Blood-Brain Barrier PermeabilityNCT02033291
Blood-brain Barrier Quantification in Cerebral Small Vessel Disease
An observational study of Blood-Brain Barrier Permeability and Cerebral Small Vessel Disease, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Cerebral small vessel disease (cSVD) encompasses all pathological processes that affect the small vessels of the brain. On brain-MRI cSVD is characterized by structural brain abnormalities such as white matter lesions (WMLs). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Blood-Brain Barrier Permeability, Cerebral Small Vessel Disease, Cerebral Hemorrhage
- What is being tested?
- Dynamic contrast enhanced Brain MRI
- Type of treatment
- Surgery or procedure
- How many people
- 17 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2014to Oct 2016
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: General: * Age >18 years old * The condition of the patient must be well enough to allow participation in the study, which is decided in consultation with the treating physician. cSVD patients: - patients who present with a transient ischemic attack (TIA) and cSVD related abnormalities on brain MRI. MRI abnormalities include extended white matter lesions, (asymptomatic) lacunar infarcts, microbleeds and enlarged Virchow-Robin spaces. The patients are eligible when the first DCE-MRI scan can be performed 8-12 weeks after the TIA to avoid the acute phase, and the second MRI-scan within four weeks after the first. Cortical stroke or primary intracerebral hemorrhage patients: - patients who have a clear clinical presentation of either cortical stroke or primary intracerebral hemorrhage confirmed on brain CT. The patients are eligible when the DCE-MRI scans can be performed within 0-6 weeks of the vascular event and on two subsequent days.
Who may be able to join
- All subjects:
- Age >18 years old
- The condition of the patient must be well enough to allow participation in the study, which is decided in consultation with the treating physician.
- cSVD patients: - patients who present with a transient ischemic attack (TIA) and cSVD related abnormalities on brain MRI. TIA patients are defined as patients with stroke like symptoms that last no longer than 24 hours. MRI abnormalities include extended white matter lesions, (asymptomatic) lacunar infarcts, microbleeds and enlarged Virchow-Robin spaces. The patients are eligible when the first DCE-MRI scan can be performed 8-12 weeks after the TIA to avoid the acute phase, and the second MRI-scan within four weeks after the first.
- Cortical stroke or primary intracerebral hemorrhage patients:
- patients who have a clear clinical presentation of either cortical stroke or primary intracerebral hemorrhage confirmed on brain CT. The patients are eligible when the DCE-MRI scans can be performed within 0-6 weeks of the vascular event and on two subsequent days as the vascular permeability may change significantly on the timescale of weeks.
Who cannot join
- All subjects:
- History of cerebrovascular disease (e.g. ischemic/hemorrhagic stroke)
- History of other diseases of the central nervous system (e.g. epilepsy, brain tumor, multiple sclerosis)
- Contra-indications for MRI examination: e.g. pacemaker; neurostimulator; medication pump; cochlear or hearing implant; tattoos or other items that cannot be removed and include metal parts (for instance from operations in the past); metal splinter in the eye; pregnancy and claustrophobia; brain vessel clamps; denture, which contains magnets.
- Contra-indication for MRI contrast agent: e.g. strong suspicion for impaired kidney function (GFR<30ml/min), previous allergic reaction to contrast agent, dialysis patients
- Psychiatric co-morbidity and inability to perform the (DCE-)MRI scans.
Show all 9Show fewer
- cSVD patients
- Patients with a potential cardioembolic source (e.g. atrial fibrillation)
- Stenosis of ≥50% of one or both internal carotid arteries
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, Limburg, 5800
About this study
Official title: Blood-Brain Barrier Permeability Quantification in Cerebral Small Vessel Disease -- Reproducibility of Dynamic Contrast-enhanced MRI
Cerebral small vessel disease (cSVD) encompasses all pathological processes that affect the small vessels of the brain. On brain-MRI cSVD is characterized by structural brain abnormalities such as white matter lesions (WMLs). Clinically, cSVD is related to acute syndromes as lacunar stroke but also to more chronic health problems such as cognitive decline. Recent literature suggests that a disrupted blood brain barrier (BBB), leading to elevated BBB permeability, may play a pivotal role in the aetiology of cSVD and lacunar stroke. The BBB is a complex system of neuronal, glial and vascular cells which main function is to shield the brain from toxic components and regulate the homeostasis. Elucidating the role of the BBB may have far reaching consequences for the treatment of cSVD patients and the reduction of recurrence rate of the disease. This could lead to a better quality of life among cSVD patients and reduce the economic burden on society. Currently the exact contribution and extent of a possibly defective BBB in cSVD remains largely unclear, due to the lack of a reliable method to accurately quantify the BBB permeability in cSVD patients. As a result, the current treatment consists of treating the cardiovascular risk factors, often with poor results.
Quantification of the BBB permeability provides an objective measure of the integrity of the BBB and as such aids the study of the role of the BBB. The aim of this study is to realize a clinically applicable MRI-method to quantify the BBB permeability. Moreover, the method can be used to study the involvement of BBB disruption in other neuropathologies including Alzheimer's disease, vascular dementia, hypertension and diabetes.
Read more
Primary Study Objective:
To realize a clinically applicable quantification of BBB permeability using DCE-MRI by determining the reproducibility of the DCE-MRI method
Secondary Study Objective:
To achieve the shortest scan duration without compromising the reliability of the BBB permeability quantification.
Hypotheses:
- Using an optimized DCE-MRI method to quantify the BBB permeability, the BBB permeability can be reliably determined in cSVD patients.
- The scan duration can be shortened without compromising the reliability of the BBB permeability quantification.
- Conditions
- Blood-Brain Barrier Permeability, Cerebral Small Vessel Disease, Cerebral Hemorrhage, Cortical Stroke
- Being tested
- Dynamic contrast enhanced Brain MRI
- Keywords
- Cerebral Small Vessel Disease, Blood-Brain Barrier permeability, Dynamic contrast enhanced Magnetic Resonance Imaging, Pharmacokinetic modeling, Reproducibility
- Medical subject headings
- Cerebral Small Vessel Diseases, Cerebral Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dynamic contrast enhanced Brain MRIProcedure or surgery
DCE-MRI is used to quantify the BBB permeability
| Study group | Role | What they receive |
|---|---|---|
| Cortical stroke or primary intracerebral hemorrhage patients: | patients who have a clear clinical presentation of either cortical stroke or primary intracerebral hemorrhage confirmed on brain CT. The patients are eligible when the DCE-MRI scans can be performed within 0-6 weeks of the vascular event and on two subsequent days as the vascular permeability may change significantly on the timescale of weeks. Receives: Procedure: Dynamic contrast enhanced Brain MRI | |
| cSVD patients | patients who present with a transient ischemic attack (TIA) and cSVD related abnormalities on brain MRI. TIA patients are defined as patients with stroke like symptoms that last no longer than 24 hours. MRI abnormalities include extended white matter lesions, (asymptomatic) lacunar infarcts, microbleeds and enlarged Virchow-Robin spaces. The patients are eligible when the first DCE-MRI scan can be performed 8-12 weeks after the TIA to avoid the acute phase, and the second MRI-scan within four weeks after the first. Receives: Procedure: Dynamic contrast enhanced Brain MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
pharmacokinetic parameter values Ki and vb
Outcome measures of both days are used to determine the reproducibility of the DCE-MRI method.
Measured: day 1 & day 2. Day 2 is min. 24 hours max. 4 weeks after day 1.
Secondary outcomes (1)
pharmacokinetic parameter values: Ki and vb for the retrospectively shortened dynamic scans
The pharmacokinetic parameters are evaluated as a function of scan duration to obtain the shortest scan duration without compromising the reliability of the BBB permeability quantification.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completionDec 2015
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Blood-Brain Barrier PermeabilityStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cecile RLPN Jeukens, PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02033291
- Sponsor's protocol ID
- 13-2-036
- Status last verified
- Oct 2016
- First submitted
- 8 Jan 2014
- Last updated
- 24 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood-Brain Barrier Permeability Quantification in Cerebral Small Vessel Disease -- Reproducibility of Dynamic Contrast-enhanced MRI
- ClinicalTrials.gov ID
- NCT02033291
- Acronym / sponsor ID
- 13-2-036
- Conditions
- Blood-Brain Barrier Permeability, Cerebral Small Vessel Disease, Cerebral Hemorrhage, Cortical Stroke
- Keywords
- Cerebral Small Vessel Disease, Blood-Brain Barrier permeability, Dynamic contrast enhanced Magnetic Resonance Imaging, Pharmacokinetic modeling, Reproducibility
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 10 Jan 2014 (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.
Cerebral small vessel disease (cSVD) encompasses all pathological processes that affect the small vessels of the brain. On brain-MRI cSVD is characterized by structural brain abnormalities such as white matter lesions (WMLs). Clinically, cSVD is related to acute syndromes as lacunar stroke but also to more chronic health problems such as cognitive decline. Recent literature suggests that a disrupted blood brain barrier (BBB), leading to elevated BBB permeability, may play a pivotal role in the aetiology of cSVD and lacunar stroke. The BBB is a complex system of neuronal, glial and vascular cells which main function is to shield the brain from toxic components and regulate the homeostasis. Elucidating the role of the BBB may have far reaching consequences for the treatment of cSVD patients and the reduction of recurrence rate of the disease. This could lead to a better quality of life among cSVD patients and reduce the economic burden on society. Currently the exact contribution and extent of a possibly defective BBB in cSVD remains largely unclear, due to the lack of a reliable method to accurately quantify the BBB permeability in cSVD patients. As a result, the current treatment consists of treating the cardiovascular risk factors, often with poor results.
Quantification of the BBB permeability provides an objective measure of the integrity of the BBB and as such aids the study of the role of the BBB. The aim of this study is to realize a clinically applicable MRI-method to quantify the BBB permeability. Moreover, the method can be used to study the involvement of BBB disruption in other neuropathologies including Alzheimer's disease, vascular dementia, hypertension and diabetes.
Primary Study Objective:
To realize a clinically applicable quantification of BBB permeability using DCE-MRI by determining the reproducibility of the DCE-MRI method
Secondary Study Objective:
To achieve the shortest scan duration without compromising the reliability of the BBB permeability quantification.
Hypotheses:
- Using an optimized DCE-MRI method to quantify the BBB permeability, the BBB permeability can be reliably determined in cSVD patients.
- The scan duration can be shortened without compromising the reliability of the BBB permeability quantification.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cortical stroke or primary intracerebral hemorrhage patients: | – | Procedure: Dynamic contrast enhanced Brain MRIpatients who have a clear clinical presentation of either cortical stroke or primary intracerebral hemorrhage confirmed on brain CT. The patients are eligible when the DCE-MRI scans can be performed within 0-6 weeks of the vascular event and on two subsequent days as the vascular permeability may change significantly on the timescale of weeks. |
| cSVD patients | – | Procedure: Dynamic contrast enhanced Brain MRIpatients who present with a transient ischemic attack (TIA) and cSVD related abnormalities on brain MRI. TIA patients are defined as patients with stroke like symptoms that last no longer than 24 hours. MRI abnormalities include extended white matter lesions, (asymptomatic) lacunar infarcts, microbleeds and enlarged Virchow-Robin spaces. The patients are eligible when the first DCE-MRI scan can be performed 8-12 weeks after the TIA to avoid the acute phase, and the second MRI-scan within four weeks after the first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- General: * Age >18 years old * The condition of the patient must be well enough to allow participation in the study, which is decided in consultation with the treating physician. cSVD patients: - patients who present with a transient ischemic attack (TIA) and cSVD related abnormalities on brain MRI. MRI abnormalities include extended white matter lesions, (asymptomatic) lacunar infarcts, microbleeds and enlarged Virchow-Robin spaces. The patients are eligible when the first DCE-MRI scan can be performed 8-12 weeks after the TIA to avoid the acute phase, and the second MRI-scan within four weeks after the first. Cortical stroke or primary intracerebral hemorrhage patients: - patients who have a clear clinical presentation of either cortical stroke or primary intracerebral hemorrhage confirmed on brain CT. The patients are eligible when the DCE-MRI scans can be performed within 0-6 weeks of the vascular event and on two subsequent days.
Key inclusion criteria (6 listed)
- Age >18 years old
- The condition of the patient must be well enough to allow participation in the study, which is decided in consultation with the treating physician.
- cSVD patients: - patients who present with a transient ischemic attack (TIA) and cSVD related abnormalities on brain MRI. TIA patients are defined as patients with stroke like symptoms that last no longer than 24 hours. MRI abnormalities include extended white matter lesions, (asymptomatic) lacunar infarcts, microbleeds and enlarged Virchow-Robin spaces. The patients are eligible when the first DCE-MRI scan can be performed 8-12 weeks after the TIA to avoid the acute phase, and the second MRI-scan within four weeks after the first.
- patients who have a clear clinical presentation of either cortical stroke or primary intracerebral hemorrhage confirmed on brain CT. The patients are eligible when the DCE-MRI scans can be performed within 0-6 weeks of the vascular event and on two subsequent days as the vascular permeability may change significantly on the timescale of weeks.
Key exclusion criteria (9 listed)
- History of cerebrovascular disease (e.g. ischemic/hemorrhagic stroke)
- History of other diseases of the central nervous system (e.g. epilepsy, brain tumor, multiple sclerosis)
- Contra-indications for MRI examination: e.g. pacemaker; neurostimulator; medication pump; cochlear or hearing implant; tattoos or other items that cannot be removed and include metal parts (for instance from operations in the past); metal splinter in the eye; pregnancy and claustrophobia; brain vessel clamps; denture, which contains magnets.
- Contra-indication for MRI contrast agent: e.g. strong suspicion for impaired kidney function (GFR<30ml/min), previous allergic reaction to contrast agent, dialysis patients
- Psychiatric co-morbidity and inability to perform the (DCE-)MRI scans.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dynamic contrast enhanced Brain MRIDCE-MRI is used to quantify the BBB permeability | Procedure or surgery | Cortical stroke or primary intracerebral hemorrhage patients:, cSVD patients |
Primary outcome
pharmacokinetic parameter values Ki and vb
Time frame: day 1 & day 2. Day 2 is min. 24 hours max. 4 weeks after day 1.
Outcome measures of both days are used to determine the reproducibility of the DCE-MRI method.
1 secondary outcome
pharmacokinetic parameter values: Ki and vb for the retrospectively shortened dynamic scans
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2016.
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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.
Cecile RLPN Jeukens, PhD principal investigator
Maastricht 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 Blood-Brain Barrier Permeability and Cerebral Small Vessel Disease, run by Maastricht University Medical Center at 1 site in Netherlands.
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 6 inclusion and 9 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: finished, as of the sponsor's last update on 24 Oct 2016. 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 Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pharmacokinetic parameter values Ki and vb (time frame: day 1 & day 2. Day 2 is min. 24 hours max. 4 weeks after day 1.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Oct 2016.