Systemic Nitrosative/Oxidative Stress in Patients with Acute Brain Injury

NCT04951453 | Active Not Recruiting

• 1 other identifier: H-21004729
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Acute brain injury due to traumatic brain injury (TBI), intracerebral haemorrhage (ICH), and aneurysmal subarachnoid haemorrhage (SAH) carries a high morbidity and mortality, in part due to the development of secondary brain injury. The mechanisms behind secondary brain injury are incompletely understood, but oxidative/nitrosative stress and disturbances in the metabolism of the vasodilator nitric oxide (NO) are believed to be involved. The aim of the present study is to characterise systemic changes in markers of oxidative/nitrosative stress and NO metabolism in the early phase after acute brain injury, and to examine their relationship to clinical course, neurological outcome, and mortality.

Conditions

Subarachnoid Hemorrhage, Aneurysmal; Intracerebral Hemorrhage; Traumatic Brain Injury

Keywords

Nitrosative Stress; Oxidative Stress; Nitric Oxide; Acute Brain Injury; Subarachnoid Hemorrhage; Intracerebral Hemorrhage; Traumatic Brain Injury; Secondary Brain Injury; Neuromonitoring

Outcome Measures

Primary Outcomes (1)

• Neurological outcome (modified Rankin scale)

  Neurological outcome as assessed using the modified Rankin Scale, which measures the degree of disability on a scale from 0 to 6 (higher score indicates a worse outcome)

  6 months

Secondary Outcomes (3)

• Mortality

  6 months

• Neuroworsening

  Within 14 days

• Delayed Cerebral Ischaemia (DCI)

  Within 14 days

Other Outcomes (7)

• Levels of brain injury biomarkers

  Within 14 days

• Angiographic vasospasm

  Within 14 days

• Length of stay

  During hospitalisation

Study Arms (3)

Aneurysmal subarachnoid haemorrhage

Patients with SAH (see eligibility criteria below). Planned enrollment: 50 patients.

Other: None (observational)

Intracerebral haemorrhage

Patients with ICH (see eligibility criteria below). Planned enrollment: 50 patients.

Other: None (observational)

Traumatic Brain Injury

Patients with TBI (see eligibility criteria below). Planned enrollment: 50 patients.

Other: None (observational)

Interventions

None (observational) OTHER

None (observational)

Aneurysmal subarachnoid haemorrhage; Intracerebral haemorrhage; Traumatic Brain Injury

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with acute brain injury (SAH, ICH or TBI) admitted to the NICU at Rigshospitalet - see detailed inclusion and exclusion criteria above.

You may qualify if:

• Admission to the Neurointensive Care Unit (NICU) at Rigshospitalet
• Diagnosis of TBI, spontaneous ICH or aneurysmal SAH
• Initiation of blood sampling possible within 3 days after ictus
• Expected length of stay in the NICU and/or intermediate care unit of ≥48 hours
• Closest relatives understand written and spoken Danish

You may not qualify if:

• Expected death within 24 hours
• ICH secondary to other causes (e.g., a tumour or arteriovenous malformation)
• SAH secondary to other causes (e.g., a mycotic aneurysm or arteriovenous malformation)

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• University of South Wales: collaborator

Study Sites (1)

Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Related Publications (16)

• Morris GF, Juul N, Marshall SB, Benedict B, Marshall LF. Neurological deterioration as a potential alternative endpoint in human clinical trials of experimental pharmacological agents for treatment of severe traumatic brain injuries. Executive Committee of the International Selfotel Trial. Neurosurgery. 1998 Dec;43(6):1369-72; discussion 1372-4.

  PMID: 9848851 BACKGROUND

• Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010 Oct;41(10):2391-5. doi: 10.1161/STROKEAHA.110.589275. Epub 2010 Aug 26.

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• Stocchetti N, Taccone FS, Citerio G, Pepe PE, Le Roux PD, Oddo M, Polderman KH, Stevens RD, Barsan W, Maas AI, Meyfroidt G, Bell MJ, Silbergleit R, Vespa PM, Faden AI, Helbok R, Tisherman S, Zanier ER, Valenzuela T, Wendon J, Menon DK, Vincent JL. Neuroprotection in acute brain injury: an up-to-date review. Crit Care. 2015 Apr 21;19(1):186. doi: 10.1186/s13054-015-0887-8.

  PMID: 25896893 BACKGROUND

• Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007 Jul;99(1):4-9. doi: 10.1093/bja/aem131.

  PMID: 17573392 BACKGROUND

• Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007 Jan;87(1):315-424. doi: 10.1152/physrev.00029.2006.

  PMID: 17237348 BACKGROUND

• Garry PS, Ezra M, Rowland MJ, Westbrook J, Pattinson KT. The role of the nitric oxide pathway in brain injury and its treatment--from bench to bedside. Exp Neurol. 2015 Jan;263:235-43. doi: 10.1016/j.expneurol.2014.10.017. Epub 2014 Oct 29.

  PMID: 25447937 BACKGROUND

• Toda N, Ayajiki K, Okamura T. Cerebral blood flow regulation by nitric oxide: recent advances. Pharmacol Rev. 2009 Mar;61(1):62-97. doi: 10.1124/pr.108.000547. Epub 2009 Mar 16.

  PMID: 19293146 BACKGROUND

• Cherian L, Goodman JC, Robertson CS. Brain nitric oxide changes after controlled cortical impact injury in rats. J Neurophysiol. 2000 Apr;83(4):2171-8. doi: 10.1152/jn.2000.83.4.2171.

  PMID: 10758126 BACKGROUND

• Sehba FA, Schwartz AY, Chereshnev I, Bederson JB. Acute decrease in cerebral nitric oxide levels after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2000 Mar;20(3):604-11. doi: 10.1097/00004647-200003000-00018.

  PMID: 10724124 BACKGROUND

• Sehba FA, Bederson JB. Nitric oxide in early brain injury after subarachnoid hemorrhage. Acta Neurochir Suppl. 2011;110(Pt 1):99-103. doi: 10.1007/978-3-7091-0353-1_18.

  PMID: 21116923 BACKGROUND

• Sobey CG, Faraci FM. Subarachnoid haemorrhage: what happens to the cerebral arteries? Clin Exp Pharmacol Physiol. 1998 Nov;25(11):867-76. doi: 10.1111/j.1440-1681.1998.tb02337.x.

  PMID: 9807657 BACKGROUND

• Sehba FA, Chereshnev I, Maayani S, Friedrich V Jr, Bederson JB. Nitric oxide synthase in acute alteration of nitric oxide levels after subarachnoid hemorrhage. Neurosurgery. 2004 Sep;55(3):671-7; discussion 677-8. doi: 10.1227/01.neu.0000134557.82423.b2.

  PMID: 15335435 BACKGROUND

• Hino A, Tokuyama Y, Weir B, Takeda J, Yano H, Bell GI, Macdonald RL. Changes in endothelial nitric oxide synthase mRNA during vasospasm after subarachnoid hemorrhage in monkeys. Neurosurgery. 1996 Sep;39(3):562-7; discussion 567-8. doi: 10.1097/00006123-199609000-00026.

  PMID: 8875487 BACKGROUND

• Jung CS, Oldfield EH, Harvey-White J, Espey MG, Zimmermann M, Seifert V, Pluta RM. Association of an endogenous inhibitor of nitric oxide synthase with cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg. 2007 Nov;107(5):945-50. doi: 10.3171/JNS-07/11/0945.

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• Pluta RM. Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH. Acta Neurochir Suppl. 2008;104:139-47. doi: 10.1007/978-3-211-75718-5_28.

  PMID: 18456999 BACKGROUND

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  PMID: 19726713 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood (whole blood, serum, plasma, and red blood cells)

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Cerebral Hemorrhage; Brain Injuries, Traumatic; Brain Injuries

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Anton Lund, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 28, 2021
• First Posted: July 6, 2021
• Study Start: August 18, 2021
• Primary Completion: April 30, 2024
• Study Completion: September 1, 2025
• Last Updated: November 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The approved study protocol will be available upon request until publication of the study results.
• Access Criteria: Valid reason and contact with author.

Locations

DK (1)