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

Breast Cancer Clinical Trial

— DECODE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05223322
• Other study ID #: PRO00041443
• Status: Recruiting
• Phase: N/A
• Start date: March 1, 2022
• Est. completion date: July 1, 2026

Study information

• Verified date: March 2024
• Source: Medical College of Wisconsin
• Contact: Melinda Stolley, PhD
• Phone: 414-955-7533
• Email: mstolley[@]mcw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: July 1, 2026
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Inflammation

Intervention

Behavioral:
• Taking 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.

Locations

Country	Name	City	State
United States	University of Illinois Chicago	Chicago	Illinois
United States	Medical College of Wisconsin	Wauwatosa	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Medical College of Wisconsin	University of Illinois at Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	DEXA Scan	Body composition: DXA imaging is a 10 minute, noninvasive, technique that provides precise whole-body measurements of fat (total and visceral) and lean mass. Certified DXA technologists will perform and analyze whole body measures using the same machine for each participant at each time point. To ensure reliability and precision, machines are calibrated daily.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Other	Height and Weight	Height and Weight: To calculate BMI, investigators will will assess height (baseline only) using a portable stadiometer and weight using a digital scale with participants wearing light clothes and no shoes. A 0.2 kg discrepancy in weight or a 0.5 cm discrepancy in height in the first two measurements, will result in a third measurement.	T1 (baseline), T2 (18-24 weeks), and T3 (12-15 months)
Other	Accelerometry	Accelerometry. Summary measures of PA levels will be derived from 7-day accelerometer wear data (% time sedentary, % time moderate to vigorous PA, counts per minute). Study team will adopt the common guideline of 10 hours or more of wear time necessary to define a valid day. Investigators will use the Troiano cut points (sedentary, light, moderate, vigorous).	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Other	Physical Activity self report	Godin Leisure Activity Index collects data on mild, moderate, and vigorous activity.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Other	Pittsburgh Sleep Quality Index	This is an effective instrument used to measure the quality and patterns of sleep in adults. It differentiates "poor" from "good" sleep quality by measuring seven areas.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Other	Sitting Time Questionnaire	The STQ is a 5-question self-report survey asking about amount of time spent sedentary.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Other	Handgrip strength	Measured with a Takei handgrip dynamometer. This test of LM function correlates with total body muscle strength73 and mortality74.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Other	Sit to Stand	Number of completed Sit to Stand repetitions performed in 30 secs using a chair with no arms with a height of approximately 43 cm75.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Other	6 Minute Walk Test	Total distance traveled in 6 mins is recorded and used to determine endurance.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
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.	T1 (baseline), T2 (18-24 weeks), and T3 (12 months)
Secondary	Functional Assessment of Cancer Therapy - General (FACT-B)	This survey measures physical, social, emotional, and functional wellbeing and wellness and symptoms associated with breast cancer and its treatments.	T1 (baseline), T2 (18-24 weeks), and T3 (12 months)
Secondary	The Distress Thermometer	This is a simple tool to effectively screen for symptoms of distress.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Secondary	Perceived Stress Scale	This survey is a class stress assessment to help understand how different situations affect feelings and perceived stress, asking about thoughts and feelings.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Secondary	Hospital Anxiety and Depression Scale	This will measure anxiety and depression in a general medical population of patients.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Secondary	The Functional Assessment of Chronic Illness Therapy - Fatigue	Participants will self-report fatigue and its impact upon daily activities and function.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Secondary	PROMIS - Social Support	This survey will assess how much social support each individual has in their personal network.	T1 (baseline), T2 (18-40 weeks), and T3 (12 months)
Secondary	PROMIS - Pain Interference	This instrument will measure the self-reported consequences of pain on relevant aspects of a person's life.	T1 (baseline), T2 (18-24 weeks), and T3 (12-15 months)
Secondary	Assess mitochondrial DNA damage	Mitochondrial DNA damage will be assessed in isolated vessels from biopsies and total peripheral blood mononuclear blood cells (PBMCs) via a well-established PCR protocol. Similarly, a PCR based method is used to quantify levels of cell free mtDNA in plasma samples from study participants.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Secondary	Cytokine analysis	Investigators will utilize Isoplex platform via CodePlex Human Cytokine Storm Panel-8 to quantify a large array of inflammatory cytokines using minimal amounts (<30 ul) of plasma sample.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Secondary	Gene Express Profiling	Transcriptomic expression profiling of PBMC and endothelial cells will be performed utilizing existing infrastructure (Genomic Sciences and Precision Medicine Center at MCW). RNA sequencing will be performed Illumina on NovaSeq sequencer.	T1 (baseline), T2 (18-40 weeks), and T3 (115 months)
Secondary	Endothelial function	Microvascular function from gluteal and surgical fat biopsies will be used to test the direct effect of clinically used chemotherapy on peripheral microvascular function (as surrogate for coronary microvessels). Investigators propose to perform studies before, after the chemotherapy regimen, and at 12 months follow up. Study team evaluate microvascular dilator capacity, both endothelial and smooth muscle mediated, and quantify levels of vasodilators (NO and H2O2) via fluorescent probes.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Secondary	Flow Mediated Dilation	Flow mediated dilation of the brachial artery (large conduit vessels) will be assessed using ultrasound in a noninvasive manner.	T1 (baseline), T2 (18-40 weeks), and T3 (12 months)
Secondary	Cardiac function - Echocardiagram	Echocardiograms: Aortic diameter, cardiac output, stroke volume, heart rate, end diastolic, and end systolic volume will be assessed at rest using two-dimensional echocardiography. With subjects in the left lateral position, measurements will be obtained using the two (Parasternal and Short Axis) and four-chamber view.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Secondary	Cardiac function - Pulse Wave Velocity	Pulse Wave Velocity: A non-invasive technique will be used to measure arterial stiffness (pulse wave velocity and central pressures). Briefly, investigators will record waveforms at the carotid and femoral arteries using tonometry and a partially inflated pressure cuff placed over the upper arm and thigh. The distance between sites will be determined using a tape measure.	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)
Secondary	Cognitive Function	PROMIS - Cognitive Function Short Form: This is a short six-item sub-set scale of the full PROMIS Cognitive Function item bank that assesses patient-perceived cognitive deficits	T1 (baseline), T2 (18-40 weeks), and T3 (12-15 months)