Clinical trial NCT01791257: MicroRNA Diagnostics in Subarachnoid Hemorrhage
Official title: MicroRNA Expression in Cerebrospinal Fluid From Patients Suffering Subarachnoid Hemorrhage With and Without Delayed Cerebral Ischemia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Subarachnoid Hemorrhage
Keywords: delayed
cerebral
ischemia
microrna
cerebrospinal fluid
subarachnoid
hemorrhage
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Bispebjerg Hospital
First posted: 2013-02-13
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Group 1+2: Patients admitted to Neurointensive Department in Rigshospitalet. Group 3: Patients undergoing spinal anesthesia for orthopedic surgery in Bispebjerg Hospital.

Brief summary: The purpose of this study is to compare the profile of microRNA in cerebrospinal fluid from patients suffering subarachnoid hemorrhage with and without delayed cerebral ischemia.

Detailed description: In this study of patients suffering an aneurysmal subarachnoid hemorrhage (SAH) we would like to investigate the pathophysiological mechanisms that lead to the phenomenon delayed cerebral ischemia (DCI).

We will accomplish this through analyzing the profile of microRNA expression in the cerebrospinal fluid of SAH patients treated with extraventricular drainage.

At first we wish to compare the expression of 376 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.

Secondly specific microRNAs of interest in which the expression differs between group 1 and 2 are analyzed daily to investigate the dynamic changes in expression and compared to the clinical course.

Should we find no differently expressed specific microRNAs we will compare the expression of microRNA in group 1+2 with group 3.

In addition, some of the patients as part of another clinical trial (NCT01447095

) will have established invasive neuromonitoring including microdialysis. It is our intention to develop a method for analyzing microRNA in this microdialysate.

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."

Eligibility criteria: Inclusion Criteria:

* Patient admitted to the neurointensive care unit with aneurismal subarachnoid hemorrhage
* External ventricular drainage with 5 days of ictus
* Age \> 18 years

Exclusion Criteria:

* Glasgow Coma Score (GCS) continuously \< 7 during the first 5 days following ictus
* A known and proven complication (rebleeding, clip/coil complication, cardiopulmonal complication requiring full sedation, ventriculitis e.g.) leads to a GCS \< 7 thereby preventing the detection of DCI.

Primary outcomes:
measure: Delayed Cerebral Ischemia - Clean groups
timeFrame: 21 days
Secondary outcomes:
measure: Early brain injury: Comparison of microRNA profiles with clinical neurology following occlusion of the aneurysm
timeFrame: Assessed at the first wake-up call following clip or coil
measure: Association of microRNA-profile with 3 month outcome
timeFrame: Follow up examination at 3 month or as close to this
measure: Delayed Cerebral Ischemia as defined by Vergouwen et al in Stroke 2010;41(10):2391-2395. Large groups.
timeFrame: 21 days following ictus
measure: Relation of microRNA profile to cerebral infarction as defined by Vergouwen et al in Stroke 2010;41(10):2391-2395.
timeFrame: Following a blinded description of CT-scans
measure: Relation of microRNA profile to the regional area of cerebral injury
timeFrame: Following a blinded description of CT-scans
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
Study officials:
affiliation: Rigshopsitalet, Denmark
name: Søren B Larsen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Kirsten Møller, DMSci
role: STUDY_CHAIR
References:
citation: Matzen JS, Krogh CL, Forman JL, Garred P, Moller 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.
citation: Bache S, Rasmussen R, Rossing M, Laigaard FP, Nielsen FC, Moller K. MicroRNA Changes in Cerebrospinal Fluid After Subarachnoid Hemorrhage. Stroke. 2017 Sep;48(9):2391-2398. doi: 10.1161/STROKEAHA.117.017804. Epub 2017 Aug 2.