Clinical trial NCT01461109: Research Involving Subjects With Parkinson's Disease, Alzheimer Disease and Healthy Controls
Official title: Evaluation of [18F] CFPyPB PET as a Marker of Glycine Transporter-1 (GlyT1) Receptor in Subjects With Parkinson Disease, Alzheimer Disease and Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Alzheimer Disease
Keywords: Parkinson Disease
Alzheimer Disease
[18F] CFPyPB
GlyT1
Lead sponsor: Institute for Neurodegenerative Disorders
Sponsor class: OTHER
First posted: 2011-10-27
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The underlying goal of this study is to assess \[18F\] CFPyPB PET imaging as a tool to evaluate the activity of the GlyT1 receptors in the brain of Parkinson's Disease (PD) and Alzheimer Disease (AD) research participants.

Detailed description: Approximately 6 subjects with Parkinson disease, 6 subjects with Alzheimer disease and 20 healthy control subjects will be recruited to participate 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 will be asked to undergo a bolus injection of \[18F\] CFPyPB followed by serial PET imaging scans and plasma sampling for measurement of \[18F\] CFPyPB in plasma (both protein bound and free) over a period of up to 4 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, \[18F\] CFPyPB. Time to the peak uptake and amplitude of the peak uptake will be evaluated for all brain regions and the results for the PD and AD subjects will be compared with the HC subjects.

At least 2 weeks following the initial imaging visit subjects (up to 2 PD subjects, up to 2 AD subjects and up to 5 HC subjects) may be asked to return for a second injection and scanning procedure to evaluate the reproducibility of the imaging measure using this procedure. Subjects may decline participation in the second scan. Subjects will be requested to return for this second scan until enough second scan data is collected to evaluate the imaging outcome measure for reproducibility.

Eligibility criteria: PD subject 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.

PD subject exclusion criteria:

* The subject has a clinically significant abnormal 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.
* The subject has any contraindication to MRI examination, e.g. metal implants or phobia as determined by the onsite radiologist performing the scan.
* The subject is a pregnant or nursing mother

AD subject inclusion criteria:

* The participant is 50 years or older.
* Written informed consent is obtained.
* Participants have a clinical diagnosis of probable Alzheimer disease in accordance with the DSM-IV-TR and according to (NINCDS/ADRDA) criteria.
* Participants do not fulfill the ICC criteria for probable DLB, the NINDS-AIREN for probable vascular dementia, or the Neary \[Neary, et al. 1998\] criteria for FTD.
* Clinical Dementia Rating Scale score 0.5, 1 or 2.
* Modified Hachinski Ischemia Scale score of ≤ 4.
* Geriatric Depression Scale (GDS) ≤ 10.
* For females, non-child bearing potential or a negative urine or blood pregnancy test on day of \[18F\] CFPyPB injection.

AD subject exclusion criteria:

* The subject has a clinically significant abnormal 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.
* The subject has any contraindication to MRI examination, e.g. metal implants or phobia as determined by the onsite radiologist performing the scan.
* The subject is a pregnant or nursing mother.

Healthy volunteer 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 \[18F\] CFPyPB injection.

Healthy volunteer 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.
* The subject has any contraindication to MRI examination, e.g. metal implants or phobia as determined by the onsite radiologist performing the scan.
* The subject is a pregnant or nursing mother.

Primary outcomes:
measure: To assess the dynamic uptake and washout of [18F] CFPyPB
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Perform blood metabolite characterization of [18F] CFPyPB
timeFrame: Approximately 2 years
measure: To obtain safety data
timeFrame: Approximately 2 years
measure: Obtain test/retest reproductibility
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Institute_Neurodegenerative_Disorders
state: Connecticut
Study officials:
affiliation: Institute for Neurodegenerative Disorders
name: David Russell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: