Back to results[18F]PBR111 and Microglial Activation in Multiple Sclerosis
Primary Purpose
Multiple Sclerosis
Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
[18F]PBR111
Sponsored by
About this trial
This is an interventional basic science trial for Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Male or Female, aged 20-70
- Able to read, comprehend and record information written in English.
- Capable of giving written informed consent
- Provide a venous blood sample that will be used for genetics research and the in vitro ligand binding assay.
- A female subject is eligible to participate if she is willing to follow contraception guidelines or if she is of non-childbearing potential.
- Male subjects must agree to use one of the contraception methods
MS subjects:
- Clinical or clinical and laboratory supported diagnosis of multiple sclerosis
- EDSS score up to and including 7.5 at screening evaluation
Healthy Volunteers:
1. Healthy control subjects defined as free from clinically significant active disease as assessed by the Principal Investigator from their medical and psychiatric past and present history
-
Exclusion Criteria:
- If female, positive urine pregnancy test
- An estimated glomerular filtration rate (eGFR) of less than 60 ml/kg/1.73m2
- History or presence of a neurological diagnosis
- Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with radiation exposure.
- Family history of cancer (one or more first-degree relative diagnosed before the age of 55).
- Subject or caregiver is an immediate family member or employee of the participating Investigator, any of the participating site staff or GSK staff.
- Any subject the investigator deems unsuitable for the study (e.g., due to either medical reasons, laboratory abnormalities or subject's unwillingness to comply with all study-related procedures).
- Contraindications to MRI scanning
- Any physical abnormality or functional disability which prevents the subject from acquiring a suitable position for scanning.
- History of or suffers from claustrophobia or feels that he will be unable to lie still on his back in the PET camera or MRI scanner for a period of at least 90mins.
- Unwillingness or inability to follow the procedures outlined in the protocol. -
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
no treatment
Arm Description
Outcomes
Primary Outcome Measures
VT of [18F]PBR111
Regional VT of [18F]PBR111 at baseline in MS patients and age- , gender-, and TSPO binding profile- matched healthy controls
Secondary Outcome Measures
Test-retest variability of regional [18F]PBR111
Test-retest variability of regional [18F]PBR111 VT in 2 consecutive days in MS patients and age- ,gender-, and TSPO binding profile- matched healthy controls
regional [18F]PBR111 VT
Change in regional [18F]PBR111 VT over ~ 4 months after a baseline assessment in MS patients
White matter lesion load and distribution
White matter lesion load (volume of pathological tissue) and distribution as measured by Gadolinium-enhanced and T2-weighted MRI in MS patients
Cortical grey matter lesion load and distribution
Cortical grey matter lesion load and distribution as estimated by the appropriate MRI technique (including high-field MRI in some cases)
Genetic polymorphisms related to the TSPO gene
Genetic polymorphisms related to the TSPO gene and/or genes encoding other proteins which may modulate the binding of ligands to TSPO or TSPO function
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01428505
Brief Title
[18F]PBR111 and Microglial Activation in Multiple Sclerosis
Official Title
A Study to Characterize the Novel TSPO PET Radioligand [18F]PBR111 as an in Vivo Marker of Microglial Activation in Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Terminated
Why Stopped
The Study was terminated because there was insufficient data to complete the study objectives
Study Start Date
July 2011 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a study aimed to characterize [18F]PBR111 as an in vivo marker of microglial activation in Multiple Sclerosis. Regional binding of [18F]PBR111 will be quantified with PET in the brain of up to 24 patients with multiple sclerosis and up to 24 age- and gender- matched healthy volunteers.
Detailed Description
Multiple Sclerosis is characterized by brain areas of focal neuroinflammation. Imaging of microglia activation in multiple sclerosis could represent a useful marker of neuroinflammation. A novel PET tracer with high affinity to TSPO, [18F]PBR111, is a promising tool for PET imaging of activated microglia.
This is a study aimed to characterize [18F]PBR111 as an in vivo marker of microglial activation in Multiple Sclerosis. Regional binding of [18F]PBR111 will be quantified with PET in the brain of up to 24 patients with multiple sclerosis and up to 24 age- and gender- matched healthy volunteers. A subgroup of patients and healthy volunteers will be scanned twice in consecutive days, to test the reproducibility of the measure. Another subgroup of patients will be re-scanned with [18F]PBR111 after 4-6 months. MRI-based measures will be acquired at baseline and, in those patients with later repeat PET scans, also after 4-6 months.
Data from this study will inform about the possible implementation of the [18F]PBR111 ligand to monitor the neuroinflammatory process, disease progression, and response to treatment in MS patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
no treatment
Arm Type
Other
Intervention Type
Radiation
Intervention Name(s)
[18F]PBR111
Intervention Description
radioligand to assess binding to TSPO
Primary Outcome Measure Information:
Title
VT of [18F]PBR111
Description
Regional VT of [18F]PBR111 at baseline in MS patients and age- , gender-, and TSPO binding profile- matched healthy controls
Time Frame
day 30
Secondary Outcome Measure Information:
Title
Test-retest variability of regional [18F]PBR111
Description
Test-retest variability of regional [18F]PBR111 VT in 2 consecutive days in MS patients and age- ,gender-, and TSPO binding profile- matched healthy controls
Time Frame
8 months
Title
regional [18F]PBR111 VT
Description
Change in regional [18F]PBR111 VT over ~ 4 months after a baseline assessment in MS patients
Time Frame
1.5 years
Title
White matter lesion load and distribution
Description
White matter lesion load (volume of pathological tissue) and distribution as measured by Gadolinium-enhanced and T2-weighted MRI in MS patients
Time Frame
1.5 years
Title
Cortical grey matter lesion load and distribution
Description
Cortical grey matter lesion load and distribution as estimated by the appropriate MRI technique (including high-field MRI in some cases)
Time Frame
1.5 years
Title
Genetic polymorphisms related to the TSPO gene
Description
Genetic polymorphisms related to the TSPO gene and/or genes encoding other proteins which may modulate the binding of ligands to TSPO or TSPO function
Time Frame
1.5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male or Female, aged 20-70
Able to read, comprehend and record information written in English.
Capable of giving written informed consent
Provide a venous blood sample that will be used for genetics research and the in vitro ligand binding assay.
A female subject is eligible to participate if she is willing to follow contraception guidelines or if she is of non-childbearing potential.
Male subjects must agree to use one of the contraception methods
MS subjects:
Clinical or clinical and laboratory supported diagnosis of multiple sclerosis
EDSS score up to and including 7.5 at screening evaluation
Healthy Volunteers:
1. Healthy control subjects defined as free from clinically significant active disease as assessed by the Principal Investigator from their medical and psychiatric past and present history
-
Exclusion Criteria:
If female, positive urine pregnancy test
An estimated glomerular filtration rate (eGFR) of less than 60 ml/kg/1.73m2
History or presence of a neurological diagnosis
Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with radiation exposure.
Family history of cancer (one or more first-degree relative diagnosed before the age of 55).
Subject or caregiver is an immediate family member or employee of the participating Investigator, any of the participating site staff or GSK staff.
Any subject the investigator deems unsuitable for the study (e.g., due to either medical reasons, laboratory abnormalities or subject's unwillingness to comply with all study-related procedures).
Contraindications to MRI scanning
Any physical abnormality or functional disability which prevents the subject from acquiring a suitable position for scanning.
History of or suffers from claustrophobia or feels that he will be unable to lie still on his back in the PET camera or MRI scanner for a period of at least 90mins.
Unwillingness or inability to follow the procedures outlined in the protocol. -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
[18F]PBR111 and Microglial Activation in Multiple Sclerosis
We'll reach out to this number within 24 hrs