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Synaptic Density and Progression of Huntington's Disease.

Primary Purpose

Huntington Disease

Status
Completed
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
11C-UCB-J PET-CT
18F-FDG PET-MR
Sponsored by
Universitaire Ziekenhuizen KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Huntington Disease focused on measuring Huntington Disease, PET, 11C-UCB-J, 18F-FDG, SV2A

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Age 20-75 years.
  • Capacity to understand the informed consent form.
  • For HD group: CAG repeat expansion in HTT ≥ 40.

  • Premanifest HD mutation carriers:

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

  • Early manifest HD patients:

    • Clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score = 4.
    • UHDRS-TFC score 7 or higher (Shoulson-Fahn stage 1 and 2).

Exclusion Criteria:

  • 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 abuse
  • contraindications for MR
  • pregnancy
  • previous participation in other research studies involving ionizing radiation with >1 mSv in the previous 12 months.

Sites / Locations

  • UZ Leuven

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

HD patients

Healthy controls

Arm Description

At baseline and 2-year follow-up

At baseline and 2-year follow-up

Outcomes

Primary Outcome Measures

Baseline differences in synaptic density.
Baseline differences (%) in (regional) synaptic density between patients and controls.
Baseline correlations between clinical scores and regional synaptic density.
Correlations between clinical scores and regional synaptic density in the patient group at baseline.
Differences in the rate of decline of synaptic density.
Differences (%) in the rate of decline of synaptic density between patients and controls.
Correlations between progression of the clinical scores and decline of synaptic density.
Correlations between progression of the clinical scores and decline of synaptic density in the patient group, after longitudinal follow up of 2 years.

Secondary Outcome Measures

Baseline differences in cerebral glucose metabolism.
Baseline differences (%) in (regional) glucose metabolism between patients and controls.
Baseline correlations between clinical scores and cerebral glucose metabolism.
Correlations between clinical scores and cerebral glucose metabolism in the patient group at baseline.
Differences in the rate of decline of cerebral glucose metabolism.
Differences (%) in the rate of decline in cerebral glucose metabolism between patients and controls.
Correlations between progression of the clinical scores and decline of cerebral glucose metabolism in the patient group, after longitudinal follow up of 2 years.
Correlations between progression of the clinical scores and decline of cerebral glucose metabolism in the patient group, after longitudinal follow up of 2 years.

Full Information

First Posted
January 5, 2021
Last Updated
November 2, 2022
Sponsor
Universitaire Ziekenhuizen KU Leuven
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1. Study Identification

Unique Protocol Identification Number
NCT04701580
Brief Title
Synaptic Density and Progression of Huntington's Disease.
Official Title
Longitudinal Measurement of Synaptic Density to Monitor Progression of Huntington's Disease.
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
January 14, 2020 (Actual)
Primary Completion Date
October 5, 2022 (Actual)
Study Completion Date
October 5, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
AIM: To assess synaptic density and to investigate the potential relationship of regional synaptic loss with motor and non-motor symptoms and with disease progression in the human brain in vivo in patients with HD. DESIGN: The investigators will include 20 HD mutations carriers and 15 healthy controls. All subjects will undergo a clinical examination, with comprehensive assessment of motor and non-motor symptoms, and imaging evaluation consisting of 11C-UCB-J PET-CT and 18F-FDG PET-MR at baseline and after 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington Disease
Keywords
Huntington Disease, PET, 11C-UCB-J, 18F-FDG, SV2A

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Longitudinal study design (2 years follow up) where results of SV2A PET/CT, FDG PET/MR and clinical rating scales are compared between HD patients and healthy controls.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HD patients
Arm Type
Experimental
Arm Description
At baseline and 2-year follow-up
Arm Title
Healthy controls
Arm Type
Active Comparator
Arm Description
At baseline and 2-year follow-up
Intervention Type
Diagnostic Test
Intervention Name(s)
11C-UCB-J PET-CT
Intervention Description
Positron Emission Tomography (PET) of synaptic vesicle protein 2A (SV2A) using the radioligand 11C-UCB-J.
Intervention Type
Diagnostic Test
Intervention Name(s)
18F-FDG PET-MR
Intervention Description
Positron Emission Tomography (PET) of glucose metabolism using the radioligand 18F-FDG, and brain MRI performed simultaneously.
Primary Outcome Measure Information:
Title
Baseline differences in synaptic density.
Description
Baseline differences (%) in (regional) synaptic density between patients and controls.
Time Frame
Data analysis wel be done when all subjects have undergone the baseline evaluation.
Title
Baseline correlations between clinical scores and regional synaptic density.
Description
Correlations between clinical scores and regional synaptic density in the patient group at baseline.
Time Frame
Data analysis wel be done when all subjects have undergone the baseline evaluation.
Title
Differences in the rate of decline of synaptic density.
Description
Differences (%) in the rate of decline of synaptic density between patients and controls.
Time Frame
Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.
Title
Correlations between progression of the clinical scores and decline of synaptic density.
Description
Correlations between progression of the clinical scores and decline of synaptic density in the patient group, after longitudinal follow up of 2 years.
Time Frame
Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.
Secondary Outcome Measure Information:
Title
Baseline differences in cerebral glucose metabolism.
Description
Baseline differences (%) in (regional) glucose metabolism between patients and controls.
Time Frame
Data analysis wel be done when all subjects have undergone the baseline evaluation.
Title
Baseline correlations between clinical scores and cerebral glucose metabolism.
Description
Correlations between clinical scores and cerebral glucose metabolism in the patient group at baseline.
Time Frame
Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.
Title
Differences in the rate of decline of cerebral glucose metabolism.
Description
Differences (%) in the rate of decline in cerebral glucose metabolism between patients and controls.
Time Frame
Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.
Title
Correlations between progression of the clinical scores and decline of cerebral glucose metabolism in the patient group, after longitudinal follow up of 2 years.
Description
Correlations between progression of the clinical scores and decline of cerebral glucose metabolism in the patient group, after longitudinal follow up of 2 years.
Time Frame
Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age 20-75 years. Capacity to understand the informed consent form. For HD group: CAG repeat expansion in HTT ≥ 40. Premanifest HD mutation carriers: * No clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score < 4. Early manifest HD patients: Clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score = 4. UHDRS-TFC score 7 or higher (Shoulson-Fahn stage 1 and 2). Exclusion Criteria: 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 abuse contraindications for MR pregnancy previous participation in other research studies involving ionizing radiation with >1 mSv in the previous 12 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wim Vandenberghe, MD, PhD
Organizational Affiliation
UZ Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Leuven
City
Leuven
State/Province
Vlaams-Brabant
ZIP/Postal Code
3000
Country
Belgium

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Needs to be decided.

Learn more about this trial

Synaptic Density and Progression of Huntington's Disease.

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