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

Phase I Evaluation of [18F]MPPF as a Brain Tracer of Serotonin Receptor 5HT1a in Subjects With Parkinson Disease and Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: [18F]MPPF

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Molecular NeuroImaging, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

PD Subjects

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.

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

Inclusion criteria:

• 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 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.

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Assess [18F]MPPF and PET imaging; To assess [18F]MPPF and PET imaging	Drug: [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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the dynamic uptake and washout of [18F]MPPF in brain using positron emission tomography(PET) imaging	To assess the dynamic uptake and washout of [18F]MPPF in brain using positron emission tomography (PET) in Parkinson disease and similarly aged healthy control subjects as a potential imaging biomarker of the serotonin (5HT1A) receptor in brain.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the influence of dopaminergic replacement therapy on 5HT1A activity in PD subjects	To assess the influence of dopaminergic replacement therapy on 5HT1A activity in PD subjects	2 years

Collaborators and Investigators

• Sponsor: Institute for Neurodegenerative Disorders

Publications and helpful links

Helpful Links

• Institute for Neurodegenerative Disorders

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: September 27, 2011
• First Submitted That Met QC Criteria: October 25, 2011
• First Posted (Estimate): October 27, 2011

Study Record Updates

• Last Update Posted (Estimate): June 4, 2014
• Last Update Submitted That Met QC Criteria: June 2, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Parkinson Disease; [18F]MPPF
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: MPPF