Semaglutide and Structured Lifestyle Support to Improve Heart and Blood Vessel Health in Postmenopausal Obese Breast Cancer Survivors Taking Aromatase Inhibitors

NCT07769047 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 3 other identifiers: 25-012266K23HL183845NCI-2026-04536
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage I Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (3)

• Change in PWV between arms (Aim 1)

  Will assess the change in pulse wave velocity (PWV) between arms from baseline to 24 weeks.

  Baseline to 24 weeks

• Change in protein expression between arms (Aim 2a)

  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.

  Baseline to 24 weeks

• Significantly enriched biological pathways and gene sets among DEPs (Aim 2b)

  Will identify biological pathways and gene sets significantly enriched among the differentially expressed proteins (DEPs) between arms.

  Up to 24 weeks

Secondary Outcomes (23)

• Change in AIx between arms (Aim 1)

  Baseline to 24 weeks

• Change in RHI between arms (Aim 1)

  Baseline to 24 weeks

• Change in PWV within arms (Aim 1)

  Baseline to 24 weeks

• Change in AIx within arms (Aim 1)

  Baseline to 24 weeks

• Change in RHI within arms (Aim 1)

  Baseline to 24 weeks

Other Outcomes (1)

• Examine functional significance of semaglutide-induced DEPs through enrichment analysis (Aim 2b)

  Up to 24 weeks

Study Arms (2)

Arm I (LM)

ACTIVE COMPARATOR

Patients receive recommendations for a structured lifestyle intervention over 24 weeks consisting of the following: 1) a low-calorie diet based on their Harris-Benedict predicted resting energy expenditure, reduced by 500 kcal/day; (2) a physical activity goal of ≥ 10,000 steps/day; (3) ≥ 150 minutes per week of moderate-intensity aerobic exercise with resistance training; and (4) limited liquid calorie intake (e.g., sodas, juices, alcohol). Additionally, patients undergo blood sample collection, vascular function testing, and DEXA on study.

Procedure: Biospecimen Collection; Procedure: Dual X-ray Absorptiometry; Other: Functional Assessment; Behavioral: Lifestyle Counseling

Arm II (LM+Sema)

EXPERIMENTAL

Patients receive recommendations for a structured lifestyle intervention over 24 weeks consisting of the following: 1) a low-calorie diet based on their Harris-Benedict predicted resting energy expenditure, reduced by 500 kcal/day; (2) a physical activity goal of ≥ 10,000 steps/day; (3) ≥ 150 minutes per week of moderate-intensity aerobic exercise with resistance training; and (4) limited liquid calorie intake (e.g., sodas, juices, alcohol). Patients also receive semaglutide SC QW for up to 24 weeks in the absence of unacceptable toxicity. Additionally, patients undergo blood sample collection, vascular function testing, and DEXA on study.

Procedure: Biospecimen Collection; Procedure: Dual X-ray Absorptiometry; Other: Functional Assessment; Behavioral: Lifestyle Counseling; Drug: Semaglutide

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm I (LM); Arm II (LM+Sema)

Dual X-ray Absorptiometry PROCEDURE

Undergo DEXA

Also known as: BMD scan, bone mineral density scan, DEXA, DEXA (Bone Density), DEXA Scan, dual energy x-ray absorptiometric scan, Dual Energy X-ray Absorptiometry, Dual X-Ray Absorptometry, DXA, DXA SCAN

Arm I (LM); Arm II (LM+Sema)

Functional Assessment OTHER

Undergo vascular function testing

Arm I (LM); Arm II (LM+Sema)

Lifestyle Counseling BEHAVIORAL

Receive structured lifestyle intervention recommendations

Arm I (LM); Arm II (LM+Sema)

Semaglutide DRUG

Given SC

Also known as: Ozempic, Rybelsus, Wegovy

Arm II (LM+Sema)

Eligibility Criteria

• Age: 46 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• \> 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
• 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)

Sponsors & Collaborators

• Mayo Clinic: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

Specimen Handling; Absorptiometry, Photon; Bone Density; semaglutide

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Radiography; Diagnostic Imaging; Densitometry; Photometry; Chemistry Techniques, Analytical; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Maria Daniela Hurtado Andrade, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

General Clinical Studies Unit

CONTACT

904-953-2255

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2026
• First Posted: August 17, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): July 30, 2031
• Study Completion (Estimated): July 30, 2035
• Last Updated: August 17, 2026

Record last verified: 2026-07

Locations

US (1)