Tau Protein and SV2a Imaging in Patients With Tau Protein-related Diseases

NCT05260151 | Unknown DMC

• 1 other identifier: 2019SQGH5295
• Study Type: observational
• Target: 155
• Locations: 1 country
• Sites: 1

Brief Summary

Tau protein has been identified as one of the key pathological features of Tau proteinopathies, such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD). Tau protein-targeted PET imaging can detect the amount and distribution of Tau protein deposition in human body, and has great research and application value in the diagnosis and evaluation of Tau protein disease. This study will be the first to introduce a complete quantitative, repeatable detection and analysis method in China. For the SV2a tracer \[18F\]MNI-1126, cross-sectional evaluation of its imaging in patients with Tau protein-related diseases and normal controls will be carried out. Later, longitudinal clinical symptoms and two tracers will be evaluated in patients with Tau protein-related diseases and normal controls.(\[18F\]APN1607 and \[18F\]MNI1126) Imaging follow-up to explore longitudinal changes in brain Tau protein deposition and synaptic density in Tau protein-related diseases, thus providing support for future clinical drug trials using imaging biomarkers.

Conditions

Alzheimer Disease; Progressive Supranuclear Palsy; Frontotemporal Dementia

Keywords

Tau; SV2A; PET imaging

Outcome Measures

Primary Outcomes (4)

• The difference of Tau protein deposition and SV2a protein between patients with Tau protein-related diseases and healthy controls

  through the distribution characteristics, time activity curves and kinetic parameters of the tracers in different populations, and to find out the key imaging parameters related to clinical symptoms.

  March 2020 to December 2022.

• To evaluate the longitudinal changes of Tau deposition and SV2a in patients with Tau-related diseases and healthy volunteers

  Changes in each SUVR value or Tau and SV2a distribution were observed in subjects and healthy controls with different diseases

  March 2020 to December 2022.

• To evaluate the correlation between the longitudinal changes of the deposition of Tau and SV2a

  clinical symptoms, MRI and serum biomarkers in patients with Tau-related diseases and healthy volunteers.

  March 2020 to December 2022.

• AE events

  AE events after the subject scan were determined to evaluate the safety of \[18F\]APN-1607 and \[18F\]MNI-1126.

  March 2020 to December 2022.

Study Arms (2)

Cross-sectional validation study

Each tracer's study will enroll 5 normal controls and 5 cases for each relevant disease, which means \[18F\]APN-1607 imaging with arterial line will be performed in 5 normal controls, 15 patients with Alzheimer's disease patients, progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD), and \[18F\] MNI-1126 imaging with Aline test will be performed in 5 normal controls, 15 patients with Alzheimer's disease, progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD); a total of 40 patients will be enrolled in this study group. Patients may choose to participate in the cross-sectional validation study for both tracers, or only for one of them.

Longitudinal study

A total of 115 patients are planned to be enrolled in the study. Among them, AD group will enroll 10 cognitive normal controls, 15 prodromal Alzheimer's disease patients and 15 mild Alzheimer's disease patients. Non-AD group will enroll 15 patients with progressive supranuclear palsy (PSP) , 15 patients with frontotemporal dementia (FTD) carrying MAPT gene, 15 patients with FTD without MAPT gene (carrying other FTD related genes such as C9Orf, Progranulin, CHCHD10 or svPPA with TDP43 gene), 15 non-symptomatic carriers with MAPT mutation and 15 normal controls. Subjects who participated in cross-sectional validation study could also participate in this longitudinal study. Patients may also choose to participate only in the longitudinal study.

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects will be separated into two groups: AD group and Non-AD group. Among them, AD group will include cognitive normal controls, prodromal Alzheimer's disease patients and mild Alzheimer's disease patients. Non-AD group will include patients with progressive supranuclear palsy (PSP) , patients with frontotemporal dementia (FTD) carrying MAPT gene, patients with FTD without MAPT gene (carrying other FTD related genes such as C9Orf, Progranulin, CHCHD10 or svPPA with TDP43 gene), non-symptomatic carriers with MAPT mutation and normal controls.

You may qualify if:

• Males and females aged 40 to 80 years.
• Females have no fertility due to surgery or at least one year after menopause. Otherwise, pregnancy tests should be conducted during screening and every scan visit and should be negative. Males with fertility must use two methods of contraception during the study period and one of them should be barrier contraception. No sperm donation is allowed during the study period and within 90 days after the completion of this study.
• The subject and the subject's legally authorized representative or caregiver should be willing and able to cooperate during the whole research process. According to the judgement of the researcher, there can be a research companion who has regular and sufficient contact with the subjects (spend more than 10 hours a week together). The companion can provide accurate information about the cognitive and functional aspects of the subject, and agrees to accompany the subjects and provide relevant information during the visits. Research companions must be confirmed by researchers that they have sufficient cognitive ability to accurately report subjects' behavior, cognition and function, and can accompany throughout the whole research process with subjects.
• Researchers believe that the subject can complete all the relevant contents of this study.

You may not qualify if:

• Current or prior history of any alcohol or drug abuse within the past 3 years (self report).
• Laboratory tests or ECG with clinically significant abnormalities and/or clinically significant unstable medical illness.
• Radiation exposure received from clinical care prior participation in the last year, combined with that from the present study, exceeds an effective dose of 50 mSV.
• Pregnant, lactating or breastfeeding or intention to become pregnant.
• Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency (including a positive HIV result), pulmonary, or other disorder or disease. Stable, treated chronic medical conditions like hypertension, hypercholesterolemia, diabetes mellitus, non-metastatic dermatologic or prostatic cancer, etc. are acceptable as long as they do not, in the investigator's opinion, contribute to cognitive dysfunction or limit participation in study procedures.
• In the opinion of the investigator, unsuitable to complete lumbar puncture. For example: history of vertebral deformities, major lumbar back surgery, clinically significant back pain, clinically significant abnormal x-ray, and/or injury or taking blood thinners or lab results that would preclude the subject/patient participation or CSF collection during study.
• Veins are not suitable for repeated puncture.
• Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI.
• Daily treatment with anticholinergic antidepressants, typical antipsychotics, or barbiturates, daily treatment with benzodiazepines, opiates, or opioids; treatment with soporifics, stimulants, atypical antipsychotics, centrally acting anticholinergic antihistamines, or centrally acting anticholinergic antispasmodics is prohibited, unless administered intermittently and on a short-term basis and not used within 5 half-lives prior to screening or any neurocognitive assessment.
• Treatment with soporifics, stimulants, atypical antipsychotics, centrally acting anticholinergic antihistamines, or centrally acting anticholinergic antispasmodics is prohibited unless (a) administered daily that initiation or discontinuation of therapy or dose change does not occur within 5 half-lives prior to screening or at any point during the study, or (b) administered intermittently and on a short-term basis and not used within 5 half-lives prior to screening or any neurocognitive assessment.
• Treatment with any therapeutic molecule or treatment that targets Aβ or Tau within 12 months prior to screening.
• Have participated in a clinical trial within 30 days prior to screening or within 5 half-lives since last administration of investigational drug (whichever is greater).
• Researchers consider that other diseases or causes might prevent subjects from completing the entire study.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead
• XINGIMAGING LLC: collaborator
• H. Lundbeck A/S: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator
• Hoffmann-La Roche: collaborator
• Biogen: collaborator
• Hangzhou G-Bio Biotechnology Co., Ltd: collaborator

Study Sites (1)

Xuanwu Hospital

Beijing, Beijing Municipality, 100053, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

venous blood collected with EDTA anticoagulant CSF

MeSH Terms

Conditions

Alzheimer Disease; Supranuclear Palsy, Progressive; Frontotemporal Dementia; Pick Disease of the Brain

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Basal Ganglia Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Biao Chen, M.D., Ph.D

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaohui Sun, Nurse

CONTACT

13466660933; xsun@xingimaging.com

Biao Chen, M.D., Ph.D

CONTACT

135010186287; pbchan@hotmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: March 2, 2022
• Study Start: November 18, 2020
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: March 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)