Comparison Between [11C]UCB-J and [18F]SynVest-1 PET in HD.

December 15, 2023 updated by: Universitaire Ziekenhuizen KU Leuven

Direct Quantitative Comparison Between [11C]UCB-J and [18F]SynVest-1 PET as Markers for Synaptic Density in Premanifest and Manifest 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.

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Wim Vandenberghe, MD PhD

Study Contact Backup

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • UZ Leuven

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

10 premanifest HD mutation carriers 10 manifest (stage 1 or 2) HD mutation carriers 10 age- and gender matched healthy controls

Description

Inclusion Criteria:

  1. Healthy controls

    • 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.

  2. HD mutation carriers

    • CAG repeat expansion in HTT ≥ 40.

      * For premanifest HD mutation carriers (n = 10):

    • No clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score < 4.

      * For early manifest HD patients (n = 10):

    • Clinical diagnostic motor features of HD, defined as UHDRS Diagnostic Confidence Score = 4.
    • Shoulson-Fahn stage 1-2

Exclusion Criteria:

  • Neuropsychiatric diseases, for HD mutation carriers: 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Healthy controls
Other: [11C]UCB-J
11C-labeled SV2A binding PET radioligand
Other: [18F]SynVest-1
18F-labeled SV2A binding PET radioligand
Premanifest HD mutation carriers
  • HTT CAG repeat length ≥ 40
  • UHDRS Diagnostic confidence level < 4
Other: [11C]UCB-J
11C-labeled SV2A binding PET radioligand
Other: [18F]SynVest-1
18F-labeled SV2A binding PET radioligand
Manifest HD mutation carriers
  • HTT CAG repeat length ≥ 40
  • UHDRS Diagnostic confidence level = 4
  • Shoulson-Fahn stage 1-2
Other: [11C]UCB-J
11C-labeled SV2A binding PET radioligand
Other: [18F]SynVest-1
18F-labeled SV2A binding PET radioligand

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vt of [11C]UCB-J and [18F]SynVest-1 in premanifest HD.
Time Frame: 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.
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.
Vt of [11C]UCB-J and [18F]SynVest-1 in manifest HD.
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Variance in Vt within groups for both tracers is similar.
Time Frame: 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.
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.
Simplified measures (SUVR) can be used to assess group differences for both tracers.
Time Frame: 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitaire Ziekenhuizen KU Leuven

Collaborators

CHDI Foundation, Inc.

Investigators

  • Principal Investigator: Koen Van Laere, MD PhD DSc, UZ/KU Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

April 28, 2022

First Submitted That Met QC Criteria

April 28, 2022

First Posted (Actual)

May 4, 2022

Study Record Updates

Last Update Posted (Estimated)

December 18, 2023

Last Update Submitted That Met QC Criteria

December 15, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S66610

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

To be determined

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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