Heart and Blood Diseases

All Conditions

Hypertension

Vascular Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antihypertensive Agents

Nitric Oxide Donors

Vasodilator Agents

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Bevacizumab

Nitroprusside

Acetylcholine

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Nitric Oxide

Cholinergic Agents

Neurotransmitter Agents

Intra-arterial infusion of acetylcholine in two increasing dosages during 5 minutes each during the intra-arterial infusion of bevacizumab

Infusion of two increasing dosages of nitroprusside during 5 minutes each during the continuous infusion of bevacizumab

The introduction of angiogenesis inhibitors has remarkably improved treatment of patients with several types of cancer. One of the most reported side effects of angiogenesis inhibitors is hypertension. In patients treated with bevacizumab, a monoclonal antibody against vascular endothelial growth factor, hypertension had an overall incidence up to 32%. The increase in blood pressure occurs early in treatment. The etiology of hypertension caused by treatment with angiogenesis inhibitors is unclear. Understanding the pathogenesis of this side effect is essential for optimal treatment with this class of drugs.

The primary objective is to explore the effect of bevacizumab infusion on endothelium-dependent vasodilation of forearm resistance arteries.

Bevacizumab and Endothelium Dependent Vasodilation

Response to infusion of bevacizumab and/or acetylcholin or nitroprusside

Dutch Cancer Society

Radboud University Medical Center

Prof dr. G. Rongen

Neoplasms

Skin and Connective Tissue Diseases

Leiomyoma

Myofibroma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Connective Tissue Diseases

Vasoconstrictor Agents

Cardiotonic Agents

Central Nervous System Stimulants

Norepinephrine

Oxymetazoline

Phenylephrine

Mydriatics

Sympathomimetics

Ephedrine

Pseudoephedrine

Nasal Decongestants

Adrenergic Agents

Adrenergic alpha-Agonists

Adrenergic Agonists

Protective Agents

* Brachial artery catheter
* Acetylcholine
* Nitroprusside
* Norepinephrine
* Nitroprusside and phenylephrine

A catheter will be placed in the brachial artery by a physician on the study day.

Brachial artery catheter

Acetylcholine will be infused into the brachial catheter while blood flow levels in the forearm are measured. Acetylcholine will be infused at the following doses: 1.0, 2.0, 4.0, and 8.0 ug/100 ml tissue/min for 2 minutes each.

Nitroprusside will be infused into the brachial catheter while blood flow levels in the forearm are measured. Nitroprusside will be infused at the following doses: 0.25, 0.5, 1.0, and 2.0 ug/100 ml tissue/min for 2 minutes each.

Norepinephrine will be infused into the brachial catheter while blood flow levels in the forearm are measured. Norepinephrine will be infused at the following doses: 1.0, 2.0, 4.0, and 8.0 ug/100 ml tissue/min for 2 minutes each.

A single dose of nitroprusside (100 ug) will be infused through an IV; one minute later, a single dose of phenylephrine (150 ug) will be infused.

Nitroprusside and phenylephrine

Michael J Joyner, M.D.

The purpose of this study is to learn how uterine fibroids may be connected to heart disease and high blood pressure. It is not known what causes fibroids, but they frequently occur in women who also have high blood pressure, heart disease, and stroke. The investigators of this study want to learn if certain changes in the blood vessels or nerve activity can put women at risk for these diseases and for fibroids.

The investigators are inviting women, 25-50 years old, who have not gone through menopause to participate in this study. The investigators are looking for some women with uterine fibroids and some without uterine fibroids based on ultrasound or MRI. If the patients have not had a recent ultrasound or MRI of the uterus, a physician can provide one.

Individuals cannot participate if they have high blood pressure, diabetes, or disease in the kidneys, lungs, or blood vessels. Also, individuals who smoke, have high cholesterol, or are obese (BMI is higher than 30) cannot participate. Certain medications, including high blood pressure medications, beta-blockers and anti-depressants, will also limit potential patient participation. The investigators would be happy to review medications for potential participants.

Screen Day:

One of the members of the research team will review the study and the informed consent document with the patient. The patient will have their height, weight, blood pressure, pulse and respirations measured. The patient will also complete three questionnaires. If the patient has not had an ultrasound of the uterus in the last 12 months, a physician will complete one for her.

Study Day:

The patient will need to fast overnight (no eating or drinking). The investigators will draw a blood sample and then do a series of tests on the participant's blood vessels. For some of the tests, medication will be given through an IV. The investigators will also test nerve activity in the nerve on the outer aspect of the leg.

Whole blood and serum

No DNA extraction from samples is planned.

Vascular Function and Uterine Fibroids

Sympathetic Nerve Activity and Vascular Function in Women With Uterine Leiomyomata

Blood samples will be collected to measure levels of estrogen and progesterone.

Nerve "burst" activity will be measured across 10 minutes.

An infusion of nitroprusside will be given, followed by an infusion of phenylephrine one minute later.

Mayo Clinic

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Breast Neoplasms

Lymphoma

Leukemia

Lymphosarcoma

Amino Acids

Arginine

Participants install the HeartPhone app on their smartphone. This app presents an image on a splash screen every time they activate their device. The image is randomly drawn from an image bank in the app. Repeated exposure to the image is designed to condition a more favorable automatic affective evaluation of physical activity and lead to increased physical activity.

Evaluative conditioning (temporally distributed micro-doses presented upon activation of smartphone screen)

HeartPhone app

Endothelium-dependent vasodilation is tested with the localized delivery of the neurotransmitter

Endothelium-independent vasodilation is tested with the localized delivery of the nitric oxide donor

Sodium Nitroprusside

This nitric oxide inhibitor is continuously given during the localized delivery of the endothelium-dependent agonist acetycholine.

L-Arginine, N2-((4-Methylphenyl)Sulfonyl)-, Methyl Ester

This is a behavioral study that will examine changes in physical activity and vascular health in response to a digital tool (app) that will appear on participant's lock screen of their Android phone. Participants will be asked to use this app for 3 months and to wear a Fitbit device continuously throughout the study. Participants will be asked to complete questionnaires, participate in fitness testing and measures of cardiovascular health at 3 months and 6 months after baseline assessments. The hypothesis is that exposure to the app will lead to increased physical activity volume and improved microvessel function.

HeartPhone Cancer Survivors Trial 2019

Digital Intervention to Promote Physical Activity and Improve Cardiovascular Health Among Cancer Survivors

Daily step counts over 1-week from Fitbit device

Skin blood flow during perfusion of endothelium-dependent and independent agonists

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bevacizumab and Endothelium Dependent Vasodilation	NCT01125943	Hypertension Cancer Endothelial Dys...	Acetylcholine Nitroprusside Bevacizumab	18 Years - 50 Years	Radboud University Medical Center
Bevacizumab and Endothelium Dependent Vasodilation	NCT01125943	Hypertension Cancer Endothelial Dys...	Acetylcholine Nitroprusside Bevacizumab	18 Years - 50 Years	Radboud University Medical Center
Vascular Function and Uterine Fibroids	NCT02123069	Leiomyoma	Brachial artery... Acetylcholine Nitroprusside Norepinephrine Nitroprusside a...	25 Years - 50 Years	Mayo Clinic
HeartPhone Cancer Survivors Trial 2019	NCT03953326	Breast Cancer Leukemia Lymphoma	HeartPhone app Acetylcholine Sodium Nitropru... L-Arginine, N2-...	18 Years - 65 Years	Penn State University

Spots Global Cancer Trial Database for acetylcholine