TSPO PET as a Measure of Post-stroke Brain Inflammation: a Natural History Cohort

NCT03662750 | Completed Results

• 1 other identifier: GBR-TYS-16-11060
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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. 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:

1. 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. 2.Two 45-90 minute Magnetic Resonance Imaging (MRI) scanning sessions (include administration of safe chemical contrast agent Gadolinium),
3. 3.Physical and neurological examinations (vital signs, assessments of mobility and cognitive functioning),
4. 4.Blood testing (routine measurements, blood inflammation markers, and genetic testing for TSPO marker).

Conditions

Stroke, Ischemic; Inflammatory Response; Stroke, Acute

Keywords

TSPO; MRI; PET; Stroke; Brain inflammation

Outcome Measures

Primary Outcomes (2)

• 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)

  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)

  90 days

Study Arms (1)

Acute stroke cohort

EXPERIMENTAL

Acute stroke cohort

Diagnostic Test: Brain Imaging

Interventions

Brain Imaging DIAGNOSTIC_TEST

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.

Also known as: Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET-CT)

Acute stroke cohort

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Imperial College London: lead
• Biogen: collaborator
• Invicro: collaborator

Study Sites (1)

Imperial College London

London, W6 8RF, United Kingdom

Location

MeSH Terms

Conditions

Ischemic Stroke; Stroke; Encephalitis

Interventions

Neuroimaging; Magnetic Resonance Imaging; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Investigative Techniques; Tomography; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Image Enhancement; Photography; Radionuclide Imaging; Diagnostic Techniques, Radioisotope; Tomography, X-Ray Computed; Multimodal Imaging; Radiographic Image Enhancement; Radiography; Tomography, X-Ray

Results Point of Contact

• Title: Prof Roland Veltkamp
• Organization: Imperial College London

r.veltkamp@imperial.ac.uk

020 3311 7296

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Exploratory, prospective, natural history, imaging cohort study

Study Record Dates

• First Submitted: August 2, 2018
• First Posted: September 7, 2018
• Study Start: August 31, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: June 30, 2021
• Results First Posted: June 30, 2021

Record last verified: 2021-06

Locations

GB (1)