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Microglial Activation Positron Emission Tomography (PET) Brain Imaging in Multiple Sclerosis and Alzheimer's Disease (MAPET)

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ClinicalTrials.gov Identifier: NCT02649985
Recruitment Status : Recruiting
First Posted : January 8, 2016
Last Update Posted : December 11, 2020
Sponsor:
Information provided by (Responsible Party):
TARUN SINGHAL, Brigham and Women's Hospital

Brief Summary:

The specific aims of the study are:

Primary: To determine the presence and regional distribution of microglial activation, as assessed by Fluorine-18 (18F) labeled "Peripheral Benzodiazepine Receptor 06" (PBR06) -PET, in subjects with active Relapsing Remitting Multiple Sclerosis (RRMS), Secondary Progressive Multiple Sclerosis (SPMS), and Alzheimer's Disease (AD) as compared to healthy controls

Secondary:

  1. To assess the relationship between microglial activation and clinical variables including disease severity and comorbidities (such as pain, fatigue and/or depression), as well as clinical MRI findings (such as lesions and atrophy)
  2. A pilot substudy aims to establish the non-inferiority of [F-18]PBR06 as compared with Carbon-11 [C-11] labeled "Peripheral Benzodiazepine Receptor 28" (PBR28) PET in patients with RRMS.

Hypothesis: The working hypothesis is that there is microglial activation in multiple sclerosis and Alzheimer's disease as compared to healthy controls and that the pattern/ regional distribution of microglial activation is different in Multiple Sclerosis (MS) versus AD and correlates with disease severity and comorbidities.

In addition, the investigators hypothesize that [F-18]PBR06-PET scans will be at least as good as [C-11]PBR28-PET scans, the current gold standard.


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Alzheimer's Disease Drug: [F-18]PBR06 Drug: [C-11]PBR28 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Microglial Activation Positron Emission Tomography (PET) Brain Imaging in Multiple Sclerosis and Alzheimer's Disease
Actual Study Start Date : May 2, 2016
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Relapsing-Remitting Multiple Sclerosis

Subjects meeting the definition for RRMS by the International Panel Criteria, who are active, as defined by at least one MS relapse in the past 12 months, at least one gadolinium enhancing lesion on a MRI within 12 months of enrollment, or at least one new FLAIR bright lesion on MRI within 6 months of enrollment.

The study will be performed in two phases. In the early pilot phase, 8 subjects with multiple sclerosis will undergo both [C-11]PBR28 PET scan and [F-18]PBR06 PET scan. At the end of this phase, a formal interim analysis will be performed and if imaging characteristics of [F-18]PBR06 are found non-inferior to or better than [C-11]PBR28, the rest of the study will be completed using [F-18]PBR06. On the other hand, if [F-18]PBR06 is found to be inferior to [C-11]PBR28, the rest of the study will be pursued using [C-11]PBR28.

Drug: [F-18]PBR06
PET radiopharmaceutical
Other Name: [F-18] PBR06

Drug: [C-11]PBR28
PET radiopharmaceutical
Other Name: [C-11] PBR28

Experimental: Progressive Multiple Sclerosis
Subjects meeting the definition for SPMS/PPMS (Primary Progressive Multiple Sclerosis) by International Panel Criteria and who have demonstrated deterioration in EDSS score in last 1 year.
Drug: [F-18]PBR06
PET radiopharmaceutical
Other Name: [F-18] PBR06

Active Comparator: Alzheimer's Disease
Subjects meeting the definition for probable AD based on NINDS-ADRDA criteria. In terms of severity of disease, the investigators will select subjects with mild AD, as defined by Mini-Mental Status Examination (MMSE) score of 20-26.
Drug: [F-18]PBR06
PET radiopharmaceutical
Other Name: [F-18] PBR06

Healthy Control
This group will serve as non disease population.
Drug: [F-18]PBR06
PET radiopharmaceutical
Other Name: [F-18] PBR06

Experimental: Multiple Sclerosis Ocrelizumab

Subjects who have been prescribed Ocrelizumab by their treating MS neurologist but have not yet started the first Ocrelizumab infusion.

Subjects will undergo two separate visits for [F-18]PBR06 PET scans, once before starting Ocrelizumab and the second visit 3 months after completion of the initial Ocrelizumab doses.

Drug: [F-18]PBR06
PET radiopharmaceutical
Other Name: [F-18] PBR06




Primary Outcome Measures :
  1. Tissue Volume of Distribution [ Time Frame: 1 month ]
    PET imaging measurement


Secondary Outcome Measures :
  1. Standardized uptake values (SUV)/Standardized uptake value Ratios (SUVR) [ Time Frame: 1 month ]
    PET imaging measurement



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male and female subjects age 18 to 70 years. For Alzheimer's Disease patients and healthy controls, the age range is going to be 18 to 85 years.
  2. For RRMS, it needs to be active, which is defined as at least one relapse in the past 12 months, at least one gadolinium enhancing lesion on MRI within 12 months of enrollment or at least one new FLAIR bright lesion on MRI within 6 months of enrollment.
  3. For SPMS, deterioration in EDSS score in the last year is required.
  4. For the subjects in the Ocrelizumab arm, only the subjects who have already been prescribed Ocrelizumab by their treating MS neurologist but have not yet started the first infusion, will be included.
  5. AD subjects with MMSE score of 20-26.
  6. Subjects willing to undergo PET and MRI imaging
  7. Subjects willing and able to give informed consent

Exclusion Criteria:

  1. Individuals with a known alternate neurologic disorder, previous head injury, or substance abuse.
  2. Individuals with bipolar disease and schizophrenia
  3. Concurrent medical conditions that contraindicate study procedures.
  4. Women who are pregnant or nursing. Also, any woman who is seeking to become pregnant or suspects she is pregnant will be excluded from enrollment.
  5. Claustrophobia
  6. Non-MRI compatible implanted devices
  7. For the Ocrelizumab arm, subjects already on Ocrelizumab will be excluded. For the Alemtuzumab arm, subjects already on Alemtuzumab will be excluded.
  8. For the Ocrelizumab arm and the Alemtuzumab arm, subjects with abnormal serum creatinine will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02649985


Contacts
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Contact: Tarun Singhal, MD 617-264-3043 tsinghal@bwh.harvard.edu

Locations
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United States, Massachusetts
Partners MS Center, 60 Fenwood Road Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jack Ficke    617-264-3044    jficke@bwh.harvard.edu   
Contact: Steven Cicero       scicero@bwh.harvard.edu   
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
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Principal Investigator: Tarun Singhal, MD Brigham and Women's Hospital
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Responsible Party: TARUN SINGHAL, Assistant Professor of Neurology, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT02649985    
Other Study ID Numbers: 2015P002329
First Posted: January 8, 2016    Key Record Dates
Last Update Posted: December 11, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Alzheimer Disease
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Dementia
Brain Diseases
Central Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders