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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Chang Gung Memorial Hospital
Sponsor:
Information provided by (Responsible Party):
NJI90OKM, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01759888
First received: January 1, 2013
Last updated: January 2, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease
Drug: 18F-DTBZ
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Chang Gung Memorial Hospital:

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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 60
Study Start Date: August 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 18F-DTBZ for Parkinson's Disease
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.
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.

Other Name: 18F-DTBZ

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.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01759888

Locations
Taiwan
Chang Gung Memory Hpspital Recruiting
Taoyuan, Taiwan, 333
Contact: Chin-Song Lu    +886 975365688    c81214@cgmh.org.tw   
Principal Investigator: Chin-Song Lu, Professor         
Sponsors and Collaborators
Chang Gung Memorial Hospital
  More Information

No publications provided

Responsible Party: NJI90OKM, Professor, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT01759888     History of Changes
Other Study ID Numbers: 100-1926A
Study First Received: January 1, 2013
Last Updated: January 2, 2013
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Nerve Degeneration
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 19, 2014