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Development of a Novel 18F-DTBZ PET Imaging as a Biomarker to Monitor Neurodegeneration of PARK6 and PARK8 Parkinsonism

Primary Purpose

Parkinson's Disease

Status

Completed

Phase

Phase 2

Locations

Taiwan

Study Type

Interventional

Intervention

18F-DTBZ

About this trial

This is an interventional diagnostic trial for Parkinson's Disease

Eligibility Criteria

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

Inclusion Criteria:

Both genders and 20~80 years old.
Written and dated informed consent by self or by legal representative, to be obtained before any of the study procedures.
Twenty PD patients were proved carrying LRRK2 G2385R mutation by our genetic laboratory. Patients didn't have other mutations that may contribute to the parkinsonism, such as LRRK2 G2019S, LRRK2 R1628P, PARK2, PARK6, and SCA2.
Twenty PARK6 PD patients were proved carrying PINK1 mutation by our genetic laboratory. Patients didn't have other mutations that may contribute to the parkinsonism, such as LRRK2, PARK2, and SCA2.
Twenty idiopathic PD patients were proved that they did not carry any known mutations, which may contribute to the parkinsonism, such as LRRK2, PARK2, PARK6, and SCA2. The age of disease onset should be more than 50 years, and no known familial history of parkinsonism or spinocerebellar atrophy.
All the subjects should be fulfilled the UK Parkinson's Disease Society Brain Bank criteria of "possible" or "probable" PD.

Exclusion Criteria:

Pregnant or becoming pregnant during the study or current breast feeding.
Any subject who has a clinically significant abnormal laboratory values, and/or clinically significant or unstable medical or psychiatric illness.
1. Clinically significant hepatic, renal, pulmonary, metabolic, or endocrine disturbances, especially thyroid disease.
2. 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 hi story 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, multiple infarction and encephalomalacia, will be excluded. Mild cortical atrophy and non-specific white matter changes will be allowed.
Any evidence of secondary parkinsonism (multiple infarcts, intoxication, and hydrocephalus, etc).
General PET exclusion criteria.

Sites / Locations

Chang Gung Memory Hpspital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

18F-DTBZ for Parkinson's Disease

Arm Description

This study will compare the brain uptake of 18F- DTBZ in 60 PD patients, including 20 LRRK2 G2385R, 20 PARK6, and 20 idiopathic PD. Subjects will be evaluated sequentially with 18F-DTBZ during a 36 month period. 18F-DTBZ PET scans will be performed twice, at baseline, and 24 (21~27) months following the start of their participation in the study.

Outcomes

Primary Outcome Measures

To calculate the decline rate of striatal 18F-FP-(+)-DTBZ binding and to evaluate whether the degenerative rate differs between idiopathic PD patients and genetic-proving PARK6/PARK8 patients

The annual decline rate of striatal 18F-DTBZ SUVRs (specific uptake value ratios) in PD patients carrying LRRK2 G2385R mutation, PARK6 patients, and patients with idiopathic PD, respectively.

Secondary Outcome Measures

To analyze the correlation between decline rate of 18F-FP-(+)-DTBZ uptake and clinical severity, and access the feasibility of 18F-DTBZ PET imaging as an in vivo biomarker to monitor neurodegeneration in PD

To analyze the correlation between 18F-FP-(+)-DTBZ annual decline rate and the progression rate of clinical motor scores/non-motor scores/ neuropsychiatric tests in each group. Furthermore, to access the utility of 18F-DTBZ PET imaging as an in vivo biomarker to monitor neurodegeneration in PD patients.

Full Information

NCT ID

NCT01759888

First Posted

January 1, 2013

Last Updated

January 23, 2015

Sponsor

Chang Gung Memorial Hospital

Collaborators

National Science Council, Taiwan

1. Study Identification

Unique Protocol Identification Number

NCT01759888

Brief Title

Development of a Novel 18F-DTBZ PET Imaging as a Biomarker to Monitor Neurodegeneration of PARK6 and PARK8 Parkinsonism

Official Title

From Mouse Models to Patients: Development of a Novel 18F-DTBZ PET Imaging as a Biomarker to Monitor Neurodegeneration of PARK6 and PARK8 Parkinsonism

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Completed

Study Start Date

August 2011 (undefined)

Primary Completion Date

December 2014 (Actual)

Study Completion Date

December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chang Gung Memorial Hospital

Collaborators

National Science Council, Taiwan

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The primary objective of this protocol is to access the utility of 18F-DTBZ PET imaging as an in vivo biomarker to monitor neurodegeneration of both PD mouse models and PD patients. Secondary, the investigators will analyze progression rate of genetic-proving PARK8 and PARK6 patients who have homogeneous phenotype and genotype by 18F-DTBZ PET imaging.

Detailed Description

Total of 60 patients, 20 LRRK2 G2385R, 20 PARK6, and 20 idiopathic PD, will be recruited. Subjects will be evaluated sequentially with 18F-DTBZ during a 36 month period. 18F-DTBZ PET scans will be performed twice, at baseline, and 24 (21~27) months following the start of their participation in the study. Subjects will receive a single i.v. administration of approximately 10 mCi 18F-DTBZ immediately prior to imaging. Whitney test will be used to compare the mean standard uptake value ratio (SUVR) values between groups. The decline rate of VMAT2 density will be calculated by comparing the SUVRs of age-matched healthy subjects from our previous studies. 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 each scan (total 6 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

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

49 (Actual)

8. Arms, Groups, and Interventions

Arm Title

18F-DTBZ for Parkinson's Disease

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

18F-DTBZ

Intervention Description

Subjects will receive a single i.v. administration of approximately 10 mCi 18F-FP-(+)-DTBZ (10 nmole FP-(+)-DTBZ) immediately prior to each scan. 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

To calculate the decline rate of striatal 18F-FP-(+)-DTBZ binding and to evaluate whether the degenerative rate differs between idiopathic PD patients and genetic-proving PARK6/PARK8 patients

Description

The annual decline rate of striatal 18F-DTBZ SUVRs (specific uptake value ratios) in PD patients carrying LRRK2 G2385R mutation, PARK6 patients, and patients with idiopathic PD, respectively.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Description

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Both genders and 20~80 years old. Written and dated informed consent by self or by legal representative, to be obtained before any of the study procedures. Twenty PD patients were proved carrying LRRK2 G2385R mutation by our genetic laboratory. Patients didn't have other mutations that may contribute to the parkinsonism, such as LRRK2 G2019S, LRRK2 R1628P, PARK2, PARK6, and SCA2. Twenty PARK6 PD patients were proved carrying PINK1 mutation by our genetic laboratory. Patients didn't have other mutations that may contribute to the parkinsonism, such as LRRK2, PARK2, and SCA2. Twenty idiopathic PD patients were proved that they did not carry any known mutations, which may contribute to the parkinsonism, such as LRRK2, PARK2, PARK6, and SCA2. The age of disease onset should be more than 50 years, and no known familial history of parkinsonism or spinocerebellar atrophy. All the subjects should be fulfilled the UK Parkinson's Disease Society Brain Bank criteria of "possible" or "probable" PD. Exclusion Criteria: Pregnant or becoming pregnant during the study or current breast feeding. Any subject who has a clinically significant abnormal laboratory values, and/or clinically significant or unstable medical or psychiatric illness. Clinically significant hepatic, renal, pulmonary, metabolic, or endocrine disturbances, especially thyroid disease. 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 hi story 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, multiple infarction and encephalomalacia, will be excluded. Mild cortical atrophy and non-specific white matter changes will be allowed. Any evidence of secondary parkinsonism (multiple infarcts, intoxication, and hydrocephalus, etc). General PET exclusion criteria.

Facility Information:

Facility Name

Chang Gung Memory Hpspital

City

Taoyuan

ZIP/Postal Code

333

Country

Taiwan

12. IPD Sharing Statement

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Development of a Novel 18F-DTBZ PET Imaging as a Biomarker to Monitor Neurodegeneration of PARK6 and PARK8 Parkinsonism

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