Molecular Imaging of Norepinephrine Transporter (NET) Using [C-11]Methylreboxetine PET in Multiple Sclerosis
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology, Neurology, Multiple Sclerosis |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 7/5/2018 |
| Start Date: | October 10, 2017 |
| End Date: | December 31, 2018 |
| Contact: | Tarun Singhal, M.D. |
| Email: | tsinghal@partners.org |
| Phone: | 6172643043 |
This study aims to use [C-11]MRB PET (positron emission tomography) imaging to look at brain
injury in patients with Multiple Sclerosis (MS) and healthy individuals. The overarching
hypothesis is that there is decreased radioligand binding to the norepinephrine transporter
in multiple sclerosis, reflecting injury to the noradrenergic system and that it plays a role
in disease pathogenesis, its clinical manifestations and severity. This strategy is targeted
to address an unmet need because currently available MRI techniques lack sensitivity and
specificity for assessing such changes in the brains of people with MS.
The specific aims of the study are:
1. To determine norepinephrine transporter binding in the brains of MS patients using
[C-11]MRB PET and compare it with age, and sex matched healthy controls.
2. To determine correlation of norepinephrine transporter binding with clinical severity
and MRI parameters in MS.
3. To determine correlation of norepinephrine transporter binding with fatigue and
cognitive impairment in MS patients.
injury in patients with Multiple Sclerosis (MS) and healthy individuals. The overarching
hypothesis is that there is decreased radioligand binding to the norepinephrine transporter
in multiple sclerosis, reflecting injury to the noradrenergic system and that it plays a role
in disease pathogenesis, its clinical manifestations and severity. This strategy is targeted
to address an unmet need because currently available MRI techniques lack sensitivity and
specificity for assessing such changes in the brains of people with MS.
The specific aims of the study are:
1. To determine norepinephrine transporter binding in the brains of MS patients using
[C-11]MRB PET and compare it with age, and sex matched healthy controls.
2. To determine correlation of norepinephrine transporter binding with clinical severity
and MRI parameters in MS.
3. To determine correlation of norepinephrine transporter binding with fatigue and
cognitive impairment in MS patients.
Two groups of subjects will be recruited:
1. Individuals meeting the definition for Multiple Sclerosis by the International Panel
Criteria19, with an Expanded Disability Status Scale (EDSS) less than 6.5
2. Age- and sex-matched healthy controls
The goal sample size is 12 subjects including 4 healthy controls and 8 subjects with Multiple
Sclerosis (MS).
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 radiopharmaceutical are expected nor have they been reported with
C-11 MRB. As this study is conducted under MGH (Massachusetts General Hospital) RDRC
oversight, the administered dose of C-11 MRB is well below the known level to cause any
pharmacologic effect. Subjects will also be exposed to a small amount of radiation.
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 arterial line 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 clinic, they will
not be allowed to obtain consent from their own patients. Existing MS Center 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 or MGH.
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.
1. Individuals meeting the definition for Multiple Sclerosis by the International Panel
Criteria19, with an Expanded Disability Status Scale (EDSS) less than 6.5
2. Age- and sex-matched healthy controls
The goal sample size is 12 subjects including 4 healthy controls and 8 subjects with Multiple
Sclerosis (MS).
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 radiopharmaceutical are expected nor have they been reported with
C-11 MRB. As this study is conducted under MGH (Massachusetts General Hospital) RDRC
oversight, the administered dose of C-11 MRB is well below the known level to cause any
pharmacologic effect. Subjects will also be exposed to a small amount of radiation.
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 arterial line 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 clinic, they will
not be allowed to obtain consent from their own patients. Existing MS Center 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 or MGH.
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.
Inclusion Criteria:
1. Male and female subjects age 18 to 60 years
2. Subjects willing to undergo PET and MRI imaging
3. Subjects willing and able to give informed consent
Exclusion Criteria:
1. Individuals with a comorbid severe psychiatric condition such as schizophrenia,
bipolar disorder, or post-traumatic stress disorder.
2. Individuals with a known alternate neurologic disorder, previous head injury, or
substance abuse.
3. Individuals taking tricyclic antidepressants, serotonin-norepinephrine reuptake
inhibitors, or norepinephrine-dopamine reuptake inhibitors.
4. Concurrent medical conditions that contraindicate study procedures.
5. 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.
6. Claustrophobia
7. Non-MRI compatible implanted devices
8. Corticosteroid treatment in the past four weeks
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