[18F]PBR111 and Microglial Activation in Multiple Sclerosis

This study has been terminated.
(The study was terminated because there was enough data to complete the study objectives and so the study was terminated slightly earlier than planned)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01428505
First received: September 1, 2011
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Radiation: [18F]PBR111
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Study to Characterize the Novel TSPO PET Radioligand [18F]PBR111 as an in Vivo Marker of Microglial Activation in Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • VT of [18F]PBR111 [ Time Frame: day 30 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
    Change in regional [18F]PBR111 VT over ~ 4 months after a baseline assessment in MS patients

  • White matter lesion load and distribution [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
    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


Enrollment: 50
Study Start Date: July 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
no treatment
none
Radiation: [18F]PBR111
radioligand to assess binding to TSPO

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.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or Female, aged 20-70
  2. Able to read, comprehend and record information written in English.
  3. Capable of giving written informed consent
  4. Provide a venous blood sample that will be used for genetics research and the in vitro ligand binding assay.
  5. A female subject is eligible to participate if she is willing to follow contraception guidelines or if she is of non-childbearing potential.
  6. Male subjects must agree to use one of the contraception methods

MS subjects:

  1. Clinical or clinical and laboratory supported diagnosis of multiple sclerosis
  2. 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:

  1. If female, positive urine pregnancy test
  2. An estimated glomerular filtration rate (eGFR) of less than 60 ml/kg/1.73m2
  3. History or presence of a neurological diagnosis
  4. Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with radiation exposure.
  5. Family history of cancer (one or more first-degree relative diagnosed before the age of 55).
  6. Subject or caregiver is an immediate family member or employee of the participating Investigator, any of the participating site staff or GSK staff.
  7. 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).
  8. Contraindications to MRI scanning
  9. Any physical abnormality or functional disability which prevents the subject from acquiring a suitable position for scanning.
  10. 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.
  11. Unwillingness or inability to follow the procedures outlined in the protocol. -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01428505

Locations
United Kingdom
GSK Investigational Site
London, United Kingdom, W12 0NN
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01428505     History of Changes
Other Study ID Numbers: 115241
Study First Received: September 1, 2011
Last Updated: December 19, 2013
Health Authority: United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 21, 2014