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

NCT05223322 | Recruiting DMC

• 1 other identifier: PRO00041443
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (15)

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

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

• The Distress Thermometer

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

• Perceived Stress Scale

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

• Hospital Anxiety and Depression Scale

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

• The Functional Assessment of Chronic Illness Therapy - Fatigue

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

Other Outcomes (9)

• DEXA Scan

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

• Height and Weight

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

• Accelerometry

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

Study Arms (2)

Taking Charge during Treatment (TCT) Intervention

ACTIVE COMPARATOR

Taking Charge during Treatment (TCT) Intervention. TCT 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. Participants will receive "Take Charge" program binder, 2-4 x weekly text messaging, activity tracker and resistance bands.

Behavioral: Taking Charge during Treatment (TCT) Intervention

Control Group

NO INTERVENTION

To ensure scientific rigor allowing us to test causal pathways associated with exercise, women will be randomized to the TCT intervention or control group arm. The control group will not receive the TCT intervention The investigators experience teaches us that to increase the likelihood of retaining control group participants, the investigators must offer some resources. Thus, the investigators will provide the control group with a one-page summary of the American College of Sports Medicine exercise recommendations, and the "Take Charge" program binder at the completion of the study. Participants will also receive resistance bands and activity tracker at the end of the study. 95 The investigators will also send weekly text messages with supportive content not related to exercise or lifestyle (i.e., a riddle, "take a moment to smile today," a picture of a baby animal).

Interventions

Taking Charge during Treatment (TCT) Intervention BEHAVIORAL

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.

Taking Charge during Treatment (TCT) Intervention

Eligibility Criteria

• Age: 18 Years - 100 Years
• Gender Eligibility Details: Females currently diagnosed with Breast Cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• University of Illinois at Chicago: collaborator

Study Sites (2)

University of Illinois Chicago

Chicago, Illinois, 60607, United States

RECRUITING

Medical College of Wisconsin

Wauwatosa, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Thrombin Time; Methods

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Blood Coagulation Tests; Hematologic Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Central Study Contacts

Melinda Stolley, PhD

CONTACT

414-955-7533; mstolley@mcw.edu

Courtney Jankowski, MPH

CONTACT

(414) 955-8325; cjankowski@mcw.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Following baseline data collection, participants will be randomized into one of two study arms: intervention (exercise) and control (usual care). The investigators have three strata in this study: 1) race/ethnicity (NHW or Bl/AA), 2) anti-cancer therapy (ANTs, anti-Her2 treatments, or both), and 3) comorbidity profile (low vs. high). (High comorbidity level is defined as \>3 comorbidities that include hypertension, diabetes, hyperlipidemia, BMI 50+, renal failure, liver failure. It is possible there may be other comorbidities that may be identified based on physician feedback and patient approval). The investigators will employ blocked randomization within each site (MCW and UIC) that have their own stratified randomization sequence. Each patient will be randomized to a treatment arm (usual care or exercise) via MCW's OnCore Clinical Trials Management System at the MCW Clinical Trials Office.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: February 3, 2022
• Study Start: March 1, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 2, 2025

Record last verified: 2025-04

Locations

US (2)