MicroRNA Diagnostics in Subarachnoid Hemorrhage 2

The purpose of this study is to validate results from a related trial (NCT01791257) and to compare the profile of microRNA in blood from patients suffering subarachnoid hemorrhage with and without systemic complications.

Study Overview

• Status: Completed
• Conditions: Systemic Inflammatory Response Syndrome; Subarachnoid Hemorrhage; Acute Lung Injury; Delayed Cerebral Ischemia; Cardiac Dysfunction

Detailed Description

In this study of patients suffering an aneurysmal subarachnoid hemorrhage (SAH) we would like to validate former results from CSF studies through microRNA profiling investigate the pathophysiological mechanisms that lead to systemic complications such as cardiac dysfunction, acute lung injury (ALI) and systemic inflammatory response syndrome(SIRS).

We will accomplish this through analyzing the profile of microRNA expression in blood and cerebrospinal fluid from SAH patients.

Validation:

As in our earlier study we wish to compare the expression of 20 specific microRNA between 12 patients developing DCI (group 1) and 12 patients without DCI (group 2) in cerebrospinal fluid drawn on day 5 after ictus. In addition, some of the patients will have established invasive neuromonitoring including microdialysis in which we will study changes of certain microRNAs.

DCI as defined by Vergouwen et al in Stroke 2010;41(10):2391-2395:

"The occurrence of focal neurological impairment (such as hemiparesis, aphasia, apraxia, hemianopia, or neglect), or a decrease of at least 2 points on the Glasgow Coma Scale (either on the total score or on one of its individual components [eye, motor on either side, verbal]). This should last for at least 1 hour, is not apparent immediately after aneurysm occlusion, and cannot be attributed to other causes by means of clinical assessment, CT or MRI scanning of the brain, and appropriate laboratory studies."

Systemic complications:

Furthermore, we wish to compare the expression of 754 specific microRNA in blood drawn on day 3 after ictus between patients with ALI (as described Kahn et al, Crit Care Med. 2006; 34: 196-202) and patients without ALI. Of at least 36 patients expected to be included 12 should statistically develop ALI according to the referred definition.

Additionally, we wish to compare the expression of 754 specific microRNA between 12 patients developing DCI (group 1) and 12 patients without DCI (group 2) in blood drawn on day 3 after ictus.

Moreover, we wish to compare the expression of 754 specific microRNA in blood between 36 patients (group 1-3) to that of healthy controls. The specific microRNAs of interest in which the expression in blood between patients with systemic complication are analyzed daily to investigate the dynamic changes in expression and compared to the clinical course.

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet

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: Probability Sample

Study Population

Group 1-2: Patients admitted to Neurointensive Department in Rigshospitalet with SAH treated with external ventricular drain.

Group 3: Patients admitted to Neurointensive Department in Rigshospitalet with SAH treated without external ventricular drain.

Group 4: Healthy blood donors

Description

Inclusion Criteria Group 1-3:

• Uncertainty < 24 times on time of ictus

Inclusion Criteria Group 1-2:

• Patients admitted to Neurointensive Department in Rigshospitalet with aneurysmal SAH treated with external ventricular drain.

Inclusion Criteria Group 3:

• Patients admitted to Neurointensive Department in Rigshospitalet with aneurysmal SAH treated without external ventricular drain.

Exclusion Criteria Group 1-3:

• Transfer to other hospital within 5 days of admission

Study Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
SAH with DCI; After 21 days from ictus the patients with subarachnoid hemorrhage are stratified to group 1 or 2 depending on their development of delayed cerebral ischemia.
SAH without DCI; After 21 days from ictus the patients with subarachnoid hemorrhage are stratified to group 1 or 2 depending on their development of delayed cerebral ischemia.
SAH good grade; SAH without external ventricular drainage
Healthy controls; Blood sample in healthy donors registered in the National Donor Registry.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delayed Cerebral Ischemia	Delayed Cerebral Ischemia as defined by Vergouwen et al[1]. In our earlier study we found the clinical condition DCI somehow subjective which is why we added the following two primary outcome measures. Comparing microRNA profiles between groups with or without.	21 days
Delayed Cerebral Ischemia and Cerebral infarction	as defined by Vergouwen et al [1]. Comparing microRNA profiles between groups with or without.	21 days
Delayed Cerebral infarction	as defined by Vergouwen et al [1]. Comparing microRNA profiles between groups with or without.	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Lung Injury	as defined by Kahn et al[2]. Comparing microRNA profiles between groups with or without	21 days
Cardiac Dysfunction	Evaluated by transthoracic echocardiography Comparing microRNA profiles between groups with or without	21 days
Systemic Inflammatory Response Syndrome	Evaluated through daily vital signs and biochemistry Comparing microRNA profiles between groups with or without	21 days
Early Brain Injury	Early Brain injury = GCS 3-12 and/or paresis (degree 4) of at least one extremity or aphasia No Early Brain injury = GCS 13-15 and no or only small and mild focal deficit Comparing microRNA profiles between groups with or without	Clinical evaluation 24-72 hours after ictus. (Wake-up call if sedated)

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Study Director: Kirsten Møller, Prof, Neurointensive Care Unit, The Neuroscience Center, Rigshospitalet

Publications and helpful links

General Publications

• Matzen JS, Krogh CL, Forman JL, Garred P, Møller K, Bache S. Lectin complement pathway initiators after subarachnoid hemorrhage - an observational study. J Neuroinflammation. 2020 Nov 12;17(1):338. doi: 10.1186/s12974-020-01979-y.

Helpful Links

• [1] Vergouwen et al in Stroke 2010;41(10):2391-2395.
• [2] Kahn et al, Crit Care Med, Vol. 34, No.1 2006

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: October 28, 2014
• First Submitted That Met QC Criteria: December 15, 2014
• First Posted (Estimate): December 19, 2014

Study Record Updates

• Last Update Posted (Estimate): May 27, 2015
• Last Update Submitted That Met QC Criteria: May 25, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Cerebrospinal fluid; MicroRNA
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Lung Diseases; Inflammation; Wounds and Injuries; Shock; Infarction; Stroke; Brain Infarction; Intracranial Hemorrhages; Thoracic Injuries; Brain Ischemia; Ischemia; Hemorrhage; Cerebral Infarction; Subarachnoid Hemorrhage; Acute Lung Injury; Lung Injury; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: H-6-2014-073

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