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Developing a Novel Imaging Biomarker in the Differential Diagnosis of Parkinson's Disease and Parkinsonism

Primary Purpose

Parkinson's Disease

Status
Completed
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
18F-DTBZ
Sponsored by
Chang Gung Memorial Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Parkinson's Disease focused on measuring 18F-DTBZ

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

    i. Male or female patients, age range 20~80. ii. Patients should be fulfilled "UK Parkinson's Disease Society Brain Bank Criteria for the Diagnosis of 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. Twenty 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 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).

  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 " as possible" or "probable" PSP55 (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 CBS whom must:

    i. Male or female patients, age range 20~80. ii. Patients should be fulfilled the"Mayo Clinic proposed criteria for the diagnosis for corticobasal syndrome"56 (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).

  5. Twenty subjects with a diagnosis of VaP whom must:

    i. Male or female patients, age range 20~80. ii. Patients should be fulfilled the clinical diagnostic criteria of vascular parkinsonism. (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).

  6. Twenty subjects with a diagnosis of ET whom must:

    i. Male or female patients, age range 20~80. ii. Patients should be fulfilled the "The Consensus Criteria of the MDS on Essential Tremor"30. (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).

  7. Ten subjects with a diagnosis of DT whom must:

    i. Male or female patients, age range 20~80. ii. Patients should be fulfilled the "The Consensus Criteria of the MDS on Dystonic Tremor"30. (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).

Exclusion Criteria:

  1. Pregnant or becoming pregnant during the study (as documented by pregnancy testing at screening or at any date during the study according to the PI discretion) 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 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 or other neurodegenerative diseases, such as spinocerellar atrophy (SCA), Wilson's disease, hydrocephalus , serious head injury and definite history of neurotoxin exposure, are excluded.
  8. History of allergy to radioligands that contain 18F isotope.

Sites / Locations

  • Chang Gung Memory Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

18F-DTBZ for Parkinson's Disease and parkinsonism

Arm Description

This study will compare the brain uptake of 18F- DTBZ in 20 patients with PD, 20 patients with MSA, 20 patients with PSP, 20 patients with CBS, and 20 patients with VaP, 20 patients with ET, and 10 patients with DT. 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.

Outcomes

Primary Outcome Measures

Analyzing the differences of monoaminergic degeneration between each group by comparing the SUVR of 18F- DTBZ measured by the VOIs methods in each brain region.
During this study, subjects will receive a single i.v. administration of approximately 10 mCi 18F-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.

Secondary Outcome Measures

Statistical parametrical mapping will be performed to compare the early-phase and delayed-phase imaging of 18F- DTBZ PET in each group.
Statistical parametrical mapping (SPM) will be performed to compare the early-phase (cerebral perfusion) and delayed-phase (monoaminergic system) imaging of 18F- DTBZ PET in each group. The capability of 18F- DTBZ PET imaging as an imaging biomarker in differentiating PD and PM will be also investigated.

Full Information

First Posted
February 7, 2014
Last Updated
October 2, 2018
Sponsor
Chang Gung Memorial Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02059733
Brief Title
Developing a Novel Imaging Biomarker in the Differential Diagnosis of Parkinson's Disease and Parkinsonism
Official Title
Developing a Novel Imaging Biomarker in the Differential Diagnosis of Parkinson's Disease and Parkinsonism by 18F-DTBZ PET
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
July 31, 2018 (Actual)
Study Completion Date
July 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chang Gung Memorial Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will compare the brain uptake of 18F- DTBZ in 20 patients with PD, 20 patients with MSA, 20 patients with PSP, 20 patients with CBS, and 20 patients with VaP, 20 patients with ET, and 10 patients with DT.
Detailed Description
Study duration is expected to be completed in a period of 4 year. This study is a uncontrolled, open-label, non-randomized, parallel, and cross-sectional study. Total 130 subjects, including 20 patients with PD, 20 patients with MSA, 20 patients with PSP, 20 patients with CBS, 20 patients with VaP, 20 patients with ET, and 10 patients with DT, 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, laboratory examinations and collecting of adverse events.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
18F-DTBZ

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
18F-DTBZ for Parkinson's Disease and parkinsonism
Arm Type
Experimental
Arm Description
This study will compare the brain uptake of 18F- DTBZ in 20 patients with PD, 20 patients with MSA, 20 patients with PSP, 20 patients with CBS, and 20 patients with VaP, 20 patients with ET, and 10 patients with DT. 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.
Intervention Type
Drug
Intervention Name(s)
18F-DTBZ
Intervention Description
During this study, subjects will receive a single i.v. administration of approximately 10 mCi 18F-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.
Primary Outcome Measure Information:
Title
Analyzing the differences of monoaminergic degeneration between each group by comparing the SUVR of 18F- DTBZ measured by the VOIs methods in each brain region.
Description
During this study, subjects will receive a single i.v. administration of approximately 10 mCi 18F-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.
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Statistical parametrical mapping will be performed to compare the early-phase and delayed-phase imaging of 18F- DTBZ PET in each group.
Description
Statistical parametrical mapping (SPM) will be performed to compare the early-phase (cerebral perfusion) and delayed-phase (monoaminergic system) imaging of 18F- DTBZ PET in each group. The capability of 18F- DTBZ PET imaging as an imaging biomarker in differentiating PD and PM will be also investigated.
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Twenty subjects with a diagnosis of PD whom must: i. Male or female patients, age range 20~80. ii. Patients should be fulfilled "UK Parkinson's Disease Society Brain Bank Criteria for the Diagnosis of 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). Twenty 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 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). 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 " as possible" or "probable" PSP55 (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). Twenty subjects with a diagnosis of CBS whom must: i. Male or female patients, age range 20~80. ii. Patients should be fulfilled the"Mayo Clinic proposed criteria for the diagnosis for corticobasal syndrome"56 (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). Twenty subjects with a diagnosis of VaP whom must: i. Male or female patients, age range 20~80. ii. Patients should be fulfilled the clinical diagnostic criteria of vascular parkinsonism. (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). Twenty subjects with a diagnosis of ET whom must: i. Male or female patients, age range 20~80. ii. Patients should be fulfilled the "The Consensus Criteria of the MDS on Essential Tremor"30. (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). Ten subjects with a diagnosis of DT whom must: i. Male or female patients, age range 20~80. ii. Patients should be fulfilled the "The Consensus Criteria of the MDS on Dystonic Tremor"30. (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). Exclusion Criteria: Pregnant or becoming pregnant during the study (as documented by pregnancy testing at screening or at any date during the study according to the PI discretion) or current breast feeding.. 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. History of drug or alcohol abuse within the last year, or prior prolonged history of abuse. History or presence of QTc prolongation. History of intracranial operation, including thalamotomy, pallidotomy, and/or deep brain stimulation. Any documented abnormality in the brain by CT or MRI of brain, which might contribute to the motor function, such as hydrocephalus and encephalomalacia, will be excluded. Mild cortical atrophy and non-specific white matter changes will be allowed. Patients who have the evidence of secondary parkinsonism or other neurodegenerative diseases, such as spinocerellar atrophy (SCA), Wilson's disease, hydrocephalus , serious head injury and definite history of neurotoxin exposure, are excluded. History of allergy to radioligands that contain 18F isotope.
Facility Information:
Facility Name
Chang Gung Memory Hospital
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan

12. IPD Sharing Statement

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Developing a Novel Imaging Biomarker in the Differential Diagnosis of Parkinson's Disease and Parkinsonism

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