Novel Mechanisms and Predictors of VEGF Receptor Inhibitor- or Immune Checkpoint Inhibitor-Associated Hypertension and Cardiovascular Disease

The purpose of this study is to understand the effect of vascular endothelial growth factor tyrosine kinase (VEGF) inhibitor, immune checkpoint-inhibitor (ICI), and combination treatment on blood pressure and blood vessel function.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Renal Cell Carcinoma; Hypertension; Cancer
• Intervention / Treatment: Diagnostic test: Ambulatory Blood Pressure Measurement

• Study Type: Observational
• Enrollment (Actual): 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants with cancer that will be receiving VEGF inhibitor, ICI, or combination (VEGF inhibitor plus ICI or combination ICI treatment), or not receiving any treatment.

Description

Inclusion Criteria:

• Male or female, age 40 - 75 years old
• Diagnosis of cancer
• Receiving VEGF inhibitor, ICI, or combination (VEGF inhibitor + ICI or combination ICI) treatment, or not receiving any treatment.
• Normal blood pressure or blood pressure treated to < 140/90 mm Hg with ≤2 antihypertensive medications

Exclusion Criteria:

• Presence of peripheral artery disease
• History of a heart attack within 1 year
• History of a stroke within 1 year
• Diabetes
• Life expectancy < 3 months
• Women who are pregnant
• Women who are nursing

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
VEGF inhibitor alone	Diagnostic test: Ambulatory Blood Pressure Measurement; Baseline: Subjects will undergo an abbreviated physical exam, review changes in medical history since last oncology visit, blood collection, urine collection, blood pressure and heart rate in triplicate, baseline and hyperemic digital velocity time interval (VTI) using pulse amplitude tonometry, cubital vein endothelial cell harvest, and ambulatory 24 blood pressure measurement. Follow-up Visit (approx 1 month after starting treatment): Review changes in medications and any medical events that happened since the last visit, an abbreviated physical exam, blood collection, urine collection, blood pressure and heart rate in triplicate, baseline and hyperemic velocity time interval (VTI), digital pulse amplitude tonometry, endothelial cell harvest, and ambulatory 24 blood pressure.
Immune Checkpoint Inhibitor (ICI) alone	Diagnostic test: Ambulatory Blood Pressure Measurement; Baseline: Subjects will undergo an abbreviated physical exam, review changes in medical history since last oncology visit, blood collection, urine collection, blood pressure and heart rate in triplicate, baseline and hyperemic digital velocity time interval (VTI) using pulse amplitude tonometry, cubital vein endothelial cell harvest, and ambulatory 24 blood pressure measurement. Follow-up Visit (approx 1 month after starting treatment): Review changes in medications and any medical events that happened since the last visit, an abbreviated physical exam, blood collection, urine collection, blood pressure and heart rate in triplicate, baseline and hyperemic velocity time interval (VTI), digital pulse amplitude tonometry, endothelial cell harvest, and ambulatory 24 blood pressure.
Combination (VEGF inhibitor + ICI, or combination of ICI)	Diagnostic test: Ambulatory Blood Pressure Measurement; Baseline: Subjects will undergo an abbreviated physical exam, review changes in medical history since last oncology visit, blood collection, urine collection, blood pressure and heart rate in triplicate, baseline and hyperemic digital velocity time interval (VTI) using pulse amplitude tonometry, cubital vein endothelial cell harvest, and ambulatory 24 blood pressure measurement. Follow-up Visit (approx 1 month after starting treatment): Review changes in medications and any medical events that happened since the last visit, an abbreviated physical exam, blood collection, urine collection, blood pressure and heart rate in triplicate, baseline and hyperemic velocity time interval (VTI), digital pulse amplitude tonometry, endothelial cell harvest, and ambulatory 24 blood pressure.
No treatment	Diagnostic test: Ambulatory Blood Pressure Measurement; Baseline: Subjects will undergo an abbreviated physical exam, review changes in medical history since last oncology visit, blood collection, urine collection, blood pressure and heart rate in triplicate, baseline and hyperemic digital velocity time interval (VTI) using pulse amplitude tonometry, cubital vein endothelial cell harvest, and ambulatory 24 blood pressure measurement. Follow-up Visit (approx 1 month after starting treatment): Review changes in medications and any medical events that happened since the last visit, an abbreviated physical exam, blood collection, urine collection, blood pressure and heart rate in triplicate, baseline and hyperemic velocity time interval (VTI), digital pulse amplitude tonometry, endothelial cell harvest, and ambulatory 24 blood pressure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Blood Pressure	Mean 24 hour blood pressure from ambulatory 24 hour recording	Baseline and 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of Post-treatment to Pre-treatment Change in Digital Pulse Amplitude	Digital pulse amplitude will be measured using peripheral artery tonometry	Baseline and 1 month

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Joshua Beckman, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2020
• Primary Completion (Actual): October 1, 2020
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: October 15, 2018
• First Submitted That Met QC Criteria: October 15, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Hypertension; Cardiovascular Diseases
• Other Study ID Numbers: 181796

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No