Synaptic Density and Progression of Huntington's Disease.

NCT04701580 | Completed

• 1 other identifier: s61478
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Huntington Disease

Keywords

Huntington Disease; PET; 11C-UCB-J; 18F-FDG; SV2A

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• Baseline differences in cerebral glucose metabolism.

  Data analysis wel be done when all subjects have undergone the baseline evaluation.

• 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.

• 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.

• 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.

Study Arms (2)

HD patients

EXPERIMENTAL

At baseline and 2-year follow-up

Diagnostic Test: 11C-UCB-J PET-CT; Diagnostic Test: 18F-FDG PET-MR

Healthy controls

ACTIVE COMPARATOR

At baseline and 2-year follow-up

Diagnostic Test: 11C-UCB-J PET-CT; Diagnostic Test: 18F-FDG PET-MR

Interventions

11C-UCB-J PET-CT DIAGNOSTIC_TEST

Positron Emission Tomography (PET) of synaptic vesicle protein 2A (SV2A) using the radioligand 11C-UCB-J.

HD patients; Healthy controls

18F-FDG PET-MR DIAGNOSTIC_TEST

Positron Emission Tomography (PET) of glucose metabolism using the radioligand 18F-FDG, and brain MRI performed simultaneously.

HD patients; Healthy controls

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Wim Vandenberghe, MD, PhD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 8, 2021
• Study Start: January 14, 2020
• Primary Completion: October 5, 2022
• Study Completion: October 5, 2022
• Last Updated: November 3, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)