Evaluation of [18F]MPPF as a Brain Tracer of Serotonin Receptor 5HT1a

NCT ID: NCT01461083

Last Updated: 2014-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2014-05-31

Brief Summary

The underlying goal of this study is to assess [18F]MPPF PET imaging as a tool to evaluate the activity of the serotonin 5HT1a receptor in the brain of Parkinson Disease (PD) research participants.

Detailed Description

Approximately 40 subjects with Parkinson disease and 20 healthy control subjects will be recruited to participate in the 2 Projects in this study. All subjects will undergo written informed consent and a screening evaluation including baseline clinical laboratory testing, a baseline physical and neurological evaluation and baseline cognitive evaluations.

Subjects in Project 1 (20 PD and 20 HC subjects) will be asked to undergo a single bolus injection of [18F]MPPF followed by serial Positron Emission Tomography (PET) imaging scans and blood sampling for measurement of [18F]MPPF in plasma (both protein bound and free) over a period of up to 2 hours. The imaging analyses will be performed by an image-processing specialist who will remain masked to the procedures employed with each imaging acquisition. The primary imaging outcome measure will be the brain regional distribution volumes expressed as a brain tissue to plasma ratio of the radioligand, [18F]MPPF. Time to the peak uptake and amplitude of the peak uptake will be evaluated for all brain regions and the results for the PD subjects will be compared with the HC subjects.

Subjects participating in Project 2 (20 PD subjects on dopaminergic replacement therapy) will also undergo a second [18F]MPPF and PET imaging session, identical except that PD medications will be withheld for approximately 8 hours prior to the imaging session. The second session will occur greater than 7 days, but not more than 3 months, from the first imaging session. Initial 'on' medication quantitative outcomes for each brain region will be compared to the outcomes from the second 'off' medication imaging session to determine the influence of dopaminergic treatment on 5HT1A activity.

The primary imaging outcome measure will be the brain regional distribution volumes expressed as a brain tissue to plasma ratio of the radioligand, [18F]MPPF. Time to the peak uptake and amplitude of the peak uptake will be evaluated for all brain regions and the results for the PD subjects will be compared with the HC subjects.

Conditions

Parkinson Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

Assess [18F]MPPF and PET imaging

To assess \[18F\]MPPF and PET imaging

Group Type: EXPERIMENTAL

[18F]MPPF

Intervention Type: DRUG

Subjects will be dosed by intravenous bolus injection of \[18F\]MPPF targeted to be 5.0 mCi, and not to exceed 5.5 mCi (not \>10% of 5.0 mCi limit) and not to exceed 5 µg of MPPF

Interventions

[18F]MPPF

Subjects will be dosed by intravenous bolus injection of \[18F\]MPPF targeted to be 5.0 mCi, and not to exceed 5.5 mCi (not \>10% of 5.0 mCi limit) and not to exceed 5 µg of MPPF

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• The participant is 30 years or older.
• Written informed consent is obtained.
• Participants have a diagnosis of PD (based on UK Brain Bank Criteria).
• Modified Hoehn and Yahr stage of 1 - 4.
• For females, non-child bearing potential or a negative urine or blood pregnancy test on day of [18F] CFPyPB injection.

• The participant is 18 years or older.
• Written informed consent is obtained.
• Negative history of neurological or psychiatric illness based on evaluation by a research physician.
• For females, non-child bearing potential a negative urine or blood pregnancy test on day of [18F]MPPF injection.

Exclusion Criteria

• The subject has a clinically significant laboratory value and/or clinically significant unstable medical or psychiatric illness
• The subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion.
• The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
• Evidence of a stroke or mass lesion in a clinically relevant area that may interfere with the imaging outcome measure
• Subject treated with medication known to interfere with [18F]MPPF binding in vivo (e.g. pindolol)
• Subjects with radiation exposure above acceptable levels, i.e. a history of exposure to any radiation >15 mSv over the past 12 months.

Healthy control subjects

• The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness.
• The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
• The subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion.
• Evidence of a stroke or mass lesion in a clinically relevant area that may interfere with the imaging outcome measure
• Subject treated with medication known to interfere with [18F]MPPF binding in vivo (e.g. pindolol)
• Subjects with radiation exposure above acceptable levels, i.e. a history of exposure to any radiation >15 mSv over the past 12 months.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institute for Neurodegenerative Disorders

OTHER

Sponsor Role: lead

Responsible Party

David Russell, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Russell, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute for Neurodegenerative Disorders

Locations

Molecular NeuroImaging, LLC

New Haven, Connecticut, United States

Countries

United States

Related Links

http://www.indd.org

Institute for Neurodegenerative Disorders

Other Identifiers

MPPF

Identifier Type: -

Identifier Source: org_study_id