Synaptic Density and Progression of Huntington's Disease.
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HD patients At baseline and 2-year follow-up |
Diagnostic Test: 11C-UCB-J PET-CT
Positron Emission Tomography (PET) of synaptic vesicle protein 2A (SV2A) using the radioligand 11C-UCB-J.
Diagnostic Test: 18F-FDG PET-MR
Positron Emission Tomography (PET) of glucose metabolism using the radioligand 18F-FDG, and brain MRI performed simultaneously.
|
| Active Comparator: Healthy controls At baseline and 2-year follow-up |
Diagnostic Test: 11C-UCB-J PET-CT
Positron Emission Tomography (PET) of synaptic vesicle protein 2A (SV2A) using the radioligand 11C-UCB-J.
Diagnostic Test: 18F-FDG PET-MR
Positron Emission Tomography (PET) of glucose metabolism using the radioligand 18F-FDG, and brain MRI performed simultaneously.
|
Outcome Measures
Primary Outcome Measures
- Baseline differences in synaptic density. [Data analysis wel be done when all subjects have undergone the baseline evaluation.]
Baseline differences (%) in (regional) synaptic density between patients and controls.
- Baseline correlations between clinical scores and regional synaptic density. [Data analysis wel be done when all subjects have undergone the baseline evaluation.]
Correlations between clinical scores and regional synaptic density in the patient group at baseline.
- Differences in the rate of decline of synaptic density. [Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.]
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. [Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.]
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. [Data analysis wel be done when all subjects have undergone the baseline evaluation.]
Baseline differences (%) in (regional) glucose metabolism between patients and controls.
- Baseline correlations between clinical scores and cerebral glucose metabolism. [Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.]
Correlations between clinical scores and cerebral glucose metabolism in the patient group at baseline.
- Differences in the rate of decline of cerebral glucose metabolism. [Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.]
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. [Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.]
Correlations between progression of the clinical scores and decline of cerebral glucose metabolism in the patient group, after longitudinal follow up of 2 years.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 20-75 years.
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Capacity to understand the informed consent form.
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For HD group: CAG repeat expansion in HTT ≥ 40.
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Premanifest HD mutation carriers:
- No clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score < 4.
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Early manifest HD patients:
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Clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score = 4.
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UHDRS-TFC score 7 or higher (Shoulson-Fahn stage 1 and 2).
Exclusion Criteria:
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neuropsychiatric diseases other than HD
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major internal medical diseases
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white matter lesion load on FLAIR Fazekas score 2 or higher or other relevant MRI abnormalities
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history of alcohol abuse or current alcohol abuse (chronic use of more than 15 units per week) or drug abuse
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contraindications for MR
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pregnancy
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previous participation in other research studies involving ionizing radiation with >1 mSv in the previous 12 months.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UZ Leuven | Leuven | Vlaams-Brabant | Belgium | 3000 |
Sponsors and Collaborators
- Universitaire Ziekenhuizen Leuven
Investigators
- Principal Investigator: Wim Vandenberghe, MD, PhD, UZ Leuven
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- s61478