Stroke, IschemicNCT03662750
TSPO PET as a Measure of Post-stroke Brain Inflammation: a Natural History Cohort
A study testing Brain Imaging in people with Stroke, Ischemic and Inflammatory Response, run by Imperial College London at 1 site in United Kingdom.
Trial summary
DESIGN: exploratory, prospective, natural history, imaging cohort study BACKGROUND: Stroke causes a strong inflammatory response in the brain which is thought to contribute to permanent brain damage in stroke patients. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Stroke, Ischemic, Inflammatory Response, Stroke, Acute
- What is being tested?
- Brain Imaging
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 31 Aug 2017to 31 Dec 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations in accordance with all local and national regulations OR according to the local institutional review board's (IRB's)/ethics committee's (EC's) guidelines OR by another process compliant with applicable national laws and regulations and IRB/EC requirement
- Aged 18-85 years of age at the time of informed consent
- Clinical diagnosis of supratentorial acute ischemic stroke within the previous 10 days. Note: An acute brain CT or MRI scan must be available from the patient's history to assess eligibility for the study and be consistent with the diagnosis of acute ischemic stroke.
- Score of at least 5 points on the NIHSS at Screening.
- Subjects of childbearing potential (male and female) must be willing and able to practice effective contraception during the study and for 4 weeks after their Day 90 appointment.
- Negative serum/ urine pregnancy test on all females of childbearing potential within 2 days before each PET study.
Who cannot join
- Unable or unwilling to provide informed consent.
- Presence of acute intracranial hemorrhage on acute brain CT or MRI
- Inability to comply with study requirements (including implanted pacemaker).
- Subject has contraindications to undergoing MRI examination (including, but not limited to metal foreign bodies incompatible with MRI exposure, cardiac pacemakers, renal impairment that contraindicates gadolinium etc.) or PET scan.
- Subject has participated in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with radiation exposure that, when combined with the radiation exposure from the present study, would exceed 10 mSV in addition to the natural background radiation, in the previous 12 months.
- Other unspecified reasons that, in the opinion of the Investigator make the subject unsuitable for enrollment.
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- Nursing or pregnant females or females planning to become pregnant during study participation.
- Claustrophobic, unable to hold head continuously still for 90 minutes, or unwilling to undergo PET or MRI imaging and related procedures required for this study.
- Genetic polymorphism consistent with low TSPO binding affinity (expected in 10% of the population).
Trial locations and contacts
1 site in 1 country.
About this study
DESIGN: exploratory, prospective, natural history, imaging cohort study
BACKGROUND: Stroke causes a strong inflammatory response in the brain which is thought to contribute to permanent brain damage in stroke patients. To develop new therapies targeting inflammation we need to better understand how inflammation affects the injured brain tissue and how it relates to neurological deficits that directly affect the patients' quality of life.
Read more
AIMS: To track the extent and location of inflammation in the brain after stroke over a period of 90 days. The study will explore whether the most inflamed areas in the brain undergo the most damage after stroke and correspond to the cognitive and neurological deficits experienced by stroke patients.
METHODS: The study involves an initial screening visit and 2 study imaging visits at days 15 and 90 after the stroke episode. Patients will undergo:
- Two 90-minute brain imaging sessions using Positron Emission Tomography (PET) (involves injection of safe radiotracers which attach to brain immune cell markers TSPOs and light up the inflamed areas in the brain),
- Two 45-90 minute Magnetic Resonance Imaging (MRI) scanning sessions (include administration of safe chemical contrast agent Gadolinium),
- Physical and neurological examinations (vital signs, assessments of mobility and cognitive functioning),
- Blood testing (routine measurements, blood inflammation markers, and genetic testing for TSPO marker).
Venous cannula will be inserted into the forearm for the duration of the scans.
POPULATION: 15- 25 patients (recruitment will cease once 15 patients have completed the study)
ELIGIBILITY: Male and female stroke patients, aged 18-85, with a recent (within last 10 days) ischemic stroke of moderate severity, able and willing to provide informed consent
LOCATION: Patients will be recruited at the Charing Cross Hospital, Imperial College Healthcare NHS Trust, and study scans will be performed by Invicro Centre for Imaging Sciences, Hammersmith Hospital
DURATION: 18 months FUNDED BY: Biogen Idec Ltd
Read the detailed description
Stroke is a leading cause of mortality and serious long-term disability. There is a substantial unmet medical need for new therapies that can improve outcomes in acute stroke.
Experimental and pathologic data suggest that peri-infarct inflammation contributes to secondary injury after brain ischemia and that blocking inflammation could reduce the volume of brain infarction and improve clinical outcome.
In a recently completed phase 2 placebo-controlled clinical trial, the administration of natalizumab (a potent inhibitor of leukocyte transmigration through the blood -brain barrier [BBB]) in the hyperacute phase of ischemic stroke was associated with beneficial effects in measures of functional outcome, but did not affect the rate of infarct volume growth during a 90-day assessment period. This apparent discrepancy between the lack of effect of anti-inflammatory therapy on lesion size and a substantial beneficial effect on functional outcome in ischemic stroke patients has raised further questions about the manifestation of neuroinflammation, its pathophysiological role and its relation to patients' functional outcome in stroke patients.
The purpose of this imaging study is to characterize the subacute and longstanding extent of upregulation of the neuroinflammation marker TSPO on glial cells at two time points after stroke. The study will also explore the correlation of TSPO upregulation with measures of stroke severity and post-stroke functional outcomes.
The objectives of this study are:
- To characterize TSPO glial expression in specific regions of interest defined on correlative brain MRI (ROIs; infarct, peri-infarct, thalamus) in the subacute (day 15+7) and chronic (day 90+/-7) phases after an ischemic stroke;
- To determine the magnitude and variability of TSPO uptake at these ROIs during the assessment period;
- To describe changes in TSPO expression between 15 and 90 days
- To explore the relationship between TSPO uptake, blood and infarct volume, and measures of Wallerian degeneration,
- To characterize post-stroke TSPO glial expression in relation to measures of stroke severity (infarct size, volume and location; NIHSS) and functional outcome (mRS,BI, depression scale, MoCA)
- To characterize post-stroke TSPO glial expression in relation to systemic inflammatory markers in blood
The endpoints that relate to these objectives are:
- PET-derived measures of TSPO radiotracer uptake in the infarct and peri-infarct areas at day 15 and day 90 after a stroke
- PET-derived measures of TSPO radiotracer uptake in ROIs distant from the infarct area (e.g. thalamus, hippocampi, amygdalae and midbrain) at day 15 and day 90 after a stroke
- Correlation of PET-derived measures with clinical and imaging measures of stroke severity (stroke volume, size and NIHSS) and functional outcome (mRS Barthel index, MoCA, depression, ) at day 15 and day 90
- Correlation of infarct volume and MRI measures of white matter tract injury determined from DTI MRI with measures of thalamic TSPO uptake (time-activity curve; measures of mean and max TSPO uptake on summed image sets fromTSPO PET
- Correlation of PET derived measures with inflammatory markers in the blood (e.g. cytokines)
This is an exploratory, prospective, natural history, imaging cohort study. The recruiting site will be Imperial College Healthcare NHS Trust. All study scans will be performed by Invicro, Hammersmith Hospital
Between 15 and 25 subjects, with recruitment ending when 15 participants have completed all study procedures.
Subjects aged 18-85 with a supratentorial ischemic stroke of moderate severity as measured by NIHSS >4 and evidence of infarction on clinical brain scan at time of stroke:
Subjects will participate in this study for approximately 90 days. No treatment will be started as part of the trial
- Conditions
- Stroke, Ischemic, Inflammatory Response, Stroke, Acute
- Being tested
- Brain Imaging
- Keywords
- TSPO, MRI, PET, Stroke, Brain inflammation
- Medical subject headings
- Ischemic Stroke, Stroke, Encephalitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brain ImagingDiagnostic test
Also called Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET-CT)
The study involves an initial screening visit and 2 study imaging visits at days 15 and 90 after the stroke episode.Patients will undergo:
- Two 90-minute brain imaging sessions using Positron Emission Tomography (PET) (involves injection of safe radiotracers which attach to brain immune cell markers TSPOs and light up the inflamed areas in the brain),
- Two 45-90 minute Magnetic Resonance Imaging (MRI) scanning sessions (include administration of safe chemical contrast agent Gadolinium),
- Physical and neurological examinations (vital signs, assessments of mobility and cognitive functioning),
- Blood testing (routine measurements, blood inflammation markers, and genetic testing for TSPO marker).
Venous cannula will be inserted into the forearm for the duration of the scans.
| Study group | Role | What they receive |
|---|---|---|
| Acute stroke cohort | Experimental | Acute stroke cohort Receives: Diagnostic Test: Brain Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in TSPO Radiotracer Uptake Infarct Area
PET-derived measures of TSPO radiotracer uptake in the infarct and peri-infarct areas at day 90 after a stroke (compared with Day 15)
Measured: 90 days
Changes in TSPO Radiotracer Uptake Distant Area
PET-derived measures of TSPO radiotracer uptake in ROIs distant from the infarct area (e.g. thalamus, hippocampi, amygdalae and midbrain) at day 90 after a stroke (compared with Day 15)
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2018
- Study start31 Aug 2017
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stroke, IschemicStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Exploratory, prospective, natural history, imaging cohort study
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Biogen, Invicro
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03662750
- Sponsor's protocol ID
- GBR-TYS-16-11060
- Status last verified
- Jun 2021
- First submitted
- 2 Aug 2018
- Last updated
- 30 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TSPO PET as a Measure of Post-stroke Brain Inflammation: a Natural History Cohort
- ClinicalTrials.gov ID
- NCT03662750
- Acronym / sponsor ID
- GBR-TYS-16-11060
- Conditions
- Stroke, Ischemic, Inflammatory Response, Stroke, Acute
- Keywords
- TSPO, MRI, PET, Stroke, Brain inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Biogen, Invicro
- Study start
- 31 Aug 2017 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 7 Sep 2018 (actual)
- Results
- Posted 30 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
DESIGN: exploratory, prospective, natural history, imaging cohort study
BACKGROUND: Stroke causes a strong inflammatory response in the brain which is thought to contribute to permanent brain damage in stroke patients. To develop new therapies targeting inflammation we need to better understand how inflammation affects the injured brain tissue and how it relates to neurological deficits that directly affect the patients' quality of life.
AIMS: To track the extent and location of inflammation in the brain after stroke over a period of 90 days. The study will explore whether the most inflamed areas in the brain undergo the most damage after stroke and correspond to the cognitive and neurological deficits experienced by stroke patients.
METHODS: The study involves an initial screening visit and 2 study imaging visits at days 15 and 90 after the stroke episode. Patients will undergo:
- Two 90-minute brain imaging sessions using Positron Emission Tomography (PET) (involves injection of safe radiotracers which attach to brain immune cell markers TSPOs and light up the inflamed areas in the brain),
- Two 45-90 minute Magnetic Resonance Imaging (MRI) scanning sessions (include administration of safe chemical contrast agent Gadolinium),
- Physical and neurological examinations (vital signs, assessments of mobility and cognitive functioning),
- Blood testing (routine measurements, blood inflammation markers, and genetic testing for TSPO marker).
Venous cannula will be inserted into the forearm for the duration of the scans.
POPULATION: 15- 25 patients (recruitment will cease once 15 patients have completed the study)
ELIGIBILITY: Male and female stroke patients, aged 18-85, with a recent (within last 10 days) ischemic stroke of moderate severity, able and willing to provide informed consent
LOCATION: Patients will be recruited at the Charing Cross Hospital, Imperial College Healthcare NHS Trust, and study scans will be performed by Invicro Centre for Imaging Sciences, Hammersmith Hospital
DURATION: 18 months FUNDED BY: Biogen Idec Ltd
Detailed description
Stroke is a leading cause of mortality and serious long-term disability. There is a substantial unmet medical need for new therapies that can improve outcomes in acute stroke.
Experimental and pathologic data suggest that peri-infarct inflammation contributes to secondary injury after brain ischemia and that blocking inflammation could reduce the volume of brain infarction and improve clinical outcome.
In a recently completed phase 2 placebo-controlled clinical trial, the administration of natalizumab (a potent inhibitor of leukocyte transmigration through the blood -brain barrier [BBB]) in the hyperacute phase of ischemic stroke was associated with beneficial effects in measures of functional outcome, but did not affect the rate of infarct volume growth during a 90-day assessment period. This apparent discrepancy between the lack of effect of anti-inflammatory therapy on lesion size and a substantial beneficial effect on functional outcome in ischemic stroke patients has raised further questions about the manifestation of neuroinflammation, its pathophysiological role and its relation to patients' functional outcome in stroke patients.
The purpose of this imaging study is to characterize the subacute and longstanding extent of upregulation of the neuroinflammation marker TSPO on glial cells at two time points after stroke. The study will also explore the correlation of TSPO upregulation with measures of stroke severity and post-stroke functional outcomes.
The objectives of this study are:
- To characterize TSPO glial expression in specific regions of interest defined on correlative brain MRI (ROIs; infarct, peri-infarct, thalamus) in the subacute (day 15+7) and chronic (day 90+/-7) phases after an ischemic stroke;
- To determine the magnitude and variability of TSPO uptake at these ROIs during the assessment period;
- To describe changes in TSPO expression between 15 and 90 days
- To explore the relationship between TSPO uptake, blood and infarct volume, and measures of Wallerian degeneration,
- To characterize post-stroke TSPO glial expression in relation to measures of stroke severity (infarct size, volume and location; NIHSS) and functional outcome (mRS,BI, depression scale, MoCA)
- To characterize post-stroke TSPO glial expression in relation to systemic inflammatory markers in blood
The endpoints that relate to these objectives are:
- PET-derived measures of TSPO radiotracer uptake in the infarct and peri-infarct areas at day 15 and day 90 after a stroke
- PET-derived measures of TSPO radiotracer uptake in ROIs distant from the infarct area (e.g. thalamus, hippocampi, amygdalae and midbrain) at day 15 and day 90 after a stroke
- Correlation of PET-derived measures with clinical and imaging measures of stroke severity (stroke volume, size and NIHSS) and functional outcome (mRS Barthel index, MoCA, depression, ) at day 15 and day 90
- Correlation of infarct volume and MRI measures of white matter tract injury determined from DTI MRI with measures of thalamic TSPO uptake (time-activity curve; measures of mean and max TSPO uptake on summed image sets fromTSPO PET
- Correlation of PET derived measures with inflammatory markers in the blood (e.g. cytokines)
This is an exploratory, prospective, natural history, imaging cohort study. The recruiting site will be Imperial College Healthcare NHS Trust. All study scans will be performed by Invicro, Hammersmith Hospital
Between 15 and 25 subjects, with recruitment ending when 15 participants have completed all study procedures.
Subjects aged 18-85 with a supratentorial ischemic stroke of moderate severity as measured by NIHSS >4 and evidence of infarction on clinical brain scan at time of stroke:
Subjects will participate in this study for approximately 90 days. No treatment will be started as part of the trial
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Exploratory, prospective, natural history, imaging cohort study
| Arm | Type | Receives |
|---|---|---|
| Acute stroke cohort | Experimental | Diagnostic Test: Brain ImagingAcute stroke cohort |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Able to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations in accordance with all local and national regulations OR according to the local institutional review board's (IRB's)/ethics committee's (EC's) guidelines OR by another process compliant with applicable national laws and regulations and IRB/EC requirement
- Aged 18-85 years of age at the time of informed consent
- Clinical diagnosis of supratentorial acute ischemic stroke within the previous 10 days. Note: An acute brain CT or MRI scan must be available from the patient's history to assess eligibility for the study and be consistent with the diagnosis of acute ischemic stroke.
- Score of at least 5 points on the NIHSS at Screening.
- Subjects of childbearing potential (male and female) must be willing and able to practice effective contraception during the study and for 4 weeks after their Day 90 appointment.
Key exclusion criteria (9 listed)
- Unable or unwilling to provide informed consent.
- Presence of acute intracranial hemorrhage on acute brain CT or MRI
- Inability to comply with study requirements (including implanted pacemaker).
- Subject has contraindications to undergoing MRI examination (including, but not limited to metal foreign bodies incompatible with MRI exposure, cardiac pacemakers, renal impairment that contraindicates gadolinium etc.) or PET scan.
- Subject has participated in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with radiation exposure that, when combined with the radiation exposure from the present study, would exceed 10 mSV in addition to the natural background radiation, in the previous 12 months.
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 |
|---|---|---|
| Brain ImagingAlso: Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET-CT)The study involves an initial screening visit and 2 study imaging visits at days 15 and 90 after the stroke episode.Patients will undergo: 1. Two 90-minute brain imaging sessions using Positron Emission Tomography (PET) (involves injection of safe radiotracers which attach to brain immune cell markers TSPOs and light up the inflamed areas in the brain), 2. Two 45-90 minute Magnetic Resonance Imaging (MRI) scanning sessions (include administration of safe chemical contrast agent Gadolinium), 3. Physical and neurological examinations (vital signs, assessments of mobility and cognitive functioning), 4. Blood testing (routine measurements, blood inflammation markers, and genetic testing for TSPO marker). Venous cannula will be inserted into the forearm for the duration of the scans. | Diagnostic test | Acute stroke cohort |
Primary outcome
Changes in TSPO Radiotracer Uptake Infarct Area
Time frame: 90 days
PET-derived measures of TSPO radiotracer uptake in the infarct and peri-infarct areas at day 90 after a stroke (compared with Day 15)
Changes in TSPO Radiotracer Uptake Distant Area
Time frame: 90 days
PET-derived measures of TSPO radiotracer uptake in ROIs distant from the infarct area (e.g. thalamus, hippocampi, amygdalae and midbrain) at day 90 after a stroke (compared with Day 15)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Brain Imaging in people with Stroke, Ischemic and Inflammatory Response, run by Imperial College London at 1 site in United Kingdom.
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 30 Jun 2021. 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 United Kingdom. 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?
Yes. Results are posted in the registry (first posted 30 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Changes in TSPO Radiotracer Uptake Infarct Area (time frame: 90 days). The study lists 2 primary outcomes in all. 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 30 Jun 2021.