Topography Staging and Dual Phase Image Quantification of Tau PET in Cognitive Impairment Subjects

A second-generation tau PET image tracer 18F-PM-PBB3 (APN-1607 or MNI-958) has been developed by National Institute of Radiological Sciences. The new tracer solved the off-target binding issue. This study will evaluate new quantitative methods with PMPBB3, by utilized dual phase scanning protocol to extract blood flow and Tau protein binding information, to evaluate appropriate reference brain regions, to improve the normalization efficiency of brain imaging, and to establish a brain template image analysis platform.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: F-18 PMPBB3

Detailed Description

Dementia is the top issue in the aging society. Aging population also has its negative implications for the global economy. Effective diagnosis and treatment of dementia is important. Alzheimer's disease accounts for more than 60% of dementia. The main pathological features are the amyloid deposition and Tau neurofibrillary tangles. Currently, our understanding for these misfolded proteins and dementia is limited. There is a need for development of new imaging biomarkers to help clarify the pathophysiology of dementia. In recent years, molecular imaging technology has developed rapidly. In addition to amyloid imaging tracer have been put into clinical use, Tau protein imaging biomarkers have also entered clinical research. However, the tau protein within the patient's brain is not evenly distributed. And the amount of the Tau protein radioactivity is not simply correlate to dementia disease staging. In addition, the problem of off-target binding of the first generation of tracers has yet to be resolved. Recently a second-generation tau PET image tracer 18F-PM-PBB3 (APN-1607 or MNI-958) has been developed by National Institute of Radiological Sciences. The new tracer solved the off-target binding issue. This study will evaluate new quantitative methods with PMPBB3, by utilized dual phase scanning protocol to extract blood flow and Tau protein binding information, to evaluate appropriate reference brain regions, to improve the normalization efficiency of brain imaging, and to establish a brain template image analysis platform. The investigators will evaluate the relationship between Tau protein uptake pattern and disease classifications, and the correlation between Tau protein neurofibrillary tangles and amyloid deposition, and the correlation between MRI and glucose brain connectivity. Finally, to understand the pathophysiology of Tau protein in dementia disease.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kun-Ju MD Lin; Phone Number: 2632 03-3281200; Email: kunjulin@gmail.com

Study Locations

• Taiwan
  • Guishan Dist
    • Taoyuan City, Guishan Dist, Taiwan, 333
      • Recruiting
      • Chang Gung Memorial Hospital,Linkou
      • Contact: Kun-Ju Lin; Phone Number: 2632 03-3281200; Email: kunjulin@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1.1 All subjects

1. Age between 55-80 years
2. Written informed consent must be obtained before any assessment is performed.
3. Female subjects must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal ligation) or post-menopausal for at least 1 year or, if they are of child-bearing potential, must commit to use a barrier contraception method for the duration of the study.
4. Male subjects and their partners of childbearing potential must commit to the use of two methods of contraception, one of which is a barrier method for male subjects for the study duration.
5. Male subjects must not donate sperm for the study duration.
6. Willing to undergo repeated MRIs and at least two PET scans.

1.2 Patient with Prodromal AD or AD dementia

1. Patients fulfill the criteria of prodromal AD or AD dementia based on IWG-2 criteria
2. Able to provide written informed consent with reliable carer in AD population. The participant should have reading ability OR 6/more years of formal education OR with working experiences.

1.3 Cognitive normal control

1. Cognitive unimpaired individual is defined as normal control in this study. Cognitive un-impaired normal control is defined as cognitive performance in the non-impaired range for that individual, defined as not mild cognitive impairment or demented).
2. The normal control should have their clinical dementia rating score 0
3. Cognitive Ability Screening Instrument (CASI) scores rated >50 percentile.

Exclusion Criteria:

1. Already receive outpatient clinic follow-ups with diseases that may affect the cognitive evaluation or presentation that include but not limited to Parkinsonism, Parkinson's disease dementia, schizophrenia, major depression, epilepsy, alcohol or drug abuse, major head trauma with consciousness loss
2. Severe progressive or unstable systemic disease that may interfere with the follow-up and test results. These included but not limited to cancer in the past 5 years, end stage renal or liver dysfunction, clinical significant myocardial infarction (New York Heart Association Functional Classification III-IV), Active disease that received admission in the past one year and unstable angina. Other diseases that were not listed but may interfere with the follow-up or test will be judged by the principle investigator.
3. Any treatment that suggests any of the aforementioned disease will be excluded.
4. Depression with ongoing diagnosis and treatment, suicide idea or suicide behavior in the past 6 months.
5. Contraindications or previously failure for receiving brain magnetic resonance imaging or PET scan.
6. History of risk factors for torsades de pointes (a cardiac dysrhythmia associated with sudden death) or taking medications known to prolong the QT interval.
7. Have an ECG obtained prior to the 18F-PM-PBB3 PET scan that in the opinion of the investigator is clinically significant regarding the subject's participation in the study.
8. Pregnant, lactating or breastfeeding.
9. Patients with severe liver disease (such as ALT > 3x upper limit of normal).

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: F-18-PMPBB3; F-18-PMPBB3 imaging	Drug: F-18 PMPBB3; The study will enroll 200 patients with prodromal AD and AD dementia and 100 normal controls, men and women aged 55-80 years across core clinical criteria of prodromal AD and mild AD dementia based on IWG-2 criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tau Distribution Among Normal, Prodromal AD and AD Dementia Subjects Measured by Standardized Uptake Value Ratio (SUVR) as Assessed by 18F-PM-PBB3 tau PET Scan.	4 years

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): March 31, 2023
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: November 4, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Dementia; Tau PET scan; Tau neurofibrillary tangles; Amyloid deposition
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: 201801834A0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No