Clinical trial NCT05223322: Understanding and Addressing Disparities in Cancer Therapy Induced Inflammation and Associated Endothelial Dysfunction
Official title: DECODE Heartland: Understanding and Addressing Disparities in Cancer Therapy Induced Inflammation and Associated Endothelial Dysfunction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: University of Illinois at Chicago
First posted: 2022-02-03
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: T1 (baseline), T2 (18-24 weeks), and T3 (12 months)
Secondary outcomes:
measure: Functional Assessment of Cancer Therapy - General (FACT-B)
timeFrame: T1 (baseline), T2 (18-24 weeks), and T3 (12 months)
measure: The Distress Thermometer
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Perceived Stress Scale
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Hospital Anxiety and Depression Scale
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: The Functional Assessment of Chronic Illness Therapy - Fatigue
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: PROMIS - Social Support
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12 months)
measure: PROMIS - Pain Interference
timeFrame: T1 (baseline), T2 (18-24 weeks), and T3 (12-15 months)
measure: Assess mitochondrial DNA damage
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Cytokine analysis
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Gene Express Profiling
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (115 months)
measure: Endothelial function
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Flow Mediated Dilation
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12 months)
measure: Cardiac function - Echocardiagram
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Cardiac function - Pulse Wave Velocity
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Cognitive Function
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Other outcomes:
measure: DEXA Scan
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Height and Weight
timeFrame: T1 (baseline), T2 (18-24 weeks), and T3 (12-15 months)
measure: Accelerometry
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Physical Activity self report
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Pittsburgh Sleep Quality Index
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Sitting Time Questionnaire
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Handgrip strength
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: Sit to Stand
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
measure: 6 Minute Walk Test
timeFrame: T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Locations:
city: Chicago
country: United States
facility: University of Illinois Chicago
state: Illinois
city: Wauwatosa
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References: