Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05360082
Other study ID # S66610
Secondary ID
Status Not yet recruiting
Phase
First received
Last updated
Start date September 2024
Est. completion date December 2025

Study information

Verified date May 2024
Source Universitaire Ziekenhuizen KU Leuven
Contact Koen Van Laere, MD PhD DSc
Phone +3216343714
Email koen.vanlaere@uzleuven.be
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Positron Emission Tomography (PET) is a functional imaging technique, which enables in vivo visualization of biological molecules expressed in human tissues. Brain PET is most powerful to study a vast range of neurological and psychiatric disorders in vivo, targeting neuronal and glial activity, metabolism, cerebral blood flow, receptor proteins or misfolded proteins. In vivo imaging of synaptic density in the human brain has become feasible through development of [11C]UCB-J, a PET radioligand for the synaptic vesicle protein SV2A, which is ubiquitously and homogeneously present in presynaptic terminals throughout the brain. A first study in Huntington's disease (HD) mutation carriers showed loss of striatal [11C]UCB-J binding (also when corrected for atrophy), as well as in the neocortex (Delva et al, Neurology 2022). Moreover, regional synaptic loss was highly correlated to motor impairment. In order to be able to use SV2A PET as widespread available biomarker tool to assess synaptic integrity, disease progression and/or response to mHTT lowering drugs, the short half-life of 11C (20 minutes) for [11C]UCB-J remains a hurdle. Recently, [18F]SynVesT-1, an optimized 18F-labeled analogue of [11C]UCB-J with similar kinetics, binding affinity, and test-retest precision properties has been evaluated in humans. However, there is evidence from preclinical studies conducted at University of Antwerp that in the zQ175DN knock-in mouse model of HD, larger variability and lower effect-sizes are seen with [18F]SynVest-1 than with [11C]UCB-J. In order to ascertain a similar effect size and quantification properties for [18F]SynVest-1 and [11C]UCB-J PET in human HD, both in the premanifest and manifest phase, and to validate simplified measures (such as SUVR with white matter as reference region) and SynVest, this head-to-head fully quantitative study is performed.


Read more »

Study Design


Related Conditions & MeSH terms


Intervention

Other:
[11C]UCB-J
11C-labeled SV2A binding PET radioligand
[18F]SynVest-1
18F-labeled SV2A binding PET radioligand

Locations

Country Name City State
Belgium UZ Leuven Leuven

Sponsors (2)

Lead Sponsor Collaborator
Universitaire Ziekenhuizen KU Leuven CHDI Foundation, Inc.

Country where clinical trial is conducted

Belgium, 

References & Publications (3)

Delva A, Michiels L, Koole M, Van Laere K, Vandenberghe W. Synaptic Damage and Its Clinical Correlates in People With Early Huntington Disease: A PET Study. Neurology. 2022 Jan 4;98(1):e83-e94. doi: 10.1212/WNL.0000000000012969. Epub 2021 Oct 18. — View Citation

Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK, Dhaher R, Matuskey D, Baum E, Holden D, Spencer DD, Mercier J, Hannestad J, Huang Y, Carson RE. Imaging synaptic density in the living human brain. Sci Transl Med. 2016 Jul 20;8(348):348ra96. doi: 10.1126/scitranslmed.aaf6667. — 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

Outcome

Type Measure Description Time frame Safety issue
Primary Vt of [11C]UCB-J and [18F]SynVest-1 in premanifest HD. Changes in total volume of distribution (Vt) are similar for [11C]UCB-J and [18F]SynVest-1 in premanifest HD compared to controls. Order of [18F]SynVest-1 and [11C]UCB-J can be interchanged, maximum difference between scans is 30 days, ideally both are done on the same day. Estimated length of visits in total is +/- 3 hours.
Primary Vt of [11C]UCB-J and [18F]SynVest-1 in manifest HD. Changes in total volume of distribution (Vt) are similar for [11C]UCB-J and [18F]SynVest-1 in manifest HD compared to controls. Order of [18F]SynVest-1 and [11C]UCB-J can be interchanged, maximum difference between scans is 30 days, ideally both are done on the same day. Estimated length of visits in total is +/- 3 hours.
Secondary Variance in Vt within groups for both tracers is similar. The variance in total volume of distribution (Vt) is not statistically significantly different between [11]C-UCB-J and [18]F-SynVest-1 in healthy volunteers, in premanifest and manifest HDGEC. Order of [18F]SynVest-1 and [11C]UCB-J can be interchanged, maximum difference between scans is 30 days, ideally both are done on the same day. Estimated length of visits in total is +/- 3 hours.
Secondary Simplified measures (SUVR) can be used to assess group differences for both tracers. Volume of distribution (Vt) and SUVR of [11C]UCB-J and [18F]SynVest-1 are highly correlated. Order of [18F]SynVest-1 and [11C]UCB-J can be interchanged, maximum difference between scans is 30 days, ideally both are done on the same day. Estimated length of visits in total is +/- 3 hours.
See also
  Status Clinical Trial Phase
Terminated NCT03052712 - Validation and Standardization of a Battery Evaluation of the Socio-emotional Functions in Various Neurological Pathologies N/A
Not yet recruiting NCT04429230 - Non-invasive Brain Stimulation in Huntington's Disease N/A
Recruiting NCT05032196 - Study of WVE-003 in Patients With Huntington's Disease Phase 1/Phase 2
Recruiting NCT03599076 - Wearable Sensors for Quantitative Assessment of Motor Impairment in Huntington's Disease Huntington's Disease
Terminated NCT04617860 - Open-label Extension Study to Evaluate the Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease Phase 1/Phase 2
Completed NCT05748288 - Development of the Virtual Unified Huntington's Disease Rating Scale
Not yet recruiting NCT04370470 - Development of Assessments for Later Stage HD
Recruiting NCT01834053 - Safety and Efficacy of Bone Marrow Derived MNCs for Treatment of Cells for the Treatment of Hunting Tons Chorea. Phase 1/Phase 2
Completed NCT01357681 - Effects of EGCG (Epigallocatechin Gallate) in Huntington's Disease (ETON-Study) Phase 2
Completed NCT01458470 - A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease Phase 2
Completed NCT00980694 - Bioavailability of Ubiquinol in Huntington Disease Phase 1
Completed NCT00146211 - TREND-HD - A Trial of Ethyl-EPA (Miraxion™) in Treating Mild to Moderate Huntington's Disease Phase 3
Recruiting NCT01412125 - Study of Biomarkers That Predict the Evolution of Huntington's Disease N/A
Completed NCT00075140 - Family Health After Predictive Huntington Disease (HD) Testing Phase 3
Recruiting NCT04818060 - Preparing for Prevention of Huntington's Disease (PREVENT-HD)
Active, not recruiting NCT04698551 - NIPD on cffDNA for Triplet Repeat Diseases
Not yet recruiting NCT04301726 - Efficacy of Deutetrabenazine to Control Symptoms of Dysphagia Associated With HD Phase 1
Completed NCT03421327 - Genetic Risk: Whether, When, and How to Tell Adolescents
Recruiting NCT03296176 - Metabolomic Study in Huntington's Disease (METABO-HD) N/A
Recruiting NCT05243017 - Safety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington's Disease Phase 1/Phase 2

External Links