Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03033680 |
| Other study ID # |
2016P002373 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 24, 2017 |
| Est. completion date |
January 15, 2021 |
Study information
| Verified date |
April 2021 |
| Source |
Brigham and Women's Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The specific aims of the study are:
Primary: To determine the presence and regional distribution of microglial activation, as
assessed by [F-18]PBR06 PET, in subjects with MSA as compared to healthy controls, at
baseline and at 9 months follow-up.
Secondary:
To assess the relationship between microglial activation and clinical progression at baseline
and follow-up.
Hypothesis: The working hypothesis is that there is microglial activation in Multiple System
Atrophy and that the presence and regional distribution of microglial activation is different
in MSA versus healthy controls and correlates with disease severity and comorbidities.
Description:
Sixteen subjects with a probable MSA diagnosis will be recruited for this study. A probable
MSA diagnosis will be based on the following criteria:
- Autonomic failure involving urinary incontinence (inability to control the release of
urine form the bladder, with erectile dysfunction in males) or an orthostatic decrease
of blood pressure within 3 min of standing by at least 30 mmHg systolic or 15 mm Hg
diastolic and
- Poorly levodopa-responsive Parkinsonism (bradykinesia with rigidity, tremor, or postural
instability) or
- A cerebellar syndrome (gait ataxia with cerebellar dysarthria, limb ataxia, or
cerebellar oculomotor dysfunction)
Summary:
Subjects will be recruited during routine clinical appointments by their physician or one of
the other co-investigators listed on the protocol at the Movement Disorders Clinic, 60
Fenwood Road, Boston, MA. Once the subject gives the informed consent, investigators will be
administering standardized questionnaires for assessment of disease severity, comorbidities
and/or presence of symptoms, as applicable to a given cohort. In addition, a blood sample
will be drawn for genotype testing to identify high affinity, medium affinity, and low
affinity binders. Any subjects identified as low affinity binders will be excluded from the
study.
Subjects will undergo two PET scans with [F-18]PBR06 at BWH PET scanning facility at 75
Francis Street, Boston, MA. For PET scanning, an intravenous (IV) catheter will be inserted
for injection of tracer. In addition, prior to the tracer injection, a second IV catheter may
be inserted into the other arm or hand vein on the contralateral side for blood sampling. To
increase the usefulness of blood sampling for radiotracer analysis, the hand or arm used for
blood sampling may be wrapped in an electrical warmer with the thermostat set at 44°C for
approximately 5-10 minutes.The whole PET session will last approximately 120 min. At the time
of imaging, the subjects will be positioned in the gantry of a PET camera. A head support
will be used to minimize head motion.
Side Effects Monitoring:
No side effects from the radiopharmaceutical are expected. The dose of radiopharmaceutical
being administered in this study is below that at which investigators would expect any
effect, including physical dependence and addiction. There will be a follow up phone call
within 24-72 hours after the PET scans, and again 2 weeks after the PET scans to ensure the
subject has not suffered from any side effects. 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 [F-18]PBR06 is a non-FDA approved radioligand, it's use for this study will be
reviewed by Radioactive Drugs Research Committee.
Subject Safety:
Subject monitoring during 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 15 minutes after 45 minutes of PET
scanning, following which the last 60 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.
Recruitment Procedures:
Physicians at Movement Disorders 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. Established Movement Disorders clinic patients may be sent a recruitment
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 for
participation in the study. 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 Procedures:
Informed consent will be obtained from the subjects by a licensed physician investigator on
the study protocol. Existing Movement Disorders clinic subjects may be sent a letter
describing the study and a copy of the consent document. Patients of the clinic may be
introduced to the study through fliers posted throughout the clinic. For the PI's own
patients, the recruitment letter will be sent several weeks before inquiring about their
interest in the study and/or a clinic nurse or a colleague listed on the IRB will introduce
the study using the IRB-approved flier in order to avoid the potential for coercion.
Interested subjects are directed to contact research staff via a telephone number provided in
the letter and on the fliers 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 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 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.
