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Trial record 46 of 228 for:    EDN1

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
Sponsor:
Collaborator:
University of Glasgow
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde

Brief Summary:

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
Cardiovascular Diseases

Detailed Description:

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.


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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



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Change in plasma concentration of t-PA [ Time Frame: 105 minutes ]
    Change in plasma concentration of t-PA measured as units/mL

  2. Change in plasma concentration of PAI-1 [ Time Frame: 105 minutes ]
    Change in plasma concentration of PAI-1 measured as units/mL


Biospecimen Description:
Blood samples without DNA analysis


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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy volunteer males
Criteria

Inclusion Criteria:

  • healthy volunteer male
  • aged between 18 and 64 years

Exclusion Criteria:

  • Unable to provide written, informed consent
  • Unable or unwilling to attend for study assessments
  • Current involvement in a clinical trial
  • Severe or significant co-morbidity including:

    • Hypertension
    • Hyperlipidaemia
    • Cerebrovascular disease
    • Ischaemic heart disease or heart failure
    • Arial fibrillation/flutter
    • Venous or arterial thrombotic/thromboembolic event
    • Renal failure
    • Hepatic failure
  • Use of any prescription medication or non-steroidal anti-inflammatory drugs within the 3 days prior to vascular assessments
  • Cigarette smoker or tobacco use
  • Recreational drug use
  • History of anaemia
  • History of cancer
  • History of macular degeneration
  • Ongoing inflammatory, infective or autoimmune disease
  • Live vaccination received in the 3 months before the study, or expected to be required in the 6 months after the study
  • Unable or unwilling to use contraception with female partners in the 6 months after the study
  • BMI > 35 kg/m2
  • Unable to avoid blood donation for 1 week after the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03557190


Contacts
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Contact: alan cameron, MBChB 0141 330 8271 ext 8271 alan.cameron.2@glasgow.ac.uk
Contact: Katriona Brooksbank, PhD 0141 330 2418 katriona.brooksbank@glasgow.ac.uk

Locations
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United Kingdom
Queen Elizabeth University Hospital Recruiting
Glasgow, United Kingdom, G51 4TF
Contact: Alan Cameron, MBChB    0141 330 8271 ext 8271    alan.cameron.2@glasgow.ac.uk   
Contact: Katriona Brooksbank, PhD    0141 330 2418    katriona.brooksbank@glasgow.ac.uk   
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
University of Glasgow
Investigators
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Principal Investigator: Ninian Lang, MBChB PhD QEUH, NHS Greater Glasgow and Clyde

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Responsible Party: NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier: NCT03557190     History of Changes
Other Study ID Numbers: GN16CA026
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: June 14, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by NHS Greater Glasgow and Clyde:
VEGF inhibitors
hypertension
endothelial function
thrombosis
venous occlusion plethysmography
Additional relevant MeSH terms:
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Cardiovascular Diseases