Synaptic Density and Progression of Huntington's Disease.

Not Applicable

Completed

• Conditions: Huntington Disease
• Interventions: Diagnostic Test: 11C-UCB-J PET-CT; Diagnostic Test: 18F-FDG PET-MR

• Registration Number: NCT04701580
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-14
• Study First Submitted: 2021-01-05
• Study First Submitted QC: 2021-01-05
• Study First Posted: 2021-01-08
• Primary Completion: 2022-10-05
• Study Completion: 2022-10-05
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-02
• Last Update Posted: 2022-11-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HD patients	18F-FDG PET-MR	At baseline and 2-year follow-up
HD patients	11C-UCB-J PET-CT	At baseline and 2-year follow-up
Healthy controls	11C-UCB-J PET-CT	At baseline and 2-year follow-up
Healthy controls	18F-FDG PET-MR	At baseline and 2-year follow-up

Primary Outcome Measures

Name	Time	Method
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 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.
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.
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.

Trial Locations

Locations (1)

UZ Leuven; 🇧🇪 Leuven, Vlaams-Brabant, Belgium