NCT07769047 - Semaglutide and Structured Lifestyle Support to Improve Heart and Blood Vessel Health in Postmenopausal Obese Breast Cancer Survivors Taking Aromatase Inhibitors | Crick

Eligibility

Sex: FEMALEMin age: 46 YearsMax age: 55 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in PWV between arms (Aim 1)

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

Time frame: 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.

Time frame: 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.

Time frame: Up to 24 weeks

Secondary Outcomes

Change in AIx between arms (Aim 1)

Will assess the difference in augmentation index (AIx) from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in RHI between arms (Aim 1)

Will assess the difference in reactive hyperemic index (RHI)from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in PWV within arms (Aim 1)

Will assess the change in pulse wave velocity (PWV) from baseline to 24 weeks within each arm.

Time frame: Baseline to 24 weeks

Change in AIx within arms (Aim 1)

Will assess the change in AIx from baseline to 24 weeks within each arm.

Time frame: Baseline to 24 weeks

Change in RHI within arms (Aim 1)

Will assess the change in RHI from baseline to 24 weeks within each arm.

Time frame: Baseline to 24 weeks

Change in body weight between arms (Aim 1)

Will assess the difference in change in body weight from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in fat mass between arms (Aim 1)

Will assess the difference in change in total fat mass and visceral fat mass from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in waist and hip circumference between arms (Aim 1)

Will assess the difference in change in waist and hip circumference from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in blood pressure between arms (Aim 1)

Will assess the difference in change in systolic and/or diastolic blood pressure from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in total cholesterol between arms (Aim 1)

Will assess the difference in change in total cholesterol from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in LDL-cholesterol between arms (Aim 1)

Will assess the difference in change in LDL-cholesterol from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in HDL-cholesterol between arms (Aim 1)

Will assess the difference in change in HDL-cholesterol from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in triglycerides between arms (Aim 1)

Will assess the difference in change in triglycerides from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in fasting glucose parameters between arms (Aim 1)

Will assess the difference in change in fasting glucose from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in HbA1c between arms (Aim 1)

Will assess the difference in change in HbA1c from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in hs-CRP between arms (Aim 1)

Will assess the difference in change in high-sensitivity (hs) C-reactive protein (CRP) (hs-CRP) from baseline to 24 weeks between arms.

Time frame: Baseline to 24 weeks

Change in protein expression within arms (Aim 2a)

Will assess the change in protein expression from baseline to 24 weeks within each arm.

Time frame: Baseline to 24 weeks

Difference in protein expression between arms at baseline (Aim 2a)

Will assess the difference in protein expression at baseline between arms.

Time frame: At baseline

Difference in protein expression between arms at 24 weeks (Aim 2a)

Will assess the difference in protein expression at 24 weeks between arms.

Time frame: At 24 weeks

Overlap of change in protein expression within arms (Aim 2a)

Will assess overlap between the two arms in change in protein expression within each arm at baseline and at 24 weeks.

Time frame: At baseline and 24 weeks

Key hub proteins as central regulators in semaglutide-mediated effects (Aim 2b)

Will identify key hub proteins that may serve as central regulators in semaglutide-mediated effects.

Time frame: Up to 24 weeks

Network connectivity between DEPs and known molecular pathways (Aim 2b)

Will assess network connectivity between DEPs and known molecular pathways relevant to metabolic and vascular function.

Time frame: Up to 24 weeks

Overlap of DEPs and established cardiovascular risk biomarkers (Aim 2b)

Will evaluate the overlap between DEPs and established cardiovascular risk biomarkers.

Time frame: Up to 24 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts