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Establishing 18F-PBR06 PET Imaging as a Viable Pharmacodynamic Endpoint in MSA

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03033680
Recruitment Status : Completed
First Posted : January 27, 2017
Last Update Posted : April 26, 2021
Sponsor:
Information provided by (Responsible Party):
Vikram Khurana, Brigham and Women's Hospital

Tracking Information
First Submitted Date  ICMJE January 24, 2017
First Posted Date  ICMJE January 27, 2017
Last Update Posted Date April 26, 2021
Actual Study Start Date  ICMJE March 24, 2017
Actual Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2017)
Tissue Volume of Distribution [ Time Frame: 1 month ]
PET imaging measurement
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Establishing 18F-PBR06 PET Imaging as a Viable Pharmacodynamic Endpoint in MSA
Official Title  ICMJE Establishing 18F-PBR06 PET Imaging as a Viable Pharmacodynamic Endpoint in MSA
Brief 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.

Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE MSA
Intervention  ICMJE Drug: [F-18]PBR06
PET radiopharmaceutical
Other Name: [18-F]PBR06
Study Arms  ICMJE Experimental: Multiple System Atrophy (MSA)
Eight subjects with a probable MSA diagnosis will be recruited for this study. Each subject will undergo a [F-18]PBR06 PET scan at baseline, and at 9 months follow-up.
Intervention: Drug: [F-18]PBR06
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 22, 2021)
17
Original Estimated Enrollment  ICMJE
 (submitted: January 24, 2017)
4
Actual Study Completion Date  ICMJE January 15, 2021
Actual Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Probable MSA clinical diagnosis.
  2. Male and female subjects age 18 to 70 years.
  3. Motor symptom onset <2 years prior.
  4. Available brain MRI.

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. Corticosteroid treatment in the past four weeks
  7. Non-MRI compatible implanted devices
  8. Low Affinity binders
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03033680
Other Study ID Numbers  ICMJE 2016P002373
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Vikram Khurana, Brigham and Women's Hospital
Study Sponsor  ICMJE Brigham and Women's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Vikram Khuana, MD, PhD Brigham and Women's Hospital
PRS Account Brigham and Women's Hospital
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP