Interrupters of VAscular daMAge in Malignant Hypertension

Malignant Hypertension Clinical Trial

— IVAMA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04991077
• Other study ID #: CHPAU2021/02
• Status: Recruiting
• Start date: February 7, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Centre Hospitalier de PAU
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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 Recent unpublished animal data highlight 1/ the possibility of severe deregulation of the VEGF (vascular endothelial growth factor) system in malignant hypertension 2/ the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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Malignant
• Malignant Hypertension

Intervention

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.

Locations

Country	Name	City	State
France	Hôpital Avicenne	Bobigny
France	CHU de Bordeaux	Bordeaux
France	Hôpital Bichat	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Tenon	Paris
France	Chu Rangueil	Toulouse
France	CHU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier de PAU

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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