Bevacizumab and Endothelium Dependent Vasodilation

NCT01125943 | Completed

• 1 other identifier: BVZAch
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertension; Cancer; Endothelial Dysfunction

Outcome Measures

Primary Outcomes (1)

• Vasomotor response assessed by venous occlusion strain gauge plethysmography

  Response to infusion of bevacizumab and/or acetylcholin or nitroprusside

  15 minutes

Study Arms (2)

Acetylcholine

EXPERIMENTAL

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

Drug: Acetylcholine; Drug: Bevacizumab

Nitroprusside

EXPERIMENTAL

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

Drug: Nitroprusside; Drug: Bevacizumab

Interventions

Acetylcholine DRUG

Intra-arterial infusion

Acetylcholine

Nitroprusside DRUG

Intra arterial infusion

Nitroprusside

Bevacizumab DRUG

Intra arterial infusion

Acetylcholine; Nitroprusside

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Dutch Cancer Society: collaborator

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands

Location

MeSH Terms

Conditions

Hypertension; Neoplasms

Interventions

Acetylcholine; Nitroprusside; Bevacizumab

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biogenic Amines; Amines; Organic Chemicals; Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof dr. G. Rongen

Study Record Dates

• First Submitted: May 17, 2010
• First Posted: May 19, 2010
• Study Start: June 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: November 1, 2011
• Last Updated: January 10, 2013

Record last verified: 2013-01

Locations

NL (1)