Huntington DiseaseNCT05360082
Comparison Between [11C]UCB-J and [18F]SynVest-1 PET in HD.
A study testing [11C]UCB-J PET and [18F]SynVest-1 PET in people with Huntington Disease, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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… Read more about this study
- Who is it for?
- Ages 20 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Huntington Disease
- What is being tested?
- [11C]UCB-J PET and [18F]SynVest-1 PET
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteBelgium
- Study dates
- 18 Nov 2024to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
- HD-ISS stage 3 HD mutation carriers (n = 10)
- HTT CAG repeat expansion 40 - 50
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- stage 3 as determined by the HD-ISS staging criteria
- UHDRS TFC >/= 10
- HD-ISS stage 2 HD mutation carriers (n = 10)
- HTT CAG repeat expansion 40 - 50
- stage 2 as determined by the HD-ISS staging criteria
- PIN score 0.47 - 1.84
Who cannot join
- 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
- Contraindications for MR
- Subject suffers from claustrophobia or cannot tolerate confinement during PET-MRI scanning procedures; subject cannot lie still for 30 minutes inside the scanner.
Show all 13Show fewer
- Subject is unwilling to avoid unusual, unaccustomed, or strenuous physical activity (i.e., weightlifting, running, bicycling) from the time of the pre-study visit until the end of scanning.
- Subject does not understand the study procedures or does not have a guardian who understands the study procedures.
- Subject (or guardian) is unwilling or unable to perform all of the study procedures or is considered unsuitable in any way by the principal investigator.
- Subject is on anticoagulant therapy.
- Subject is pregnant (according to Ulti Med hCG urine test) or breastfeeding.
- Subject is a woman of childbearing potential who does not agree to apply appropriate contraception methods during study participation and continues to do so for at least 6 months after study completion.
- Subject is a man with a pregnant or non-pregnant WOCBP partner, who does not agree to use a condom and continue to do so until 90 days after study completion. In addition, the non-pregnant WOCBP partner should use a highly effective method of contraception.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Wim Vandenberghe, MD, PhD contact
Belgium1 site, 1 recruiting
- Recruiting
UZ Leuven
Leuven, 3000
Koen Van Laere, MD, PhD, DSc, +3216343714, koen.vanlaere@uzleuven.be
Wim Vandenberghe, MD, PhD
About this study
Official title: Direct Quantitative Comparison Between [11C]UCB-J and [18F]SynVest-1 PET as Markers for Synaptic Density in Huntington's Disease.
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.
Read more
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.
- Conditions
- Huntington Disease
- Being tested
- [11C]UCB-J PET, [18F]SynVest-1 PET
- Keywords
- PET, SV2A, Huntington disease, synaptic density
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[11C]UCB-J PETOther
11C-labeled SV2A binding PET radioligand
[18F]SynVest-1 PETOther
18F-labeled SV2A binding PET radioligand
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 + 2: healthy controls | Active comparator | Age -and sex matched to HD patients (to stage 3 HD patients for cohort 1 and to stage 2 HD patients for cohort 2) Receives: Other: [11C]UCB-J PET; Other: [18F]SynVest-1 PET |
| Cohort 1: stage 3 manifest HD patients | Experimental | * HTT CAG repeat expansion 40 - 50;
* stage 3 as determined by the HD-ISS staging criteria;
* UHDRS TFC >/= 10. Receives: Other: [11C]UCB-J PET; Other: [18F]SynVest-1 PET |
| Cohort 2: stage 2 manifest HD patients | Experimental | * HTT CAG repeat expansion 40 - 50;
* stage 2 as determined by the HD-ISS criteria;
* PIN score 0.47 to 1.84. Receives: Other: [11C]UCB-J PET; Other: [18F]SynVest-1 PET |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (2)
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.
Measured: 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.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2022
- Study start18 Nov 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Huntington DiseaseStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- CHDI Foundation, Inc.
- Responsible party
- Sponsor
- Investigators
- Koen Van Laere, MD, PhD, DSc, Principal investigator, UZ/KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05360082
- Sponsor's protocol ID
- S66610
- Status last verified
- Dec 2024
- First submitted
- 28 Apr 2022
- Last updated
- 30 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: To be determined
Publications
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.
PubMed 34663644Finnema 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.
PubMed 27440727Naganawa 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.
PubMed 32859701Everix L, Zajicek F, Eetveldt AV, Liu L, Bard J, Staelens S, Bertoglio D. Assessment of changes in synaptic density in the zQ175DN mouse model of Huntington's disease: a [18F]SynVesT-1 study. Neuroimage Clin. 2025;46:103800. doi: 10.1016/j.nicl.2025.103800. Epub 2025 May 10.
PubMed 40381377
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Direct Quantitative Comparison Between [11C]UCB-J and [18F]SynVest-1 PET as Markers for Synaptic Density in Huntington's Disease.
- ClinicalTrials.gov ID
- NCT05360082
- Acronym / sponsor ID
- S66610
- Conditions
- Huntington Disease
- Keywords
- PET, SV2A, Huntington disease, synaptic density
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- CHDI Foundation, Inc.
- Study start
- 18 Nov 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 4 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 + 2: healthy controls | Active comparator | Other: [11C]UCB-J PET, Other: [18F]SynVest-1 PETAge -and sex matched to HD patients (to stage 3 HD patients for cohort 1 and to stage 2 HD patients for cohort 2) |
| Cohort 1: stage 3 manifest HD patients | Experimental | Other: [11C]UCB-J PET, Other: [18F]SynVest-1 PET* HTT CAG repeat expansion 40 - 50; * stage 3 as determined by the HD-ISS staging criteria; * UHDRS TFC >/= 10. |
| Cohort 2: stage 2 manifest HD patients | Experimental | Other: [11C]UCB-J PET, Other: [18F]SynVest-1 PET* HTT CAG repeat expansion 40 - 50; * stage 2 as determined by the HD-ISS criteria; * PIN score 0.47 to 1.84. |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Healthy controls (n = 10-20)
- HD-ISS stage 3 HD mutation carriers (n = 10)
- HD-ISS stage 2 HD mutation carriers (n = 10)
Key exclusion criteria (13 listed)
- 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
- Contraindications for MR
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [11C]UCB-J PET11C-labeled SV2A binding PET radioligand | Other | Cohort 1 + 2: healthy controls, Cohort 1: stage 3 manifest HD patients, Cohort 2: stage 2 manifest HD patients |
| [18F]SynVest-1 PET18F-labeled SV2A binding PET radioligand | Other | Cohort 1 + 2: healthy controls, Cohort 1: stage 3 manifest HD patients, Cohort 2: stage 2 manifest HD patients |
Primary outcome
Compare Vt of [11C]UCB-J and [18F]SynVest-1 in manifest HD 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.
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.
2 secondary outcomes
Compare variance in Vt within groups for [11C]UCB-J and [18F]SynVest-1
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.
Compare simplified measures (BPND, SUVR) to assess group differences for [11]C-UCB-J and [18]F-SynVest-1
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2025.
- Background: PubMed 34663644Delva 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.
- Background: PubMed 27440727Finnema 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.
- Background: PubMed 32859701Naganawa 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.
- Derived from this study: PubMed 40381377Everix L, Zajicek F, Eetveldt AV, Liu L, Bard J, Staelens S, Bertoglio D. Assessment of changes in synaptic density in the zQ175DN mouse model of Huntington's disease: a [18F]SynVesT-1 study. Neuroimage Clin. 2025;46:103800. doi: 10.1016/j.nicl.2025.103800. Epub 2025 May 10.
- CHDI Foundation, Inc.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided. To be determined
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Wim Vandenberghe, MD, PhD contact
Koen Van Laere, MD, PhD, DSc principal investigator
UZ/KU Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing [11C]UCB-J PET and [18F]SynVest-1 PET in people with Huntington Disease, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Koen Van Laere, MD, PhD, DSc (+3216343714, koen.vanlaere@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare Vt of [11C]UCB-J and [18F]SynVest-1 in manifest HD 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05360082, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2025.