Clinical trial NCT06445582: SV2A-PET/CT and PET/MRI Combined Clinical Criteria Score in the Diagnosis of Early Cognitive Alteration
Official title: Synaptic Vesicle Glycoprotein 2A-PET/CT and PET/MRI Combined Clinical Criteria Score in the Diagnosis of Early Cognitive Alteration
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Alzheimer Disease
Keywords: Molecular Imaging；
Positron Emission Tomography Computed Tomography；
SV2A protein, human
Lead sponsor: Anhui Provincial Hospital
Sponsor class: OTHER_GOV
First posted: 2024-06-06
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study is a single-center prospective exploratory clinical trial, and given this, it is proposed to initially enroll only 80 evaluable subjects (including 40 patients with ALZHEIMER'S DISEASE, 30 patients with MILD COGNITIVE DISABILITY, and 10 age-sex matched non-ALZHEIMER 'S DISEASE controls), each subject underwent 18F-SDM-8 PET/CT imaging, the ability of the tracer to bind to SV2A in the brain as well as non-specific binding, and correlation analysis with changes in relevant clinical indicators to assess the safety and diagnostic efficacy of the tracer.

Brief 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）

Detailed 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.

Eligibility criteria: 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 Aβ 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.

Primary outcomes:
measure: SUVR（Standardized Uptake Value Ratio）
timeFrame: 1year
Secondary outcomes:
measure: AUC（Area under the curve）of SUVR
timeFrame: 1year
Other outcomes:
Locations:
Study officials:
affiliation: University of Sience and Technology of China
name: Qiang Xie, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.
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.
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.
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.