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

Last updated: November 8, 2024
Sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Overall Status: Completed

Phase

N/A

Condition

Dyskinesias

Treatment

Brain MRI

Clinical Study ID

NCT04257513
Chol-HD
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Symptomatic HD subjects

  1. Age ≥ 18 years

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

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

  4. Stage I or II or III HD, defined as UHDRS Total Functional Capacity (TFC) scoresbetween 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 forHD (CAG expansion ≤ 35 repeats)

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

Exclusion

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

Study Design

Total Participants: 60
Treatment Group(s): 1
Primary Treatment: Brain MRI
Phase:
Study Start date:
October 31, 2019
Estimated Completion Date:
June 02, 2023

Study 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.

Connect with a study center

  • UOC Genetica Medica e Neurogenetica

    Milano, 20133
    Italy

    Site Not Available

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