Cardiovascular Function in Cancer Survivors

Study Overview
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Brief Summary
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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
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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.

Official Title
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Therapeutic Role of Dietary Nitrates on Cardiovascular Function in Cancer Survivors Treated With Anthracycline Chemotherapy

Conditions
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Cancer Survivor With History of Anthracycline Chemotherapy

Intervention / Treatment
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* Dietary Supplement: Beetroot juice
* Dietary Supplement: Black currant juice


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Beetroot juice (dietary nitrate)<br>Over the 7 days preceding each testing session, participants will consume 140 ml per day of beetroot juice (Beet It (HeartBeet Ltd.), Ipswich, UK). During this time participants will be asked to abstain from use of antiseptic mouthwash as this has been shown to temporarily kill the bacteria that facilitate the reduction of nitrate to nitrite. All participants will be asked to refrain from consuming any antioxidant (e.g., Vit E or Fish Oil) supplements during the course of the study as these may impact the study findings. | Dietary Supplement: Beetroot juice<br>* Following randomization on day 1, subjects will consume either the nitrate or nitrate-free beverage for 7 days with outcome measurements performed on day 7. Following a 7 day washout, subjects will then consume the crossover beverage for 7 days with outcome measures performed on day 21.<br>|
| Placebo Comparator: Black currant juice (placebo control)<br>Over the 7 days preceding each testing session, participants will consume 140 ml per day of a nitrate-depleted placebo. During this time participants will be asked to abstain from use of antiseptic mouthwash as this has been shown to temporarily kill the bacteria that facilitate the reduction of nitrate to nitrite. All participants will be asked to refrain from consuming any antioxidant (e.g., Vit E or Fish Oil) supplements during the course of the study as these may impact the study findings. | Dietary Supplement: Black currant juice<br>* Following randomization on day 1, subjects will consume either the nitrate or nitrate-free beverage for 7 days with outcome measurements performed on day 7. Following a 7 day washout, subjects will then consume the crossover beverage for 7 days with outcome measures performed on day 21.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Left ventricular function | Left ventricular function as measured by transthoracic echocardiography | The change between day 1 and day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vascular function | Vascular function measured as changes in arterial stiffness and endothelial function. | The change between day 1 and day 21 | 
| Change in Blood pressure | Local limb blood pressure measured in millimeters of mercury (mmHg) following study interventions/arms | The change between day 1 and day 21 |