Impact of Severe Brain Injury on Neuro-vascular and Endothelial Regulation of Peripheral Microcirculation. (MicroTC)

Study of the Impact of Severe Brain Injury on the Neuro-vascular and Endothelial Regulation of Peripheral Microcirculation.

Severe brain injury (SBI) is one of the world's leading causes of death and disability in young adults, but its peripheral vascular consequences in humans are poorly understood.

This prospective, monocentric, pathophysiological study aims to investigate differences in vasoreactivity in the anterior aspect of the contralateral forearm at the most injured cerebral hemisphere between patients with severe head trauma and patients with severe trauma without associated brain injury matched on sex and age (+/- 5 years).

Study Overview

• Status: Recruiting
• Conditions: Trauma; Severe Traumatic Brain Injury

Detailed Description

Severe brain injury (SBI) is one of the world's leading causes of death and disability in young adults.

Its impact on cerebral vascularization is well known. At the systemic level, it induces transient dysfunctions that can develop into severe failures, even in cases of isolated SBI. Studies on a mouse model of SBI show alterations in peripheral vascular reactivity that persist over time and are linked to endothelial dysfunction, the mechanism of which is a decoupling of endothelial NO synthase in a context of systemic inflammation. However, no data are available regarding the peripheral vascular consequences of SBI in humans.

The main objective of this prospective, monocentric, pathophysiological study is to determine whether the postocclusive hyperaemic response at the anterior surface of the contralateral forearm to the most injured cerebral hemisphere differs between patients with severe brain injury and patients with severe trauma without associated head injury matched on sex and age (+/- 5 years), by studying the amplitude of post-occlusive hyperaemia (maximum amplitude expressed as percentage of vasodilatation and area under the curve : AUC) as a function of the group.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Jean-Luc Cracowski, Pr; Phone Number: 0033 0476767856; Email: JLCracowski@chu-grenoble.fr
• Study Contact Backup: Name: Manon Gabin, Intern; Phone Number: 0033 0476767575; Email: mgabin@chu-grenoble.fr

Study Locations

• France
  • Grenoble, France, 38700
    • Recruiting
    • University Hospital
    • Contact: Jean-Luc Cracowski, Pr; Phone Number: 0033 0476767856; Email: JLCracowski@chu-grenoble.fr
    • Contact: Manon Gabin, Intern; Phone Number: 0476767575; Email: mgabin@chu-grenoble.fr
    • Principal Investigator: Jean-Luc Cracowski, Pr
    • Sub-Investigator: Thibaut Trouve-Buisson, Dr
    • Sub-Investigator: Enkelejda Hodaj, Dr
    • Sub-Investigator: Claire Cracowski, Dr
    • Sub-Investigator: Manon Gabin, Intern

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

• Patients admitted for severe head trauma or severe trauma without associated severe head trauma in intensive care at Grenoble University Hospital.
• Healthy volunteers recruited through classified ads

Description

Inclusion Criteria:

Healthy volunteers :

• Men and women, over 18 years of age
• Affiliation to a social security scheme
• Signed Consent

Patients with Severe Brain Injury :

• Male and female, over 18 years of age
• Isolated severe brain injury, defined by an initial Glasgow score less than or equal to 8.
• Affiliation to a social security scheme
• Signed informed consent

Severe traumatized patients without associated severe brain injury:

• men and women, over 18 years of age
• severe trauma, defined by an Injury Severity Score (ISS) ≥ 16.
• absence of associated severe brain injury, defined by an initial Glasgow score less than or equal to 8.
• affiliation to or beneficiary of a social security scheme
• signed informed consent

Exclusion Criteria:

• Hypersensitivity to lidocaine and/or prilocaine or to amide type local anesthetics or to any of the excipients of the cream.
• History of axillary lymph node dissection, trauma or axillary surgery

• Prohibited treatments and procedures :

  • In patients with head trauma: ongoing treatment with systemic vasodilators (calcium channel blocker, milrinone).
  • In healthy volunteers: no treatment will be authorized other than paracetamol, hormone supplementation (contraceptive pill, hormone therapy, thyroid hormones).
• Pregnant, parturient or breastfeeding women
• Subject in a period of exclusion from another study,
• Person deprived of liberty by judicial or administrative decision, person subject to a legal protection measure,
• Subject having exceeded the annual compensation threshold for testing
• Subject cannot be contacted in case of emergency

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Healthy controls
Severe traumatic brain injury
Severe trauma without brain trauma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-occlusive hyperaemia	Maximum amplitude expressed as percentage of vasodilation and area under the curve: AUC	0-60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-occlusive hyperaemia with local anesthesia	Maximum amplitude expressed as percentage of vasodilation and area under the curve: AUC	0-60 days
Current-Induced Hyperaemia	Area under the curve expressed as a percentage of the baseline.	0-60 days
Current-Induced Hyperaemia with local anesthesia	Area under the curve expressed as a percentage of the baseline.	0-60 days
Local thermal hyperaemia	Maximum amplitude of the initial peak expressed as a percentage of the baseline and area under the curve of the delayed plateau.	0-60 days
Local thermal hyperaemia with local anesthesia	Maximum amplitude of the initial peak expressed as a percentage of the baseline and area under the curve of the delayed plateau.	0-60 days
Flow amplitude after local cooling	Amplitude of initial vasoconstriction averaged over 1 min around the lowest flow value during the first 5 minutes.	0-60 days
Transient venous post-compression hyperaemia	Area under the curve and percentage change from baseline.	0-60 days
Study of vasoreactivity in patients with severe brain injury	Extent of post-occlusive hyperaemia, current-induced hyperaemia, thermal hyperaemia and cold response in patients with severe brain injury.	0-60 days
Study of vasoreactivity in healthy subjects	Description of the magnitude of post-occlusive hyperaemia, current-induced hyperaemia, thermal hyperaemia and cold response in healthy subjects.	Study visit

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: Jean-Luc Cracowksi, Pr, University Hospital, Grenoble

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Actual): August 15, 2021
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: October 9, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Severe traumatic brain injury; Microcirculation; Brain trauma; Speckle; Post-occlusive reactive hyperaemia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: 2020-A00183-36; 38RC20.014 (Other Identifier: Promotor)

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