Bevacizumab and Endothelium Dependent Vasodilation

Study Overview
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Brief Summary
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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.

Official Title
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Bevacizumab and Endothelium Dependent Vasodilation

Conditions
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Hypertension, Cancer, Endothelial Dysfunction

Intervention / Treatment
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* Drug: Acetylcholine
* Drug: Nitroprusside
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-50 years old Male Results of serum glucose, lipids and creatinine should be within the laboratory's reference ranges. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations. Exclusion Criteria: Documented history of sensitivity/idiosyncrasy to medicinal products or excipients. History of or current abuse of drugs, alcohol or solvents. History of malignant disease. First degree relatives with a history of cancer before the age of 50 First degree relatives with a history of premature cardiovascular disease before the age of 50 Current use of medication. Clinical evidence of cardiac or pulmonary disease Hypertension ( systole >140mmHG, diastole >90mmHg) Diabetes mellitus Smoking Any clinically relevant abnormality on ECG. A history of thrombosis or first degree family members with a history of recurrent thrombosis Inability to understand the nature and extent of the trial and the procedures required. Previous participation in a study with bevacizumab

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetylcholine<br>Intra-arterial infusion of acetylcholine in two increasing dosages during 5 minutes each during the intra-arterial infusion of bevacizumab | Drug: Acetylcholine<br>* Intra-arterial infusion<br>Drug: Bevacizumab<br>* Intra arterial infusion<br>|
| Experimental: Nitroprusside<br>Infusion of two increasing dosages of nitroprusside during 5 minutes each during the continuous infusion of bevacizumab | Drug: Nitroprusside<br>* Intra arterial infusion<br>Drug: Bevacizumab<br>* Intra arterial infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vasomotor response assessed by venous occlusion strain gauge plethysmography | Response to infusion of bevacizumab and/or acetylcholin or nitroprusside | 15 minutes |