Comparison Between [11C]UCB-J and [18F]SynVest-1 PET in HD.
ConditionHuntington Disease
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age20-75
SponsorUniversitaire Ziekenhuizen KU Leuven
About this trial
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 patients 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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Healthy controls (n = 10-20)
Subject is judged to be in good health by the investigator on the basis of medical history, physical examination including vital signs, clinical laboratory test and urinalysis.
No history or evidence of current major neurological, internal or psychiatric disorder, based on the medical assessment as described hereabove and neuropsychological assessment.
In subjects < 60 years of age, an unremarkable structural MRI scan as assessed by expert radiologist. In subjects >= 60 years of age white matter hyperintensities corresponding to a white matter lesion (WML) Fazekas score < 2 on the Age-Related White Matter changes scale are acceptable.
Disqualifiers
Neuropsychiatric diseases; for HD mutation carriers any neuropsychiatric diseases other than HD
Major internal medical diseases
White matter lesion load on FLAIR Fazekas score 2 or higher or other relevant MRI abnormalities
History of alcohol abuse or current alcohol abuse (chronic use of more than 15 units per week) or drug use
Trial design
Design model
Single group
Treatments tested in this trial
[11C]UCB-J PET
Other intervention11C-labeled SV2A binding PET radioligand
[18F]SynVest-1 PET
Other intervention18F-labeled SV2A binding PET radioligand
Treatment groups
35 Participants
are divided into 3 treatment groupsGroup A: Cohort 1 + 2: healthy controlsActive comparator 2 interventions
Group B: Cohort 1: stage 3 manifest HD patientsExperimental treatment 2 interventions
Group C: Cohort 2: stage 2 manifest HD patientsExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Compare Vt of [11C]UCB-J and [18F]SynVest-1 in manifest HD and healthy controls
Assess whether changes in total volume of distribution (Vt) are similar for \[11C\]UCB-J and \[18F\]SynVest-1 in manifest HD compared to healthy controls.
Time frame
A first data analysis will be done when all cohort 1 subjects have undergone evaluations. A go-no-go decision will then be made before proceeding with cohort 2. Data analysis of cohort 2 subjects will follow completion of cohort 2.Secondary outcomes
1
Compare variance in Vt within groups for [11C]UCB-J and [18F]SynVest-1
Compare the variance in total volume of distribution (Vt) between \[11C\]UCB-J and \[18F\]SynVest-1 in healthy volunteers and manifest HD patients.
Time frame
A first data analysis will be done when all cohort 1 subjects have undergone evaluations. A go-no-go decision will then be made before proceeding with cohort 2. Data analysis of cohort 2 subjects will follow completion of cohort 2.2
Compare simplified measures (BPND, SUVR) to assess group differences for [11]C-UCB-J and [18]F-SynVest-1
Compare volume of distribution (Vt), BPND and SUVR between \[11C\]UCB-J and \[18F\]SynVest-1 in HD patients and healthy controls.
Time frame
A first data analysis will be done when all cohort 1 subjects have undergone evaluations. A go-no-go decision will then be made before proceeding with cohort 2. Data analysis of cohort 2 subjects will follow completion of cohort 2.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Universitaire Ziekenhuizen KU Leuven
Lead sponsor
CHDI Foundation, Inc.
Collaborator
Source ClinicalTrials.gov