Florbetapir F 18 PET Imaging of Beta-amyloid in Parkinson's Disease Patients

A Phase 2 Trial of Florbetapir F18 PET Imaging of β-amyloid in Parkinson's Disease Patients With Cognitive Impairment

The primary aim of this study is to compare regional amyloid burden in Parkinson's disease (PD) to normal control subjects. We hypothesize that there will be significant differences in overall amyloid burden in PD patients compared to age-matched normal controls.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: florbetapir F 18

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects may be enrolled if they (inclusion criteria):

  • Are males or females ≥60 years of age
  • Meet research diagnostic criteria for Parkinson's disease:

  • Diagnosis of a parkinsonian syndrome

    • Bradykinesia (slowness of initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive actions)
    • At least one of the following: muscle rigidity, rest tremor, postural instability not due to visual, vestibular, cerebellar or proprioceptive causes

  • Supportive criteria for diagnosis of PD (two or more required)

    • Unilateral onset of symptoms and persistent asymmetry
    • Rest tremor present
    • Progressive illness
    • Excellent response to levodopa with dyskinesias
    • Levodopa response for 5 years or more
    • Clinical course of 10 years or more
  • Have the ability to lie flat and tolerate a 10 minute PET scan.

Exclusion Criteria:

• Subjects may not be enrolled if any of the following are present (exclusion criteria):

  • History of repeated strokes, repeated head injury, definite encephalitis
  • Use of neuroleptics at onset of symptoms
  • Sustained remission
  • Strictly unilateral feature persisting > three years after onset
  • Significant supranuclear gaze palsy
  • Cerebellar, pyramidal and early severe autonomic findings
  • Early severe dementia suggesting a diagnosis of dementia with Lewy bodies (DLB)
  • Imaging study showing structural abnormality that could explain parkinsonism
  • Negative response to an adequate levodopa trial
  • Current clinically significant psychiatric disease that prohibits providing informed consent or participation in the study
  • Current clinically significant endocrine or metabolic disease, pulmonary,
  • Women of childbearing potential who are not two or more years post menopausal or surgically sterilized
  • Have received any investigational medications, or have participated in a trial with investigational medications within the last 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal cognitive performance; Subjects with age-and education-adjusted standardized Mattis Dementia Rating Scale scores of ≥9, indicating normal cognitive performance.	Drug: florbetapir F 18; 10 millicurie (mCi) (370 MBq) florbetapir F 18 Injection; Other Names: Amyvid; 18F-AV-45; florbetapir
Experimental: Mild cognitive deficits; Subjects with age-and education-adjusted standardized Mattis Dementia Rating Scale scores between 6 and 8, inclusive, indicating mild cognitive deficits.	Drug: florbetapir F 18; 10 millicurie (mCi) (370 MBq) florbetapir F 18 Injection; Other Names: Amyvid; 18F-AV-45; florbetapir
Experimental: Severe cognitive impairment; Subjects with age-and education-adjusted standardized Mattis Dementia Rating Scale scores below 5, indicating moderate to severe cognitive impairment.	Drug: florbetapir F 18; 10 millicurie (mCi) (370 MBq) florbetapir F 18 Injection; Other Names: Amyvid; 18F-AV-45; florbetapir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Cortical Amyloid Burden	Standardized uptake value ratios (SUVR) were calculated and compared between subjects with PD and controls. Subjects with Parkinson's Disease (PD) were stratified into one of three groups based on performance on the age and education adjusted Mattis Dementia Rating Scale (DRS-2). The age and education adjusted DRS-2 ranges from 0 (lowest cognitive function) to 20 (highest cognitive function). SUVR is the ratio of tracer uptake in predefined cortical regions, relative to uptake in the whole cerebellum. SUVR values higher than 1 indicate greater amyloid burden in the predefined cortical regions as compared to cerebellum whereas scores less than 1 indicate the opposite. This outcome measure only reports data from the subjects analyzed in this study, the data from normal controls was obtained from a pre-existing database and is not reported here.	50-60 min after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Global Amyloid Burden and Clinical Measures of Cognitive Decline.	Correlation between amyloid burden (global florbetapir SUVR) and cognitive decline (DRS-2 score) was determined using Spearman's rank order correlation method where SUVR was the dependent variable and the DRS-2 score was the independent variable. This analysis was performed for total DRS-2 score and the five DRS-2 subscale scores. The subscales (score range) are: Attention (0-37), Initiation/Perseveration (0-37), Construction (0-6), Conceptualization (0-39) and Memory (0-25). The total DRS-2 score is the sum of the subscale scores and ranges from 0-144. Higher DRS-2 scores indicate greater cognitive function.	50-60 min after injection
Correlation of Florbetapir SUVR With CSF Biomarker Values	Correlation between amyloid burden (florbetapir SUVR) and cerebrospinal fluid (CSF) biomarker values (amyloid beta, tau and phospho-tau) was determined using Spearman's rank order correlation in a subset of subjects undergoing CSF analysis where SUVR was the dependent variable and CSF biomarker values were the independent variables.	50-60 min after injection

Collaborators and Investigators

• Sponsor: Avid Radiopharmaceuticals
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: March 5, 2009
• First Submitted That Met QC Criteria: March 5, 2009
• First Posted (Estimate): March 6, 2009

Study Record Updates

• Last Update Posted (Estimate): March 11, 2013
• Last Update Submitted That Met QC Criteria: February 1, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Parkinson's disease; amyloid burden; florbetapir PET; amyloid PET imaging
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Parkinson Disease; Amyloidosis
• Other Study ID Numbers: 18F-AV-45-A12; 5R43NS063607-02 (U.S. NIH Grant/Contract)