Bevacizumab and Endothelium Dependent Vasodilation

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Cancer; Endothelial Dysfunction
• Intervention / Treatment: Drug: Acetylcholine; Drug: Bevacizumab; Drug: Nitroprusside

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboud University Nijmegen Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Age 18-50 years old
2. Male
3. Results of serum glucose, lipids and creatinine should be within the laboratory's reference ranges.
4. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.

Exclusion Criteria:

1. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
2. History of or current abuse of drugs, alcohol or solvents.
3. History of malignant disease.
4. First degree relatives with a history of cancer before the age of 50
5. First degree relatives with a history of premature cardiovascular disease before the age of 50
6. Current use of medication.
7. Clinical evidence of cardiac or pulmonary disease
8. Hypertension ( systole >140mmHG, diastole >90mmHg)
9. Diabetes mellitus
10. Smoking
11. Any clinically relevant abnormality on ECG.
12. A history of thrombosis or first degree family members with a history of recurrent thrombosis
13. Inability to understand the nature and extent of the trial and the procedures required.
14. Previous participation in a study with bevacizumab

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Dutch Cancer Society

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: May 17, 2010
• First Submitted That Met QC Criteria: May 17, 2010
• First Posted (Estimate): May 19, 2010

Study Record Updates

• Last Update Posted (Estimate): January 10, 2013
• Last Update Submitted That Met QC Criteria: January 8, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Cholinergic Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Cholinergic Agonists; Nitric Oxide Donors; Bevacizumab; Nitroprusside; Acetylcholine
• Other Study ID Numbers: BVZAch