DECODE Heartland: Understanding and Addressing Disparities in Cancer Therapy Induced Inflammation and Associated Endothelial Dysfunction
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
Study locations (2)
University of Illinois Chicago
Chicago, Illinois, 60607
Medical College of Wisconsin
Wauwatosa, Wisconsin, 53226