Endothelial Effects of VEGF Inhibition In Vivo in Man

NCT03557190 | Completed

• 1 other identifier: GN16CA026
• Study Type: observational
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Diseases

Keywords

VEGF inhibitors; hypertension; endothelial function; thrombosis; venous occlusion plethysmography

Outcome Measures

Primary Outcomes (1)

• 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

  105 minutes

Secondary Outcomes (2)

• Change in plasma concentration of t-PA

  105 minutes

• Change in plasma concentration of PAI-1

  105 minutes

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteer males

You may qualify if:

• healthy volunteer male
• aged between 18 and 64 years

You may not qualify if:

• 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

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Glasgow: collaborator

Study Sites (1)

Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples without DNA analysis

MeSH Terms

Conditions

Cardiovascular Diseases; Hypertension; Thrombosis

Condition Hierarchy (Ancestors)

Vascular Diseases; Embolism and Thrombosis

Study Officials

• Ninian Lang, MBChB PhD

  QEUH, NHS Greater Glasgow and Clyde

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2018
• First Posted: June 14, 2018
• Study Start: December 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: November 26, 2019

Record last verified: 2019-11

Locations

GB (1)