including IL-1b, IL-6, IL-10, TNF-α, C-reactive protein) by treatment arm.
- Determine whether the theoretical constructs of the theory of planned behavior predict change in exercise behavior in colorectal cancer [and breast cancer] survivors.
Observational evidence suggests that factors related to energy balance, including exercise, body weight and diet, may be related not only to the risk of developing colorectal cancer, but also to prognosis in patients who develop the disease. Several studies have demonstrated that colon cancer risk and recurrence rates are elevated in individuals with higher circulating levels of insulin or C-peptide as well as in individuals with higher levels of insulin-like growth factor (IGF)-1 or lower levels of IGF binding protein (IGFBP)-3. However, there are no data testing strategies to lower levels of insulin or related hormones in colorectal and breast cancer survivors. Two strategies that have strong scientific rationale to impact the insulin-related pathways are exercise intervention and metformin. This project will explore these strategies through a multi-site clinical trial.