Synaptic Density and Progression of Huntington's Disease.

Study Overview
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Brief Summary
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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.

Official Title
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Longitudinal Measurement of Synaptic Density to Monitor Progression of Huntington's Disease.

Conditions
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Huntington Disease

Intervention / Treatment
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* Diagnostic Test: 11C-UCB-J PET-CT
* Diagnostic Test: 18F-FDG PET-MR


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HD patients<br>At baseline and 2-year follow-up | Diagnostic Test: 11C-UCB-J PET-CT<br>* Positron Emission Tomography (PET) of synaptic vesicle protein 2A (SV2A) using the radioligand 11C-UCB-J.<br>Diagnostic Test: 18F-FDG PET-MR<br>* Positron Emission Tomography (PET) of glucose metabolism using the radioligand 18F-FDG, and brain MRI performed simultaneously.<br>|
| Active Comparator: Healthy controls<br>At baseline and 2-year follow-up | Diagnostic Test: 11C-UCB-J PET-CT<br>* Positron Emission Tomography (PET) of synaptic vesicle protein 2A (SV2A) using the radioligand 11C-UCB-J.<br>Diagnostic Test: 18F-FDG PET-MR<br>* Positron Emission Tomography (PET) of glucose metabolism using the radioligand 18F-FDG, and brain MRI performed simultaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline differences in synaptic density. | Baseline differences (%) in (regional) synaptic density between patients and controls. | Data analysis wel be done when all subjects have undergone the baseline evaluation. | 
| Baseline correlations between clinical scores and regional synaptic density. | Correlations between clinical scores and regional synaptic density in the patient group at baseline. | Data analysis wel be done when all subjects have undergone the baseline evaluation. | 
| Differences in the rate of decline of synaptic density. | Differences (%) in the rate of decline of synaptic density between patients and controls. | 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. | Correlations between progression of the clinical scores and decline of synaptic density 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline differences in cerebral glucose metabolism. | Baseline differences (%) in (regional) glucose metabolism between patients and controls. | Data analysis wel be done when all subjects have undergone the baseline evaluation. | 
| Baseline correlations between clinical scores and cerebral glucose metabolism. | Correlations between clinical scores and cerebral glucose metabolism in the patient group at baseline. | Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation. | 
| Differences in the rate of decline of cerebral glucose metabolism. | Differences (%) in the rate of decline in cerebral glucose metabolism between patients and controls. | 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. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Huntington Disease, PET, 11C-UCB-J, 18F-FDG, SV2A