Reach for Health Study: Obesity-related Mechanisms and Mortality in Breast Cancer Survivors

Study Overview
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Brief Summary
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This objective of this randomized controlled trial is to conduct a 2x2 test of a lifestyle intervention and metformin (a drug used to treat diabetes) to investigate how these treatments, alone or in combination, affect biomarkers associated with breast cancer survival. The Reach for Health Study will enroll 340 overweight/obese, postmenopausal breast cancer survivors. After completing the screening process and baseline measures, participants will be randomized in equal numbers to: (1) placebo, (2) metformin, (3) lifestyle intervention and placebo, or (4) lifestyle intervention and metformin. The intervention was powered on the main effects and the planned analyses are to compare: Metformin to Placebo and a separate comparison of Lifestyle intervention to control. The interventions will last for 6 months. Concentrations of circulating biomarkers will be assessed at baseline and 6 months.

Official Title
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Obesity-related Mechanisms and Mortality in Breast Cancer Survivors

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo
* Behavioral: Lifestyle intervention
* Behavioral: Standard printed dietary guidelines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI at least 25.0 kg/m2 Diagnosed with Stage I, II, or III breast cancer within past 5 years Treatment with total mastectomy or breast-sparing surgical removal of cancer with clear macroscopic margins, and axillary dissection, followed by adjuvant breast radiation Not scheduled for or currently undergoing chemotherapy Accessible geographically and by telephone Able to communicate dietary and physical activity data via telephone If taking statins, tamoxifen, or aromatase inhibitors; able and willing to remain on treatment for 6-month study period Post-menopausal at diagnosis Exclusion Criteria: Preliminary bloodwork outside of specified ranges Evidence of renal insufficiency, liver disease, or congestive heart failure Currently taking corticosteroid pills or steroid hormone therapy (including vaginal estrogen creams) Recent initiation (< 3 months ago) of thiazides or β-blockers Taking insulin or other antidiabetic drug Other primary or recurrent invasive cancer in past 10 years Unable to commit to study requirements
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Main effects of the factorial design were the planned primary analysis and what the study was powered on.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin + lifestyle intervention<br> | Drug: Metformin<br>* Week 1: 500 mg at dinner time Weeks 2-4: 1000 mg at dinner time Weeks 5+: 500 mg in morning; 1000 mg at dinner time<br>Behavioral: Lifestyle intervention<br>* Telephone-based lifestyle intervention (dietary change and physical activity) for weight loss.<br>|
| Active Comparator: Placebo + lifestyle intervention<br> | Drug: Placebo<br>* Week 1: 1 pill at dinner time Weeks 2-4: 2 pills at dinner time Weeks 5+: 1 pill in morning; 2 pills at dinner time<br>* Other names: Sugar pill;Behavioral: Lifestyle intervention<br>* Telephone-based lifestyle intervention (dietary change and physical activity) for weight loss.<br>|
| Active Comparator: Metformin + standard dietary guidelines<br> | Drug: Metformin<br>* Week 1: 500 mg at dinner time Weeks 2-4: 1000 mg at dinner time Weeks 5+: 500 mg in morning; 1000 mg at dinner time<br>Behavioral: Standard printed dietary guidelines<br>* Set of standard health education materials provided to participants at single time point (immediately after randomization)<br>|
| Placebo Comparator: Placebo + standard dietary guidelines<br> | Drug: Placebo<br>* Week 1: 1 pill at dinner time Weeks 2-4: 2 pills at dinner time Weeks 5+: 1 pill in morning; 2 pills at dinner time<br>* Other names: Sugar pill;Behavioral: Standard printed dietary guidelines<br>* Set of standard health education materials provided to participants at single time point (immediately after randomization)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin | Insulin measured as percent change from baseline | change from baseline to 6 months | 
| Glucose | Glucose measured as percent change from baseline | change from baseline to 6 months | 
| C-reactive Protein | C-reactive protein measured as percent change from baseline | change from baseline to 6 months | 
| Bioavailable Testosterone | Bioavailable testosterone measured as percent change from baseline | change from baseline to 6 months | 
| Serum Hormone Binding Globulin | Serum hormone binding globulin measured as percent change from baseline | change from baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Survival, Weight loss, Metformin, Biological markers