The Differential Diagnosis of Parkinson's Disease and Parkinsonism by Positron-emission Tomography

The Differential Diagnosis of Parkinson's Disease and Parkinsonism by Positron-emission Tomography With Vesicular Monoamine Transporter Ligand (18F-DTBZ)

The objective of this protocol is to analyze the sensitivity and specificity of 18F-DTBZ PET to the differential diagnosis of Parkinson's disease (PD) and other parkinsonism disorders, including multiple system atrophy (MSA), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP).

Study Overview

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

Detailed Description

40 patients with PD, 40 patients with MSA, 20 patients with CBD, and 20 patients with PSP, will be enrolled. Each evaluable subject involved in this study must fulfill all the inclusion and exclusion criteria according the subject grouping, each subject will have 3 visits in this study, as one screening visit, one imaging visit, and one safety evaluation visit.

Safety measurement will be evaluated by medical history, vital signs, physical examinations,

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 333
    • Chang Gung Memory Hpspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Forty subjects with a diagnosis of PD whom must:

   i.Male or female patients, age range 20~80. ii.Patients should be fulfilled Criteria of diagnosis of Parkinson disease8 of "possible" or "probable" PD (Appendix I).

   iii.Patients who provide a written informed consent prior to study entry. If the patient is incapable of informed consent, the caregiver may consent on behalf of the patient (the patient must still confirm assent).

2. Forty subjects with a diagnosis of MSA whom must:

   i.Male or female patients, age range 20~80. ii.Patients should be fulfilled the Consensus diagnostic criteria of "possible" or "probable" MSA14 (Appendix II).

   iii. Patients who provide a written informed consent prior to study entry. If the patient is incapable of informed consent, the caregiver may consent on behalf of the patient (the patient must still confirm assent).

3. Twenty subjects with a diagnosis of PSP whom must:

   i.Male or female patients, age range 20~80. ii.Patients should be fulfilled the NINDS-SPSP clinical criteria for the diagnosis of PSP of "possible" or "probable" PSP35 (Appendix III).

   iii.Patients who provide a written informed consent prior to study entry. If the patient is incapable of informed consent, the caregiver may consent on behalf of the patient (the patient must still confirm assent).

4. Twenty subjects with a diagnosis of CBD whom must:

   i.Male or female patients, age range 20~80. ii.Patients should be fulfilled the Kumar's criteria of CBD36 (Appendix IV). iii.Patients who provide a written informed consent prior to study entry. If the patient is incapable of informed consent, the caregiver may consent on behalf of the patient (the patient must still confirm assent).

Exclusion Criteria:

1. Pregnant or becoming pregnant during the study or current breast feeding.

2. Any subject who has a clinically significant abnormal laboratory values, and/or clinically significant or unstable medical or psychiatric illness.

   i.Clinically significant hepatic, renal, pulmonary, metabolic, or endocrine disturbances.

   ii.Current clinically significant cardiovascular disease. (cardiac surgery or myocardial infarction within the last 6 months; unstable angina; decompensated congestive heart failure; significant cardiac arrhythmia; congenital heart disease.

3. History of drug or alcohol abuse within the last year, or prior prolonged history of abuse.
4. History or presence of QTc prolongation.
5. History of intracranial operation, including thalamotomy, pallidotomy, and/or deep brain stimulation.
6. Any documented abnormality in the brain by CT or MRI of brain, which might contribute to the motor function, such as hydrocephalus, multiple infarction and encephalomalacia, will be excluded. Mild cortical atrophy and non-specific white matter changes will be allowed.
7. Patients who have the evidence of secondary parkinsonism (multiple infarcts, intoxication, and hydrocephalus, etc) or other neurodegenerative diseases, such as spinocerebellar atrophy (SCA), Wilson's disease, hydrocephalus, multiple infarction, serious head injury and definite history of neurotoxin exposure, are excluded.
8. General PET exclusion criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• 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: 18F-DTBZ for Parkinson's Disease; This study will compare the brain uptake of 18F- DTBZ in 40 patients with PD, 40 patients with MSA, 20 patients with CBD, and 20 patients with PSP . Each evaluable subject involved in this study must fulfill all the inclusion and exclusion criteria according the subject grouping, each subject will have 3 visits in this study. Safety measurement will be evaluated by medical history, vital signs, physical examinations, laboratory examinations and collecting of adverse events.

Drug: 18F-FDG; During this study, subjects will receive a single i.v. administration of approximately 10 mCi 18F-FP-(+)-DTBZ immediately prior to imaging. The proposed dose for this study is based on our phase I study. At the proposed human dose of 10 mCi, the whole body effective dose (ED) will be approximately 680 mrem. The estimated human ED is expected to be comparable to or below the range of other approved brain imaging agents, such as 18F-FDG.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To analyze the sensitivity and specificity of 18F-DTBZ PET to the differential diagnosis of PD ,PSP,MSA,CBD.	All subjects that received 18F-FP-(+)-DTBZ for injection.Sensitivity and specificity analysis of VMAT2 imaging will include all subjects for whom there is sufficient data to evaluate the parameter in question.Descriptive statistics will be presented to help detect changes within groups or differences between groups (PD vs. MSA, CBD, PSP). The descriptive statistics will include mean, standard deviation, median, and ranges for continuous variables, and frequency and percent frequency for categorical variables.Mann Whitney test will be used to compare the mean SUVR values between PD and other groups. ROC curve will be used to determinate the diagnostic threshold of SUVR and the sensitivity and specificity of 18F- DTBZ PET in the differentiating PD, MSA, PSP, and CBD. Statistical analysis was performed using a unpaired t test based on one contrast to test a hypothesis of regional abnormal uptakes of 18F-DTBZ in an individual MSA/PSP/CBD patient compared to a PD group.	3 years

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: National Science Council, Taiwan

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: March 12, 2013
• First Submitted That Met QC Criteria: March 31, 2013
• First Posted (Estimate): April 4, 2013

Study Record Updates

• Last Update Posted (Estimate): November 13, 2013
• Last Update Submitted That Met QC Criteria: November 10, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: 18F-FDG
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: 98-3626A