Traumatic Brain InjuryNCT00419874
Characteristics of Blood- Brain Barrier Permeability in Neurological Patients
An observational study of Traumatic Brain Injury and Cerebral Infarction, run by Soroka University Medical Center at 1 site in Israel.
Trial summary
The main goal of the present study is to challenge the hypothesis that blood- brain barrier disruption following brain injury increases the risk for long-term disability, development of brain dysfunction, epileptic seizures and neuroanatomical alterations. Read more about this study
- Who is it for?
- Ages 16 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Traumatic Brain Injury, Cerebral Infarction, Cerebral Hemorrhage
- How many people
- 100 participants
- Where
- 1 siteIsrael
- Study dates
- Start not givento not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 75 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- One week following:
- Traumatic Brain Injury
- Cerebro- Vascular Accident
- Subsequent brain CT showed cerebral cortex injury.
Who cannot join
- A known ailment of the central nervous system.
- Use of medications or illicit drugs that significantly affect the central nervous system.
- tourist or temporary residents not available for follow-up.
- For MRI examinations: heart pacemaker, metal implants, or metal shrapnel.
Trial locations and contacts
1 site in 1 country.
Alon Friedman, MD/PhD contact
Israel1 site, 1 recruiting
- Recruiting
Soroka University Medical Center
Beersheba
Alon Friedman, MD/PhD, alonf@bgu.ac.il
Alon Friedman, MD/PhD
About this study
Official title: Blood- Brain Barrier Permeability in Neurological Patients: Anatomical, Neurophysiological, and Clinical Characteristics
The main goal of the present study is to challenge the hypothesis that blood- brain barrier disruption following brain injury increases the risk for long-term disability, development of brain dysfunction, epileptic seizures and neuroanatomical alterations.
Read the detailed description
Traumatic brain injury (TBI) is one of the most common traumatic events, occurring in approximately 200 per 100,000, and is a known risk factor for later development of epileptic seizures. This occurs in up to 17% of TBI patients, and accounts for approximately 20% of symptomatic epilepsies (Annegers, JF. et al, 1998). Typically, post-traumatic epilepsy (PTE) develops or several weeks but even years after the event. PTE is often chronic and poorly controlled pharmacologically. Although several factors have been attributed to an increased risk of developing PTE (e.g. severity of trauma, type of brain injury, time to the appearance of first seizure), the mechanisms underlying it remain unknown. Similar to TBI, ischemic injuries, most frequently occurring in the elderly population are the main cause of new onset epilepsy in this age group. It is still not known what are the risk factors and mechanisms underlying post-ischemic epilepsy.
Under normal conditions the central nervous system is protected by the operation of the blood- brain barrier (BBB). Following brain injury (either traumatic or ischemic) the BBB is known to disrupt, leading to focal edema and altered extracellular composition. We have recently established methods for quantitative evaluation of the integrity of the BBB using magnetic resonance imaging (MRI) brain scans. Using these methods we are able to identify BBB disruption in patients suffering from various pathologies (Tomkins, O. et al. 2001; Avivi, E. et al. 2004). Such altered permeability may last up to years following the acute event and was found to correlate to areas of abnormal neurological function (Korn, A. et al. 2005)
In recent work using an animal model, we have shown that following focal disruption of the BBB a focus of epileptiform activity is generated within several days. Such pathological activity remains for several weeks, long after the BBB has retained its former function (Seiffert, E. et al. 2004; Iven, S. et al. 2006). Furthermore, this condition may later lead to anatomical alterations as seen by brain MRI scans, as well as in histological sections. Such animals further suffer from functional deterioration and neuronal degeneration in the disrupted region (Tomkins, O. et al. 2006).
In this work we will test the hypothesis that BBB disruption following brain injury increases the risk for long-term disability, development of brain dysfunction, epileptic seizures and neuroanatomical alterations. For that we will combine a prospective and retrospective study in patients following cerebral cortical injury (traumatic, hemorrhagic or ischemic). Clinical, functional and anatomical measures will be obtained in addition to BBB permeability measures.
- Keywords
- Blood-brain barrier, Post traumatic epilepsy, Seizures
- Medical subject headings
- Brain Injuries, Traumatic, Cerebral Infarction, Cerebral Hemorrhage, Epilepsy, Post-Traumatic, Seizures
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2007 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Defined population
- Time perspective
- Other
- Enrolment
- 100 participants
Sponsor and investigators
- Lead sponsor
- Soroka University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Alon Friedman, MD/PhD, Principal investigator, Soroka University Medical CenterIlan Shelef, MD, Principal investigator, Soroka University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00419874
- Sponsor's protocol ID
- SOR444206CTIL
- Status last verified
- Nov 2006
- First submitted
- 7 Jan 2007
- Last updated
- 9 Jan 2007
- Results posted
- No
Publications
Tomkins O, Friedman O, Ivens S, Reiffurth C, Major S, Dreier JP, Heinemann U, Friedman A. Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex. Neurobiol Dis. 2007 Feb;25(2):367-77. doi: 10.1016/j.nbd.2006.10.006. Epub 2006 Dec 22.
PubMed 17188501Ivens S, Kaufer D, Flores LP, Bechmann I, Zumsteg D, Tomkins O, Seiffert E, Heinemann U, Friedman A. TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. Brain. 2007 Feb;130(Pt 2):535-47. doi: 10.1093/brain/awl317. Epub 2006 Nov 21.
PubMed 17121744Dreier JP, Jurkat-Rott K, Petzold GC, Tomkins O, Klingebiel R, Kopp UA, Lehmann-Horn F, Friedman A, Dichgans M. Opening of the blood-brain barrier preceding cortical edema in a severe attack of FHM type II. Neurology. 2005 Jun 28;64(12):2145-7. doi: 10.1212/01.WNL.0000176298.63840.99.
PubMed 15985592Seiffert E, Dreier JP, Ivens S, Bechmann I, Tomkins O, Heinemann U, Friedman A. Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci. 2004 Sep 8;24(36):7829-36. doi: 10.1523/JNEUROSCI.1751-04.2004.
PubMed 15356194
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood- Brain Barrier Permeability in Neurological Patients: Anatomical, Neurophysiological, and Clinical Characteristics
- ClinicalTrials.gov ID
- NCT00419874
- Acronym / sponsor ID
- SOR444206CTIL
- Keywords
- Blood-brain barrier, Post traumatic epilepsy, Seizures
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants
- Lead sponsor
- Soroka University Medical CenterUniversity, hospital or other
- First posted
- 9 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main goal of the present study is to challenge the hypothesis that blood- brain barrier disruption following brain injury increases the risk for long-term disability, development of brain dysfunction, epileptic seizures and neuroanatomical alterations.
Detailed description
Traumatic brain injury (TBI) is one of the most common traumatic events, occurring in approximately 200 per 100,000, and is a known risk factor for later development of epileptic seizures. This occurs in up to 17% of TBI patients, and accounts for approximately 20% of symptomatic epilepsies (Annegers, JF. et al, 1998). Typically, post-traumatic epilepsy (PTE) develops or several weeks but even years after the event. PTE is often chronic and poorly controlled pharmacologically. Although several factors have been attributed to an increased risk of developing PTE (e.g. severity of trauma, type of brain injury, time to the appearance of first seizure), the mechanisms underlying it remain unknown. Similar to TBI, ischemic injuries, most frequently occurring in the elderly population are the main cause of new onset epilepsy in this age group. It is still not known what are the risk factors and mechanisms underlying post-ischemic epilepsy.
Under normal conditions the central nervous system is protected by the operation of the blood- brain barrier (BBB). Following brain injury (either traumatic or ischemic) the BBB is known to disrupt, leading to focal edema and altered extracellular composition. We have recently established methods for quantitative evaluation of the integrity of the BBB using magnetic resonance imaging (MRI) brain scans. Using these methods we are able to identify BBB disruption in patients suffering from various pathologies (Tomkins, O. et al. 2001; Avivi, E. et al. 2004). Such altered permeability may last up to years following the acute event and was found to correlate to areas of abnormal neurological function (Korn, A. et al. 2005)
In recent work using an animal model, we have shown that following focal disruption of the BBB a focus of epileptiform activity is generated within several days. Such pathological activity remains for several weeks, long after the BBB has retained its former function (Seiffert, E. et al. 2004; Iven, S. et al. 2006). Furthermore, this condition may later lead to anatomical alterations as seen by brain MRI scans, as well as in histological sections. Such animals further suffer from functional deterioration and neuronal degeneration in the disrupted region (Tomkins, O. et al. 2006).
In this work we will test the hypothesis that BBB disruption following brain injury increases the risk for long-term disability, development of brain dysfunction, epileptic seizures and neuroanatomical alterations. For that we will combine a prospective and retrospective study in patients following cerebral cortical injury (traumatic, hemorrhagic or ischemic). Clinical, functional and anatomical measures will be obtained in addition to BBB permeability measures.
Study design
- Observational model
- Defined population
- Time perspective
- Other
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- One week following:
- Subsequent brain CT showed cerebral cortex injury.
Key exclusion criteria (4 listed)
- A known ailment of the central nervous system.
- Use of medications or illicit drugs that significantly affect the central nervous system.
- tourist or temporary residents not available for follow-up.
- For MRI examinations: heart pacemaker, metal implants, or metal shrapnel.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2007.
- Background: PubMed 17188501Tomkins O, Friedman O, Ivens S, Reiffurth C, Major S, Dreier JP, Heinemann U, Friedman A. Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex. Neurobiol Dis. 2007 Feb;25(2):367-77. doi: 10.1016/j.nbd.2006.10.006. Epub 2006 Dec 22.
- Background: PubMed 17121744Ivens S, Kaufer D, Flores LP, Bechmann I, Zumsteg D, Tomkins O, Seiffert E, Heinemann U, Friedman A. TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. Brain. 2007 Feb;130(Pt 2):535-47. doi: 10.1093/brain/awl317. Epub 2006 Nov 21.
- Background: PubMed 15985592Dreier JP, Jurkat-Rott K, Petzold GC, Tomkins O, Klingebiel R, Kopp UA, Lehmann-Horn F, Friedman A, Dichgans M. Opening of the blood-brain barrier preceding cortical edema in a severe attack of FHM type II. Neurology. 2005 Jun 28;64(12):2145-7. doi: 10.1212/01.WNL.0000176298.63840.99.
- Background: PubMed 15356194Seiffert E, Dreier JP, Ivens S, Bechmann I, Tomkins O, Heinemann U, Friedman A. Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci. 2004 Sep 8;24(36):7829-36. doi: 10.1523/JNEUROSCI.1751-04.2004.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alon Friedman, MD/PhD contact
Alon Friedman, MD/PhD principal investigator
Soroka University Medical Center
Ilan Shelef, MD principal investigator
Soroka University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Traumatic Brain Injury and Cerebral Infarction, run by Soroka University Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Jan 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alon Friedman, MD/PhD (alonf@bgu.ac.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00419874, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2007.