Clinical Study to Monitor Plasma Levels of 24OHC in Subject with HD

NCT ID: NCT04257513

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-10-31
• Study Completion Date: 2023-06-02

Brief Summary

A 2-year clinical longitudinal study to measure plasma concentrations of 24S-hydroxycholesterol, a brain-derived cholesterol catabolite, in subjects with Huntington disease, from the presymptomatic to the symptomatic stages.

Detailed Description

In cross-sectional studies, the plasma level of brain-derived 24S-hydroxycholesterol (24OHC) has been found to be significantly diminished in HD patients from the first stages of the disease. Furthermore, in HD gene-positive pre-symptomatic (pre-HD) the plasma levels can predict the development of motor signs of disease in subjects closer to onset, better than in subjects far from onset. These data suggest that circulating 24OHC might be a candidate biomarker for phenotypic conversion and for disease progression in different stages of the disease.

Detailed neurological, cognitive and imaging data and blood samples will be collected at baseline, and after two years to investigate the rate of changes along the longitudinal study. Isotope dilution mass spectrometry (assay performed at Istituto di Ricerche Farmacologiche Mario Negri IRCCS) will be used to measure the plasma levels of brain-derived 24OHC and other sterols reflecting peripheral cholesterol synthesis. The investigators expect to establish whether changes in plasma 24OHC mark disease progression and, eventually, phenoconversion from pre-symptomatic to symptomatic stages in combination with clinical, cognitive and imaging parameters.

Conditions

Huntington Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Healthy controls subjects

Subjects without known family history of HD, or tested negative for the HD expansion mutation.

Brain MRI

Intervention Type: DIAGNOSTIC_TEST

Neurological and Cognitive evaluation; Brain MRI

Symptomatic HD subjects

Subjects HD gene expansion carriers who have clinical diagnostic motor symptoms of defined HD, and disease stage I to III.

Brain MRI

Intervention Type: DIAGNOSTIC_TEST

Neurological and Cognitive evaluation; Brain MRI

Presymptomatic HD subjects:

Subjects HD gene expansion carriers who not have clinical diagnostic motor features of HD.

Brain MRI

Intervention Type: DIAGNOSTIC_TEST

Neurological and Cognitive evaluation; Brain MRI

Interventions

Brain MRI

Neurological and Cognitive evaluation; Brain MRI

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

Symptomatic HD subjects

1. Age ≥ 18 years

2. Known family history of HD and genetically confirmed disease by direct DNA test (CAG expansion > 35 repeats)

3. Clinical diagnostic motor features of HD, defined as score> 5 at the motor Unified Huntington Disease Rating Scale (mUHDRS)

4. Stage I or II or III HD, defined as UHDRS Total Functional Capacity (TFC) scores between 3 and 13 inclusive (Marder, 2000)

Presymptomatic HD subjects

1. Age ≥ 18 years

2. Known family history of HD and genetically confirmed mutation by direct DNA test (CAG expansion > 35 repeats)

3. Absence of clinical motor features of HD, defined as mUHDRS rating scale ≤ 5

Healthy Subjects

1. Age ≥ 18 years

2. Absence of known family history of HD or genetically confirmed negative DNA test for HD (CAG expansion ≤ 35 repeats)

3. Absence of clinical motor features of HD, defined as mUHDRS rating scale ≤ 5

Exclusion Criteria

1. Participation in clinical pharmacological trials

2. Inability to undergo and tolerate MRI scans (e.g. claustrophobia, severe chorea, MRI-incompatible intrauterine devices, metal implants, ect)

3. Inability or unwillingness to undertake any of the study procedures

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Di Ricerche Farmacologiche Mario Negri

OTHER

Sponsor Role: collaborator

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UOC Genetica Medica e Neurogenetica

Milan, Milano, Italy

Countries

Italy

Other Identifiers

Chol-HD

Identifier Type: -

Identifier Source: org_study_id