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DECODE Heartland: Understanding and Addressing Disparities in Cancer Therapy Induced Inflammation and Associated Endothelial Dysfunction

NCT ID: NCT05223322Sponsor: Medical College of WisconsinLast updated: 2025-05-02

Summary

Very little is understood about the off-target vascular mechanisms of anti-cancer drug toxicity and the impact of exercise on these changes. Much of what has been learned about molecular pathways regulating vascular endothelial function has been established by logical expansion of knowledge obtained through experimental studies (e.g., discovery of endothelium-derived relaxing factor/nitric oxide). Within the last 10 years technological advancements of -omics approaches, such as RNA-sequencing and shotgun proteomics, have dramatically reduced the cost and technical challenge of accessing these tools for discovery-based research. Investigators are now able to obtain unbiased datasets showing changes in transcript or protein expression within complex samples. With cost and accessibility of sequencing is no longer being substantial bottleneck, one of major challenges researchers now face is determining how to meaningfully interpret profiles from large datasets. The extensive characterization of molecular pathways impacting inflammatory responses, endothelial function and angiogenesis, the pathway and network analysis tools will be an asset for identification molecular pathways relevant to alterations in microvascular endothelial function. The investigators preliminary studies on only a small number of samples highlights this potential of the proposed approach to lead to identify personalized medicine-based profiles that will predict patients are likely to develop microvascular endothelial dysfunction from CTx.

Arms & interventions

  • BehavioralTaking Charge during Treatment (TCT) Intervention

    CT is a 16-20week intervention that promotes adoption of the ACSM exercise guidelines for cancer survivors during treatment, including regular moderate to vigorous physical activity (150 minutes per week of moderate activity or 75 minutes per week of vigorous activity) and a minimum of twice weekly resistance training (RT) minutes during CTx and after. Program components include (1) a binder of information, (2) weekly coaching, (3) 2-4x weekly text messaging and (4) exercise supplies. The TCT program is grounded in Social Cognitive Theory.

Outcome measures

Primary

  • Maximal Exercise: Maximal oxygen consumption will be evaluated using cycle ergometry or treadmill to exhaustion as described in the Integrative Physiology Laboratory at each testing visit.

    Investigators will use a graded protocol, starting at 50 watts followed by 30 watt increments every 2 minutes. Subjects will be connected to a breath-by-breath metabolic system (Cosmed, Italy) for measurement of VO2peak. A maximal effort will be defined as fulfillment of three of the following criteria: 1) A plateau in VO2 with an increase in work rate defined as an increase in VO2 of less than 50 ml/min; 2) A maximal HR within 10 beats of predicted maximal heart rate; 3) A respiratory exchange ratio of greater than 1.15; 4) No increase in heart rate with an increase in work rate (less than 3 beats); or 5) A rating of perceived exertion of 18 or greater on the Borg scale. These criteria are according to and consistent with the AHA exercise testing guidelines and performed regularly in Dr. Phillips' and Dr. Durand's laboratory groups59, 62-66.

    Time frame: T1 (baseline), T2 (18-24 weeks), and T3 (12 months)

Secondary

  • Functional Assessment of Cancer Therapy - General (FACT-B)

    Time frame: T1 (baseline), T2 (18-24 weeks), and T3 (12 months)

  • The Distress Thermometer

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)

  • Perceived Stress Scale

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)

  • Hospital Anxiety and Depression Scale

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)

  • The Functional Assessment of Chronic Illness Therapy - Fatigue

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)

  • PROMIS - Social Support

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12 months)

  • PROMIS - Pain Interference

    Time frame: T1 (baseline), T2 (18-24 weeks), and T3 (12-15 months)

  • Assess mitochondrial DNA damage

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)

  • Cytokine analysis

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)

  • Gene Express Profiling

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (115 months)

  • Endothelial function

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)

  • Flow Mediated Dilation

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12 months)

  • Cardiac function - Echocardiagram

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)

  • Cardiac function - Pulse Wave Velocity

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)

  • Cognitive Function

    Time frame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)

Eligibility criteria

Sex: FemaleAge: 18 Years to 100 YearsHealthy volunteers: No
Inclusion Criteria: * Adult (≥ 18 years) assigned female sex at birth * Diagnosed with invasive non-metastatic breast cancer * Receiving neo-adjuvant CTx (or adjuvant CTx and undergoing breast conserving surgery) that includes anthracyclines (such as DOX) and/or targeted anti-Her2 therapy * Able to safely participate in moderate exercise and strength training based on MD approval * Willing to complete all study activities * Self-identifies as Black/African American or non-Hispanic White Exclusion Criteria: * Unintentional weight loss \> 10% in the past 6 months * Current pregnant and lactating patients. Must have completed lactation prior to study start * Metastatic disease * Diagnosed cardiovascular disease as evidenced by cardiomyopathy (reduced regional or global LV contractility), diastolic dysfunction grade 2 or above, symptomatic coronary - artery disease, ejection fraction below 50% * History of prior chemotherapy or targeted H2N Treatment received less than 3 years ago * Non-English speaking

Study locations (2)

University of Illinois Chicago

Chicago, Illinois, 60607

Recruiting
Shane Phillips · Contact

Medical College of Wisconsin

Wauwatosa, Wisconsin, 53226

Recruiting
Melinda Stolley · Contact