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

Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01759888
• Other study ID #: 100-1926A
• Status: Completed
• Phase: Phase 2
• First received: January 1, 2013
• Last updated: January 23, 2015
• Start date: August 2011
• Est. completion date: December 2014

Study information

• Verified date: January 2015
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Both genders and 20~80 years old.

2. Written and dated informed consent by self or by legal representative, to be obtained before any of the study procedures.

3. 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.

4. 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.

5. 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.

6. All the subjects should be fulfilled the UK Parkinson's Disease Society Brain Bank criteria of "possible" or "probable" PD.

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.

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.

3. History of drug or alcohol abuse within the last year, or prior prolonged hi story 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. Any evidence of secondary parkinsonism (multiple infarcts, intoxication, and hydrocephalus, etc).

8. General PET exclusion criteria.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Nerve Degeneration
• Parkinson Disease
• Parkinson's Disease
• Parkinsonian Disorders

Intervention

Drug:
• 18F-DTBZ
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.

Locations

Country	Name	City	State
Taiwan	Chang Gung Memory Hpspital	Taoyuan

Sponsors (2)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital	National Science Council, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 years	Yes
Secondary	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.	1 year	Yes