Clinical trial NCT04701580: 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
Overall status: COMPLETED
Phase: NA
Conditions: Huntington Disease
Keywords: Huntington Disease
PET
11C-UCB-J
18F-FDG
SV2A
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2021-01-08
Enrollment: 33
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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.
Primary purpose: DIAGNOSTIC

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.


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.

Primary outcomes:
measure: Baseline differences in synaptic density.
timeFrame: Data analysis wel be done when all subjects have undergone the baseline evaluation.
measure: Baseline correlations between clinical scores and regional synaptic density.
timeFrame: Data analysis wel be done when all subjects have undergone the baseline evaluation.
measure: Differences in the rate of decline of synaptic density.
timeFrame: Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.
measure: Correlations between progression of the clinical scores and decline of synaptic density.
timeFrame: Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.
Secondary outcomes:
measure: Baseline differences in cerebral glucose metabolism.
timeFrame: Data analysis wel be done when all subjects have undergone the baseline evaluation.
measure: Baseline correlations between clinical scores and cerebral glucose metabolism.
timeFrame: Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.
measure: Differences in the rate of decline of cerebral glucose metabolism.
timeFrame: Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.
measure: Correlations between progression of the clinical scores and decline of cerebral glucose metabolism in the patient group, after longitudinal follow up of 2 years.
timeFrame: Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation.
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-Brabant
Study officials:
affiliation: UZ Leuven
name: Wim Vandenberghe, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: