Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
Conditions
Brief summary
This phase IV trial studies whether adding semaglutide to structured lifestyle support improves heart and blood vessel health in postmenopausal obese breast cancer survivors (BCS) who are taking an aromatase inhibitor. In postmenopausal BCS who are taking an aromatase inhibitor, obesity raises the risk of heart and blood vessel problems. Semaglutide is a medicine approved by the United States Food and Drug Administration for weight loss and for lowering the risk of heart events in people with heart disease. The structured lifestyle support in this trial includes counseling on nutrition and physical activity which provides specific recommendations for individuals to follow.
Interventions
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREDual X-ray Absorptiometry
Undergo DEXA
Undergo vascular function testing
BEHAVIORALLifestyle Counseling
Receive structured lifestyle intervention recommendations
DRUGSemaglutide
Given SC
Sponsors
Mayo Clinic
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Masking description
While participants and clinicians cannot be blinded due to the nature of the intervention, outcome assessors, laboratory personnel, and data analysts will remain blinded through use of coded identifiers and barcoded samples.
Eligibility
Sex/Gender
FEMALE
Age
46 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Breast cancer diagnosed after menopause (menopause defined as the natural/spontaneous cessation of menses for at least 12 months) * Breast cancer (BC) diagnosed within the past five years * BC stage 1, 2, or 3 * Aged 46-55 years * Body mass index (BMI) ≥ 30 kg/m\^² * Current use of an aromatase inhibitor * Ability to participate in all portions of the study, including willingness to self-inject
Exclusion criteria
* \> 5% change in weight during the 3 months prior to screening and/or weight fluctuation of ≥ 20 pounds within the past 6 months (self-report) * Early menopause (menopause occurring before age 46) * History of established cardiovascular disease, including coronary atherosclerosis, ischemic heart disease, peripheral vascular disease, or stroke * Statin use * 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk \> 7.5% * History of smoking * History of type 1 or type 2 diabetes * Family history of premature cardiovascular disease in a first-degree relative (before 45 years old in male relatives and before 55 years old in female relatives) * Use of chemotherapy, radiation therapy, or immunotherapy for breast cancer treatment * Impaired renal function \[glomerular filtration rate (GFR) ≤ 30 ml/min/1.73 m\^²\] * Thyroid-stimulating hormone (TSH) ≥ 7 with low free thyroxine (T4) * Hemoglobin \< 11 mg/dL * Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignancy, or uncontrolled psychiatric disease * Other anti-obesity medication used within the past 3 months * Prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty performed \> 1 year before screening) * Past or intended endoscopic and/or device-based therapy or removal within the last six months * Current or recent (within 3 months) use of medications that may cause weight gain, including tricyclic antidepressants, atypical antipsychotics, and mood stabilizers * Current or recent use (within 3 months) of systemic glucocorticoid therapy for over 2 weeks * Contraindications to glucagon-like peptide 1 (GLP-1) receptor agonist therapy * Currently enrolled in another clinical study involving an investigational product or participated in one and received treatment (active or placebo) in the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in protein expression between arms (Aim 2a) | Baseline to 24 weeks | Will assess the change in protein expression from baseline to 24 weeks between arms. The raw protein concentrations for all samples will be reported in Normalized Protein eXpression (NPX) values, as obtained from the OLINK platform . A log2 scale transformation will be applied to the NPX values to stabilize variance across samples and allow data to be comparable. |
| Significantly enriched biological pathways and gene sets among DEPs (Aim 2b) | Up to 24 weeks | Will identify biological pathways and gene sets significantly enriched among the differentially expressed proteins (DEPs) between arms. |
| Change in PWV between arms (Aim 1) | Baseline to 24 weeks | Will assess the change in pulse wave velocity (PWV) between arms from baseline to 24 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in PWV within arms (Aim 1) | Baseline to 24 weeks | Will assess the change in pulse wave velocity (PWV) from baseline to 24 weeks within each arm. |
| Change in AIx within arms (Aim 1) | Baseline to 24 weeks | Will assess the change in AIx from baseline to 24 weeks within each arm. |
| Change in RHI within arms (Aim 1) | Baseline to 24 weeks | Will assess the change in RHI from baseline to 24 weeks within each arm. |
| Change in body weight between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in body weight from baseline to 24 weeks between arms. |
| Change in fat mass between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in total fat mass and visceral fat mass from baseline to 24 weeks between arms. |
| Change in waist and hip circumference between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in waist and hip circumference from baseline to 24 weeks between arms. |
| Change in blood pressure between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in systolic and/or diastolic blood pressure from baseline to 24 weeks between arms. |
| Change in total cholesterol between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in total cholesterol from baseline to 24 weeks between arms. |
| Change in LDL-cholesterol between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in LDL-cholesterol from baseline to 24 weeks between arms. |
| Change in HDL-cholesterol between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in HDL-cholesterol from baseline to 24 weeks between arms. |
| Change in triglycerides between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in triglycerides from baseline to 24 weeks between arms. |
| Change in fasting glucose parameters between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in fasting glucose from baseline to 24 weeks between arms. |
| Change in HbA1c between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in HbA1c from baseline to 24 weeks between arms. |
| Change in hs-CRP between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in change in high-sensitivity (hs) C-reactive protein (CRP) (hs-CRP) from baseline to 24 weeks between arms. |
| Change in protein expression within arms (Aim 2a) | Baseline to 24 weeks | Will assess the change in protein expression from baseline to 24 weeks within each arm. |
| Difference in protein expression between arms at baseline (Aim 2a) | At baseline | Will assess the difference in protein expression at baseline between arms. |
| Difference in protein expression between arms at 24 weeks (Aim 2a) | At 24 weeks | Will assess the difference in protein expression at 24 weeks between arms. |
| Overlap of change in protein expression within arms (Aim 2a) | At baseline and 24 weeks | Will assess overlap between the two arms in change in protein expression within each arm at baseline and at 24 weeks. |
| Key hub proteins as central regulators in semaglutide-mediated effects (Aim 2b) | Up to 24 weeks | Will identify key hub proteins that may serve as central regulators in semaglutide-mediated effects. |
| Overlap of DEPs and established cardiovascular risk biomarkers (Aim 2b) | Up to 24 weeks | Will evaluate the overlap between DEPs and established cardiovascular risk biomarkers. |
| Network connectivity between DEPs and known molecular pathways (Aim 2b) | Up to 24 weeks | Will assess network connectivity between DEPs and known molecular pathways relevant to metabolic and vascular function. |
| Change in AIx between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in augmentation index (AIx) from baseline to 24 weeks between arms. |
| Change in RHI between arms (Aim 1) | Baseline to 24 weeks | Will assess the difference in reactive hyperemic index (RHI)from baseline to 24 weeks between arms. |
Countries
United States
Contacts
CONTACTClinical Trials Referral Office
CONTACTGeneral Clinical Studies Unit
PRINCIPAL_INVESTIGATORMaria Daniela Hurtado Andrade, MD, PhD
Mayo Clinic
Outcome results
None listed