MicroRNA Diagnostics in Subarachnoid Hemorrhage

April 7, 2014 updated by: Søren Bache Larsen, MD, Rigshospitalet, Denmark

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

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.

Study Overview

Status

Completed

Conditions

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."

Study Type

Observational

Enrollment (Actual)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2400
        • Bispebjerg Hospital
      • Copenhagen, Denmark, 1302
        • Rigshospitalet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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.
Neurological healthy controls
12 patients (ASA 1) undergoing spinal anesthesia for orthopedic surgery have 2 ml of cerebrospinal fluid drawn preceding injection of local analgetic.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Delayed Cerebral Ischemia - Clean groups
Time Frame: 21 days

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Early brain injury: Comparison of microRNA profiles with clinical neurology following occlusion of the aneurysm
Time Frame: Assessed at the first wake-up call following clip or coil

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:

  1. GCS 3-12 and/or (paresis (degree 4) of at least one extremity or aphasia)
  2. GCS 13-15 and no or only small and mild focal deficit
Assessed at the first wake-up call following clip or coil
Association of microRNA-profile with 3 month outcome
Time Frame: Follow up examination at 3 month or as close to this

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:

  1. mRS = 3-6
  2. mRS = 0-2
Follow up examination at 3 month or as close to this
Delayed Cerebral Ischemia as defined by Vergouwen et al in Stroke 2010;41(10):2391-2395. Large groups.
Time Frame: 21 days following ictus

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
Relation of microRNA profile to cerebral infarction as defined by Vergouwen et al in Stroke 2010;41(10):2391-2395.
Time Frame: Following a blinded description of CT-scans
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
Relation of microRNA profile to the regional area of cerebral injury
Time Frame: Following a blinded description of CT-scans
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rigshospitalet, Denmark

Collaborators

Bispebjerg Hospital

Investigators

  • Principal Investigator: Søren B Larsen, MD, Rigshopsitalet, Denmark
  • Study Chair: Kirsten Møller, DMSci, Rigshospitalet, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (Actual)

January 1, 2014

Study Completion (Actual)

January 1, 2014

Study Registration Dates

First Submitted

February 12, 2013

First Submitted That Met QC Criteria

February 12, 2013

First Posted (Estimate)

February 13, 2013

Study Record Updates

Last Update Posted (Estimate)

April 8, 2014

Last Update Submitted That Met QC Criteria

April 7, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MicroRNA in SAH

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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