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

Recruiting

• Conditions: Severe Traumatic Brain Injury; Trauma

• Registration Number: NCT04597879
• Lead Sponsor: University Hospital, Grenoble

Brief Summary

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).

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 Timeline

• Study First Submitted: 2020-10-09
• Study First Submitted QC: 2020-10-16
• Study First Posted: 2020-10-22
• Study Start: 2021-08-01
• Primary Completion: 2021-08-15
• Status Verified: 2022-10
• Last Update Submitted: 2022-11-02
• Last Update Posted: 2022-11-03
• Study Completion: 2023-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Post-occlusive hyperaemia	0-60 days	Maximum amplitude expressed as percentage of vasodilation and area under the curve: AUC

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University Hospital; 🇫🇷 Grenoble, France