Huntington Disease
Conditions
Keywords
Huntington Disease, PET, 11C-UCB-J, 18F-FDG, SV2A
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.
Interventions
DIAGNOSTIC_TEST11C-UCB-J PET-CT
Positron Emission Tomography (PET) of synaptic vesicle protein 2A (SV2A) using the radioligand 11C-UCB-J.
DIAGNOSTIC_TEST18F-FDG PET-MR
Positron Emission Tomography (PET) of glucose metabolism using the radioligand 18F-FDG, and brain MRI performed simultaneously.
Sponsors
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Belgium
Outcome results
None listed