Clinical Study to Monitor Plasma Levels of 24OHC in Subject with HD (Chol-HD)

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

Status: Completed

Conditions: Huntington Disease

Treatments: Diagnostic Test: Brain MRI

Study type: Observational

Funder types: Other

Identifiers

NCT04257513

Chol-HD

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

60 participants in 3 patient groups

Healthy controls subjects

Description:

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

Treatment:

Diagnostic Test: Brain MRI

Symptomatic HD subjects

Description:

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

Treatment:

Diagnostic Test: Brain MRI

Presymptomatic HD subjects:

Description:

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

Treatment:

Diagnostic Test: Brain MRI