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NCT Number: NCT04991077

Interrupters of VAscular daMAge in Malignant Hypertension

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Hôpital Avicenne, Bobigny, France

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About this study

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 Recent unpublished animal data highlight 1/ the possibility of severe deregulation of the VEGF (vascular endothelial growth factor) system in malignant hypertension 2/ the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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

analyse of angiogenic, vasoactive and VEGF systems

Biological

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.

Primary outcomes

  1. sFLT1 concentration at inclusion

    Time frame: at the end of study recrutment, an average of 11 month

    The primary endpoint will be the difference in sFLT1 concentrations between patients and controls at enrolment

Secondary outcomes

  1. IL1ß concentration at inclusion

    Time frame: at the end of study recrutment, an average of 11 month

    Difference in IL1ß concentrations between patients and controls at enrolment

  2. VEGF concentration at inclusion

    Time frame: at the end of study recrutment, an average of 11 month

    Difference in VEGF concentrations between patients and controls at enrolment

  3. renin concentration at inclusion

    Time frame: at the end of study recrutment, an average of 11 month

    Difference in renin concentrations between patients and controls at enrolmentD30, and compare this evolution.

  4. angiotensin concentration at inclusion

    Time frame: at the end of study recrutment, an average of 11 month

    Difference in angiotensin concentrations between patients and controls at enrolmentD30, and compare this evolution.

  5. evolution of IL1ß concentration

    Time frame: through study completion, an average of 12 month

    Evaluation of the evolution of IL1ß concentration in the two groups between D0 and D30, and compare this evolution.

  6. evolution of VEGF concentration

    Time frame: through study completion, an average of 12 month

    Evaluation of the evolution of VEGF concentration in the two groups between D0 and D30, and compare this evolution.

  7. evolution of renin concentration

    Time frame: through study completion, an average of 12 month

    Evaluation of the evolution of renin concentration in the two groups between D0 and D30, and compare this evolution.

  8. evolution of angiotensin concentration

    Time frame: through study completion, an average of 12 month

    Evaluation of the evolution of angiotensin concentration in the two groups between D0 and D30, and compare this evolution.

  9. mutations in the genes of interest

    Time frame: through study completion, an average of 11 month

    comparison in the 2 groups of the frequency of mutations in the genes of interest underlying the vasoactive, angiogenic and VEGF systems

Sponsors and collaborators

Lead sponsor

Centre Hospitalier de PAU

Other

Registry information

Official study title

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

Acronym: IVAMA

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Aug 5, 2021
Registry last updated
Oct 30, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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