Cardiovascular DiseasesENDEAVOURNCT03557190
Endothelial Effects of VEGF Inhibition In Vivo in Man
An observational study of Cardiovascular Diseases, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases
- How many people
- 56 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Dec 2016to 1 Jul 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- Men only
- Healthy volunteers accepted
- Adult
Study population: Healthy volunteer males
Who may be able to join
- healthy volunteer male
- aged between 18 and 64 years
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Queen Elizabeth University Hospital
Glasgow, G51 4TF
About this study
Official title: Novel Cancer Chemotherapeutics and the Vasculature: Endothelial Effects of VEGF Inhibition In Vivo in Man
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.
Read more
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.
Read the 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.
- Conditions
- Cardiovascular Diseases
- Keywords
- VEGF inhibitors, hypertension, endothelial function, thrombosis, venous occlusion plethysmography
- Medical subject headings
- Cardiovascular Diseases, Hypertension, Thrombosis
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in forearm blood flow
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
Measured: 105 minutes
Secondary outcomes (2)
Change in plasma concentration of t-PA
Change in plasma concentration of t-PA measured as units/mL
Measured: 105 minutes
Change in plasma concentration of PAI-1
Change in plasma concentration of PAI-1 measured as units/mL
Measured: 105 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2018
- Study start1 Dec 2016
- Primary completion1 Jul 2018
- Study completion1 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow
- Responsible party
- Sponsor
- Investigators
- Ninian Lang, MBChB PhD, Principal investigator, QEUH, NHS Greater Glasgow and Clyde
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03557190
- Sponsor's protocol ID
- GN16CA026
- Acronym
- ENDEAVOUR
- Status last verified
- Nov 2019
- First submitted
- 4 Jun 2018
- Last updated
- 26 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Cancer Chemotherapeutics and the Vasculature: Endothelial Effects of VEGF Inhibition In Vivo in Man
- ClinicalTrials.gov ID
- NCT03557190
- Acronym / sponsor ID
- ENDEAVOUR / GN16CA026
- Conditions
- Cardiovascular Diseases
- Keywords
- VEGF inhibitors, hypertension, endothelial function, thrombosis, venous occlusion plethysmography
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Collaborators
- University of Glasgow
- Study start
- 1 Dec 2016 (actual)
- Primary completion
- 1 Jul 2018 (actual)
- Study completion
- 1 Jul 2018 (actual)
- First posted
- 14 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 64 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Healthy volunteer males
Key inclusion criteria (2 listed)
- healthy volunteer male
- aged between 18 and 64 years
Key exclusion criteria (23 listed)
- 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:
- Use of any prescription medication or non-steroidal anti-inflammatory drugs within the 3 days prior to vascular assessments
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
2 secondary outcomes
Change in plasma concentration of t-PA
Time frame: 105 minutes
Change in plasma concentration of PAI-1
Time frame: 105 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ninian Lang, MBChB PhD principal investigator
QEUH, NHS Greater Glasgow and Clyde
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in forearm blood flow (time frame: 105 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2019.