Clinical trial NCT03776149: Cardiovascular Function in Cancer Survivors
Official title: Therapeutic Role of Dietary Nitrates on Cardiovascular Function in Cancer Survivors Treated With Anthracycline Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cancer Survivor With History of Anthracycline Chemotherapy
Lead sponsor: Kansas State University
Sponsor class: OTHER
First posted: 2018-12-14
Enrollment: 13
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This study utilizes a 7-day randomized, double-blind, placebo-controlled crossover study design, in which individuals are initially supplemented with a nitrate-rich supplement in the form of a specifically formulated beetroot juice, or nitrate-poor placebo. Individuals will then entered a 7-day washout period before entering the opposing arm of the study.
Primary purpose: SUPPORTIVE_CARE

Brief summary: The aim of the current project is to understand the effect of dietary nitrates (via beet-root juice), on its ability to improve parameters of cardiovascular health in cancer survivors with a history of anthracycline chemotherapy.

Detailed description: Cancer remains one of the leading causes of death in modern society, but due in part to increasing rates of detection coupled with advanced therapies, of the ≈230,000 people newly diagnosed with breast cancer each year, approximately 90% are expected to live beyond 5 years. Despite the trend in improved cancer-related mortality, breast cancer survivors are at a significantly increased risk for cardiovascular disease (CVD) morbidity and mortality. As such the American Heart Association has recently highlighted the immediate need to evaluate changes in cardiovascular health and function in the early stages of cancer treatment.

The mechanisms of adjuvant therapies on cardiovascular function may be the result of increased generation of reactive oxygen species (ROS) and altered redox status, specifically the balance between nitric oxide and superoxide. As such, nitrate supplementation has been shown to attenuate Doxorubicin (chemotherapy drug)-induced ventricular function in animal models. These data implicate dietary nitrates as one potential therapeutic intervention that could be used to improve cardiovascular health in cancer survivors.

Beetroot juice (BRJ) is a nutritional supplement that has been studied to examine potential effects of dietary nitrates affecting vasodilation. The increased nitrate levels have been implicated in helping increase nitric oxide bioavailability, which have been shown to improve cardiovascular function in older adults and those with known cardiovascular disease. The question, however, of whether or not BRJ will enhance cardiovascular function in breast cancer survivors is yet to be determined.

The primary aim of the current investigation is to test the hypothesis that dietary nitrate supplementation, via beet-root juice, improves parameters of cardiovascular health in cancer survivors with a history of anthracycline chemotherapy treatment.

Eligibility criteria: Inclusion Criteria:

* cancer survivors (at least 1 year post treatment)
* Prior administration of anthracycline chemotherapy
* partial/complete remission

Exclusion Criteria:

* Unable to provide informed consent
* Kidney disease
* High risk of kidney stones
* Diagnosed hemochromatosis
* Pregnant, breast feeding, or planning to become pregnant
* Non-English speaking

Primary outcomes:
measure: Change in Left ventricular function
timeFrame: The change between day 1 and day 21
Secondary outcomes:
measure: Change in Vascular function
timeFrame: The change between day 1 and day 21
measure: Change in Blood pressure
timeFrame: The change between day 1 and day 21
Other outcomes:
Locations:
city: Manhattan
country: United States
facility: Kansas State University - Clinical Integrative Physiology Laboratory
state: Kansas
Study officials:
References:
citation: Patnaik JL, Byers T, DiGuiseppi C, Dabelea D, Denberg TD. Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study. Breast Cancer Res. 2011 Jun 20;13(3):R64. doi: 10.1186/bcr2901.
citation: Mulrooney DA, Blaes AH, Duprez D. Vascular injury in cancer survivors. J Cardiovasc Transl Res. 2012 Jun;5(3):287-95. doi: 10.1007/s12265-012-9358-7. Epub 2012 Mar 29.
citation: Chaosuwannakit N, D'Agostino R Jr, Hamilton CA, Lane KS, Ntim WO, Lawrence J, Melin SA, Ellis LR, Torti FM, Little WC, Hundley WG. Aortic stiffness increases upon receipt of anthracycline chemotherapy. J Clin Oncol. 2010 Jan 1;28(1):166-72. doi: 10.1200/JCO.2009.23.8527. Epub 2009 Nov 9.
citation: Duquaine D, Hirsch GA, Chakrabarti A, Han Z, Kehrer C, Brook R, Joseph J, Schott A, Kalyanaraman B, Vasquez-Vivar J, Rajagopalan S. Rapid-onset endothelial dysfunction with adriamycin: evidence for a dysfunctional nitric oxide synthase. Vasc Med. 2003 May;8(2):101-7. doi: 10.1191/1358863x03vm476oa.