MicroRNA Diagnostics in Subarachnoid Hemorrhage

Subarachnoid Hemorrhage Clinical Trial

Official title:

MicroRNA Expression in Cerebrospinal Fluid From Patients Suffering Subarachnoid Hemorrhage With and Without Delayed Cerebral Ischemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01791257
• Other study ID #: MicroRNA in SAH
• Status: Completed
• Phase: N/A
• First received: February 12, 2013
• Last updated: April 7, 2014
• Start date: February 2013
• Est. completion date: January 2014

Study information

• Verified date: April 2014
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Danish Healthcare SystemDenmark: DatatilsynetDenmark: Danish Regional Scientific Ethics Committee of the Capital Region
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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."

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hemorrhage
• Subarachnoid Hemorrhage

Locations

Country	Name	City	State
Denmark	Bispebjerg Hospital	Copenhagen
Denmark	Rigshospitalet	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Bispebjerg Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delayed Cerebral Ischemia - Clean groups	Delayed Cerebral Ischemia as defined by Vergouwen et al in Stroke 2010;41(10):2391-2395.; We found confirmation/exclusion of DCI difficult in a few patients. To minimize error, two clinicians reviewed all clinical, biochemical and radiological data, obtained 3 weeks from ictus, and independently assessed if any clinical deterioration fulfilled the criteria of delayed cerebral ischemia. Furthermore, included patients were categorized as "definitely DCI", "probably DCI", "probably not DCI" or "definitely not DCI".; Therefore we decided to modify our primary outcome measure in this case-control study to compare "definitely DCI" vs. "definitely not DCI".	21 days	No
Secondary	Early brain injury: Comparison of microRNA profiles with clinical neurology following occlusion of the aneurysm	Comparison of 667 specific microRNAs in CSF at day 5 after ictus between two groups of SAH-patients depending on their clinical neurology at the first wake-up call following occlusion of the aneurysm: GCS 3-12 and/or (paresis (degree 4) of at least one extremity or aphasia); GCS 13-15 and no or only small and mild focal deficit	Assessed at the first wake-up call following clip or coil	No
Secondary	Association of microRNA-profile with 3 month outcome	Comparison of 667 specific microRNAs in CSF at day 5 after ictus between two groups of SAH-patients depending on their mRS at 3 month follow-up in groups: mRS = 3-6; mRS = 0-2	Follow up examination at 3 month or as close to this	No
Secondary	Delayed Cerebral Ischemia as defined by Vergouwen et al in Stroke 2010;41(10):2391-2395. Large groups.	Delayed Cerebral Ischemia as defined by Vergouwen et al in Stroke 2010;41(10):2391-2395.; In contrast to our primary outcome measure, these groups will include patients where DCI was difficult to exclude or confirm.; Thereby we wish to compare "definitely DCI" and "probably DCI" vs. "probably not DCI" and "definetly not DCI". This would enable comparison between larger groups though less clean.	21 days following ictus	No
Secondary	Relation of microRNA profile to cerebral infarction as defined by Vergouwen et al in Stroke 2010;41(10):2391-2395.	The presence of cerebral infarction on CT or MR scan of the brain within 6 weeks after SAH, or on the latest CT or MR scan made before death within 6 weeks, or proven at autopsy, not present on the CT or MR scan between 24 and 48 hours after early aneurysm occlusion, and not attributable to other causes such as surgical clipping or endovascular treatment. Hypodensities on CT imaging resulting from ventricular catheter or intraparenchymal hematoma should not be regarded as cerebral infarctions from DCI.	Following a blinded description of CT-scans	No
Secondary	Relation of microRNA profile to the regional area of cerebral injury	As microRNAs seem to be specific for different areas of the brain our screening might tell us which area has sustained injury and which has not. This study will not include two groups as the secondary outcome measures above.	Following a blinded description of CT-scans	No