Interrupters of VAscular daMAge in Malignant Hypertension (IVAMA)

Interrupters of VAscular daMAge in Malignant Hypertension: Role of Inflammasome, Angiogenic and Vasoactive System

The pathophysiology of malignant hypertension is poorly understood. The objective of this translational research project is to evaluate the relationship between activation of vasoactive systems (renin-angiotensin and endothelin systems), angiogenic signal deficiency (VEGF and sFlt-1) and the occurrence of malignant hypertension episodes in humans.

Study Overview

• Status: Completed
• Conditions: Malignant Hypertension
• Intervention / Treatment: Biological: analyse of angiogenic, vasoactive and VEGF systems

Detailed Description

The pathophysiology of malignant hypertension is poorly understood. The current dogma is based on an overwhelming renin-angiotensin-aldosterone system activation, leading to arterial hypertension that overcomes target organ auto-regulatory mechanisms and leads to subacute microvascular lesions. However, some patients present with normal or lowered renin in the acute phase of malignant hypertension, suggesting other pathophysiological pathways. Malignant hypertension was reported following anti-VEGF treatment, suggesting that this pathway may be involved. Recent unpublished animal data highlight 1/ the possibility of severe deregulation of the VEGF (vascular endothelial growth factor) system in malignant hypertension 2/ the possibility of compensation of the vasculotoxic effects of VEGF deficiency by inflammasome components. These systems have never been studied together in human hypertension.

Investigators will analyze the angiogenic, vasoactive and VEGF systems through blood and urine sampling. These samples will be collected at the time of malignant hypertension diagnosis and repeated one month later in 30 patients. The same tests will be performed in 15 patients with severe non-malignant hypertension, constituting the control group.

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• France
  • Bobigny, France
    • Hôpital Avicenne
  • Bordeaux, France
    • CHU de Bordeaux
  • Paris, France
    • Hôpital Bichat
  • Paris, France
    • Hôpital Européen Georges Pompidou
  • Paris, France
    • Hopital Tenon
  • Toulouse, France
    • CHU Rangueil
  • Tours, France
    • CHU de Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patient group: patient with malignant hypertension control group: paitent with severe hypertension

Description

Inclusion Criteria:

Patients group :

• Patients included in the HAMA cohort
• Who is willing to take part in the IVAMA project

Control group :

• Grade 2 or 3 hypertension with office blood pressure measurement (above 160 and/or 100 mmHg for systolic and diastolic)
• Persistence of blood pressure above 160 / 100 mmHg on the average of 3 "attended" blood pressure measurements

Exclusion criteria:

Patients group :

• Age < 18 years old
• Patients with chronic renal failure of stage 3 or higher.
• Patients with any type of diabetes
• Patient in per partum
• Patients who cannot freely give their consent, or patients who refuse to participate
• Chronic dialysis patient

Control group:

• Evidence of subacute involvement of one of the following target organs: brain, kidney, eye, heart, thrombotic microangiopathy. Target organ impairment is defined in the inclusion criteria for the "Patients" group.
• Presence of known chronic kidney insufficiency of grade 3 or higher
• Chronic dialysis patient
• Diabetes of any type
• Patients who cannot freely give their consent, or patients who refuse to participate

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients group; patients with malignant hypertension	Biological: analyse of angiogenic, vasoactive and VEGF systems; the angiogenic, vasoactive and VEGF systems will be analysed through blood and urine sampling. These samples will be collected at the time of malignant hypertension diagnosis and repeated one month later, in 30 patients (patients group). The same tests will be performed once in 15 patients with severe non-malignant hypertension, constituting the control group.
Control group; patients with severe hypertension (Grade 2 or 3 hypertension)	Biological: analyse of angiogenic, vasoactive and VEGF systems; the angiogenic, vasoactive and VEGF systems will be analysed through blood and urine sampling. These samples will be collected at the time of malignant hypertension diagnosis and repeated one month later, in 30 patients (patients group). The same tests will be performed once in 15 patients with severe non-malignant hypertension, constituting the control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sFLT1 concentration at inclusion	The primary endpoint will be the difference in sFLT1 concentrations between patients and controls at enrolment	at the end of study recrutment, an average of 11 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL1ß concentration at inclusion	Difference in IL1ß concentrations between patients and controls at enrolment	at the end of study recrutment, an average of 11 month
VEGF concentration at inclusion	Difference in VEGF concentrations between patients and controls at enrolment	at the end of study recrutment, an average of 11 month
renin concentration at inclusion	Difference in renin concentrations between patients and controls at enrolmentD30, and compare this evolution.	at the end of study recrutment, an average of 11 month
angiotensin concentration at inclusion	Difference in angiotensin concentrations between patients and controls at enrolmentD30, and compare this evolution.	at the end of study recrutment, an average of 11 month
evolution of IL1ß concentration	Evaluation of the evolution of IL1ß concentration in the two groups between D0 and D30, and compare this evolution.	through study completion, an average of 12 month
evolution of VEGF concentration	Evaluation of the evolution of VEGF concentration in the two groups between D0 and D30, and compare this evolution.	through study completion, an average of 12 month
evolution of renin concentration	Evaluation of the evolution of renin concentration in the two groups between D0 and D30, and compare this evolution.	through study completion, an average of 12 month
evolution of angiotensin concentration	Evaluation of the evolution of angiotensin concentration in the two groups between D0 and D30, and compare this evolution.	through study completion, an average of 12 month
mutations in the genes of interest	comparison in the 2 groups of the frequency of mutations in the genes of interest underlying the vasoactive, angiogenic and VEGF systems	through study completion, an average of 11 month

Collaborators and Investigators

• Sponsor: Centre Hospitalier de PAU

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Actual): October 11, 2024
• Study Completion (Actual): October 11, 2024

Study Registration Dates

• First Submitted: June 16, 2021
• First Submitted That Met QC Criteria: July 27, 2021
• First Posted (Actual): August 5, 2021

Study Record Updates

• Last Update Posted (Actual): October 30, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: pathophysiology; inflammasome; severe hypertension; hypertensive emergency; malignant hypertension; angiogenic system
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Hypertension, Malignant
• Other Study ID Numbers: CHPAU2021/02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No