To determine the effect of bevacizumab on vascular tone in humans by using plethysmography.
ID
Source
Brief title
Condition
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The fore-arm vasomotor response to administered bevacizumab, expressed as
percentage change in forerarm blood flow ratio ( flow infused arm flow control
arm form baseline
Secondary outcome
Correlation between VEGF concentrations in plasma and the vasoconstrictive
response to bevacizumab
Background 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.
One of the main targets of angiogenesis-inhibitors is vascular endothelial
growth factor and its receptors. Animal and human studies show that VEGF
induces vasodilation and hypotension by stimulation of NO production.
Furthermore animal studies suggest that endogenous VEGF may play a role in
maintaining normal vascular tone in blood vessels.
Theoretically inhibition of VEGF or VEGFr in humans would decrease NO
production causing vasoconstriction and thereby induce hypertension.
Study objective
To determine the effect of bevacizumab on vascular tone in humans by using
plethysmography.
Study design
This is a single center, intervention pilot study
Vasoconstriction assessed by venous occlusion strain gauge plethysmography
during bevacizumab infusion and serum VEGF levels pre-study.
Intervention
Intra-arterial infusion of bevacizumab
Study burden and risks
Intra-arterial infusion of bevacizumab allows the use of very low cumulative
doses that reach local concentrations in the infused forearm that are
sufficient to induce a local effect with very low systemic concentrations. In a
study to evaluate the short-term safety of systemic bevacizumab (5mg/kg) in
patients with age-related macular degeneration no adverse events were reported
except hypertension.
During plethysmography, wrist cuffs are inflated to exclude the hand (mainly
skin) circulation from the experimental preparation. This will cause rapidly
reversible numbness and discomfort in both hands due to inflation of the
wrist-cuffs. The subjects will not benefit directly from participating in this
study.
Postbus 9101
6500HB Nijmegen
Nederland
Postbus 9101
6500HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
1. Age 18-50years 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. Current use of medication.
6. Clinical evidence of cardiac or pulmonary disease
7. Hypertension ( systole >140mmHG, diastole >90mmHg)
8. Diabetes mellitus
9. Smoking
10. Any clinically relevant abnormality on ECG.
11. Inability to understand the nature and extent of the trial and the procedures required.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-010600-28-NL |
| CCMO | NL27013.091.09 |