SV2A-PET/CT and PET/MRI Combined Clinical Criteria Score in the Diagnosis of Early Cognitive Alteration

Alzheimer Disease Clinical Trial

Official title:

Synaptic Vesicle Glycoprotein 2A-PET/CT and PET/MRI Combined Clinical Criteria Score in the Diagnosis of Early Cognitive Alteration

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06445582
• Other study ID #: 2023_ky_390
• Status: Not yet recruiting
• Start date: June 2024
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Anhui Provincial Hospital
• Contact: Zehua Zhu, MD
• Phone: 15243611341
• Email: zhuzehua2023[@]ustc.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Using SV2A-PET to character a cohort of patients with early cognitive impairment using the novel synaptic probe 18F-labeled difluoro-analog of UCB-J（also known as 18F-SDM-8）

Description:

A community-based population (Han Chinese) in Hefei, China, based on the CANDI cohort；Single-center prospective case-control study；The projected enrollment population is 80; 40 patients with Alzheimer's Disease（AD）, 30 patients with Mild Cognitive Impairment（MCI）; 10 healthy controls. Diagnostic experiments and predictive prognostic experiments with new probes.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• AD Group

• All diagnostic criteria for AD patients met the National Institute of Neurological Speech-Language Disorders Stroke Institute and Alzheimer's Disease and Related Disorders Association criteria;

• Comply with the American Psychiatric Association Diagnostic and Statistical Workbook of Mental Disorders, 5th edition (DSMIV);

• All subjects were unconscious and could be accompanied by behavioral and psychiatric abnormalities. Subjects who meet the above criteria are eligible for enrollment.

• Those who understand the process of this clinical trial and sign the informed consent form (in addition, non-AD volunteers will be recruited through verbal dissemination and posting of paper advertisements to serve as the non-AD control group, and the final control group will be screened by the clinician and consist of healthy people of similar age and gender).

• MCI Group

• Concerns about cognitive changes, and concerns about finding changes in comparison with one's prior level may originate from the patient himself or herself, from an informed person, or from an experienced specialist;

• Impairment of one or more cognitive areas, primarily memory, executive function, attention, language, and visuospatial function;

• Maintaining independence in daily living, there can be minor impairment in complex instrumental daily abilities;

• Absence of dementia, mild disease, and no evidence of serious impairment of social or occupational abilities;

• Presence of one of the Aß class biomarkers and/ neuronal damage class markers detected by imaging, cerebrospinal fluid;

• All subjects and their guardians give informed consent to the study and sign the informed consent form;

Exclusion Criteria:

• With confirmed cerebrovascular disease, the presence of multiple or extensive cerebral infarcts;

• Other types of dementia: Parkinson's disease dementia, vascular dementia, frontotemporal lobe dementia, dementia with Lewy bodies;

• Sudden onset or stroke-like episodes;

• Early onset of focal neurological symptoms, such as hemiparesis, computational deficits, ataxia, or sensory loss;

• Seizures or gait abnormalities early in the onset of the disease;

• Evidence of drug applications that cause significant effects on cognitive function;

• Those who are allergic to alcohol;

• Persons with alcohol allergy; (ix) Persons with left-handedness; (x) Persons with left-handedness;

• Those with claustrophobia or other reasons for not being able to cooperate with the examination;

• Those with serious heart, liver, lung, kidney and other organ diseases, meeting the above conditions were excluded from the group.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Diagnostic Test:
• [18F]SDM-8
synaptic vesicle glycoprotein 2 A(SV2A)PET tracer [18F]SDM-8

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Anhui Provincial Hospital

References & Publications (7)

Bajjalieh SM, Frantz GD, Weimann JM, McConnell SK, Scheller RH. Differential expression of synaptic vesicle protein 2 (SV2) isoforms. J Neurosci. 1994 Sep;14(9):5223-35. doi: 10.1523/JNEUROSCI.14-09-05223.1994. — View Citation

Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurol. 2018 Oct 1;75(10):1215-1224. doi: 10.1001/jamaneurol.2018.1836. — View Citation

Li S, Cai Z, Wu X, Holden D, Pracitto R, Kapinos M, Gao H, Labaree D, Nabulsi N, Carson RE, Huang Y. Synthesis and in Vivo Evaluation of a Novel PET Radiotracer for Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) in Nonhuman Primates. ACS Chem Neurosci. 2019 Mar 20;10(3):1544-1554. doi: 10.1021/acschemneuro.8b00526. Epub 2018 Nov 16. — View Citation

Nabulsi NB, Mercier J, Holden D, Carre S, Najafzadeh S, Vandergeten MC, Lin SF, Deo A, Price N, Wood M, Lara-Jaime T, Montel F, Laruelle M, Carson RE, Hannestad J, Huang Y. Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain. J Nucl Med. 2016 May;57(5):777-84. doi: 10.2967/jnumed.115.168179. Epub 2016 Feb 4. — View Citation

Naganawa M, Li S, Nabulsi N, Henry S, Zheng MQ, Pracitto R, Cai Z, Gao H, Kapinos M, Labaree D, Matuskey D, Huang Y, Carson RE. First-in-Human Evaluation of 18F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A. J Nucl Med. 2021 Apr;62(4):561-567. doi: 10.2967/jnumed.120.249144. Epub 2020 Aug 28. — View Citation

Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Perez-Canamas A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Sci Transl Med. 2022 Jun;14(647):eabi8593. doi: 10.1126/scitranslmed.abi8593. Epub 2022 Jun 1. — View Citation

Stockburger C, Miano D, Baeumlisberger M, Pallas T, Arrey TN, Karas M, Friedland K, Muller WE. A Mitochondrial Role of SV2a Protein in Aging and Alzheimer's Disease: Studies with Levetiracetam. J Alzheimers Dis. 2016;50(1):201-15. doi: 10.3233/JAD-150687. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SUVR(Standardized Uptake Value Ratio)	Standardized semi-quantitative values of SUVR for each brain region of the cerebral cortex;Standardized Uptake Value ratio (SUVr) is a metric used to evaluate the results of PET scans of the brain. It is a measure of the extent of abnormal metabolism or abnormal deposits in a brain region by comparing the uptake value of a specific brain region to the uptake values of neighboring regions.; SUVr is calculated as follows: first, a reference region is selected, usually an adjacent region of healthy tissue that is unaffected by disease.; then, the uptake value for the region of interest (e.g., the brain region), denoted as SUV, is calculated.; next, the average uptake value of the reference region, denoted as SUVref, is calculated.; finally, the SUVr is calculated, obtained by dividing the SUV of the region of interest by the SUVref of the reference region.	1year
Secondary	AUC(Area under the curve)of SUVR	AUC is defined as the area under the ROC curve enclosed with the axes. ROC (receiver operating characteristic curve) receiver operating characteristic curve, is invented by electronic engineers and radar engineers in World War II used to detect enemy carriers (aircraft, ships) on the battlefield indicators, belongs to the signal detection theory.; The SV2A SUVR calculation was performed using the reference brain region method described above, and the AUC was used to measure the ability of the SUVR to classify the AD disease spectrum versus healthy controls, and its correlation with clinical scale scores was analyzed.	1year