Endothelial Effects of VEGF Inhibition In Vivo in Man (ENDEAVOUR)
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|ClinicalTrials.gov Identifier: NCT03557190|
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : June 14, 2018
Recent developments in chemotherapy, particularly VEGF-inhibitor (VEGFI) drugs, have markedly improved the prognosis of patients with cancer. However, these drugs frequently cause high blood pressure (hypertension) which can lead to heart attacks, heart failure and stroke and can limit their use for cancer treatment.
Endothelin-1 is a hormone that causes blood vessels to tighten and may contribute to high blood pressure associated with VEGFI drugs. Blocking the effects of endothelin-1 may therefore reduce or prevent VEGFI-associated blood pressure changes, although this has never been tested in humans.
Our long-term goal is to assess the protective effects of endothelin-1 blocker drugs in patients treated with VEGFI. Before doing so, we must better explore whether VEGFIs cause blood vessel narrowing and if endothelin-1 blockers prevent this. We will assess this in healthy volunteers using a special technique called 'forearm plethysmography'. We will examine the effect of VEGFI on blood flow and also the effect of simultaneous administration of endothelin-1 blockers. These will be given at doses that produce local effects in the arm without affecting the rest of the body.
These studies study will show whether endothelin-1 blockers may help treat VEGFI-associated hypertension to enable more patients safely to receive vital cancer treatments.
|Condition or disease|
Developments in chemotherapy have improved the prognosis for patients with cancer.1,2 Angiogenesis is essential for tumour growth and metastasis and vascular endothelial growth factor (VEGF) is fundamental to this process.3,4 Chemotherapeutic VEGF inhibitor (VEGFI) drugs have revolutionised therapy and improved the prognosis and survival of patients with previously untreatable malignancies.1,2 Blood pressure elevation is a common complication that occurs in up to 80% of patients treated with VEGFI and almost all patients have an absolute increase in blood pressure, with 30-60% developing frank hypertension.1,5 Patients are at risk of acute hypertensive complications, including stroke, acute coronary syndrome or reversible leukoencephalopathy and the development of VEGFI-associated hypertension may mandate the premature discontinuation of these important anti-cancer therapies. Those who survive their cancer are at risk of developing end-organ damage leading to ischaemic heart disease, heart failure, renal failure and stroke.1,5 Indeed, with substantially increased cancer survivorship patients often survive long enough to allow cardiovascular morbidity to take precedence over their initial cancer diagnosis.
Mechanisms contributing to the development of VEGFI-associated hypertension may include endothelial dysfunction, capillary rarefaction and vascular remodelling.1,5 Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor and is strongly implicated in the pathogenesis of hypertension and endothelial dysfunction. 3,6,7 However, the effects of VEGFI on endothelial function and the role of ET-1 in VEGFI-associated hypertension are incompletely defined. Indeed, there is a paucity of information on mechanisms contributing to VEGFI-induced hypertension and our study will address this key issue.
|Study Type :||Observational|
|Estimated Enrollment :||56 participants|
|Official Title:||Novel Cancer Chemotherapeutics and the Vasculature: Endothelial Effects of VEGF Inhibition In Vivo in Man|
|Actual Study Start Date :||December 1, 2016|
|Estimated Primary Completion Date :||July 1, 2018|
|Estimated Study Completion Date :||July 1, 2018|
- Change in forearm blood flow [ Time Frame: 105 minutes ]Study drugs will be infused intra-arterially and forearm arterial blood flow assessed using forearm venous occlusion plethysmography expressed as ml per 100 ml of forearm volume per minute
- Change in plasma concentration of t-PA [ Time Frame: 105 minutes ]Change in plasma concentration of t-PA measured as units/mL
- Change in plasma concentration of PAI-1 [ Time Frame: 105 minutes ]Change in plasma concentration of PAI-1 measured as units/mL
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03557190
|Contact: alan cameron, MBChB||0141 330 8271 ext firstname.lastname@example.org|
|Contact: Katriona Brooksbank, PhD||0141 330 email@example.com|
|Queen Elizabeth University Hospital||Recruiting|
|Glasgow, United Kingdom, G51 4TF|
|Contact: Alan Cameron, MBChB 0141 330 8271 ext 8271 firstname.lastname@example.org|
|Contact: Katriona Brooksbank, PhD 0141 330 2418 email@example.com|
|Principal Investigator:||Ninian Lang, MBChB PhD||QEUH, NHS Greater Glasgow and Clyde|