Four groups of subjects will be recruited:
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, or at least
one gadolinium enhancing lesion on Magnetic Resonance Imaging (MRI) within 3 months
of enrollment.
Subjects meeting the definition for SPMS by International Panel Criteria and who
have demonstrated deterioration in Expanded Disability Status Scale (EDSS) score in
last 1 year
Subjects meeting the definition for probable AD based on National Institute of
Neurological and Communicable Diseases-Alzheimer's Disease and Related Disorders
Association (NINCDS-ADRDA) criteria. In terms of severity of disease, we will select
subjects with mild AD, as defined by Mini-Mental Status Examination (MMSE) score of
20-26.
Healthy Controls
The study will be performed in two phases. In the early pilot phase, 8 subjects with RRMS
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, rest of the study will
be completed using [F-18]PBR06. All subjects will also undergo 3-Tesla (3T) MRI of the
brain.
The goal sample size is 30 subjects including 6 healthy controls, 8 subjects with
relapsing remitting MS, 8 subjects with secondary progressive MS (SPMS), and 8 subjects
with AD.
Subjects will be recruited by the PI, one of the other co-investigators, or a staff
member listed on the protocol at the Partners MS Center and the Behavioral Neurology
Clinic of Brigham and Women's Hospital.
Side Effects Monitoring:
No side effects from the radiopharmaceuticals are expected. The dose of
radiopharmaceutical being administered in this study is below that at which we would
expect any effect, including physical dependence and addiction. Subjects will be exposed
to a small amount of radiation. The radiotracer will be prepared in such a way as to
ensure that it is sterile and pyrogen free, and its radiochemical purity (RCP) will be
determined using Silica Gel-Instant Thin Layer Chromatography and/or high pressure liquid
chromatography (HPLC). In addition, because both [F-18]PBR06 and [C-11]PBR28 are non-FDA
approved radioligands, their use for this study will be reviewed by Radioactive Drugs
Research Committee.
Subject Safety:
Subject monitoring during MRI and PET scans will be performed using a 2-way intercom
system between the scanner operator and subject and by visual monitoring of the subject
through the window into the scan room (the subject is visible to the operator at all
times).
Subjects will need to lie still in the PET camera for period of 120 min, and subjects may
find it uncomfortable to remain still over this time. Therefore, as mentioned above,
subjects will be given the opportunity to take a break for up to 20 minutes after 70
minutes of PET scanning, following which the last 30 minutes of scanning will be
completed. A standard head-support device will be used to make the subjects comfortable
during the scanning.
If subjects find an intravenous catheter or duration of scanning too uncomfortable, they
are free to withdraw from the study at any time.
The MRI scans take place in a confined space that makes some people claustrophobic.
Claustrophobic individuals will be excluded from the study. Also during the scan the
subject will hear loud banging noises and will therefore wear ear plugs to reduce this
noise.
Recruitment Process:
Physicians at the Partners MS Center and the Brigham and Women's Hospital (BWH)
Behavioral Neurology clinic may present the study to a subject during a regular scheduled
clinic visit. If the subject is interested in the study, a copy of the consent form will
be given. At the time of the subject's initial screening visit, a licensed physician
investigator will answer any questions the subject may have regarding the study and
subsequently obtain informed consent. In accordance with NIH guidelines, efforts will be
made to attain a mix of study participants, in terms of gender and racial/ethnic
representation.
Consent Process:
Informed consent will be obtained from the subjects by a licensed physician investigator
on the study protocol. If the investigator is a clinician from the MS Center or
Behavioral Neurology clinic, they will not be allowed to obtain consent from their own
patients. Existing MS Center or Behavioral Neurology clinic subjects may be sent a letter
describing the study and a copy of the consent document. Interested subjects are directed
to contact research staff via a telephone number provided in the letter inviting
participation in the study to set up a screening visit. They will have the opportunity to
discuss the study with research study staff prior to giving consent as outlined above.
Subjects approached for participation in the study during a routine clinical visit will
have the opportunity to participate in the study at that time or they may choose to
return for participation at another time in the future. All subjects will be informed
that they are free to withdraw consent from the study at any time without affecting the
quality or type of care that they receive at BWH. Subjects will be informed that they may
not qualify for the study if their genetic analysis reveals that they are low affinity
binders for translocator protein (TSPO).
Monitoring and Quality Assurance:
During the study period, subjects will be followed by their clinical neurologists for
adverse events and disease progression. If problems are reported to their physicians,
they will receive care as is normally performed. In addition, the Principal Investigator
(PI) will review all laboratory results of tests undergone by the subjects during the
study period and help co-ordinate any necessary care with patient's primary providers.
