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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04257513
Recruitment Status : Recruiting
First Posted : February 6, 2020
Last Update Posted : February 6, 2020
Sponsor:
Collaborator:
Istituto Di Ricerche Farmacologiche Mario Negri
Information provided by (Responsible Party):
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

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.

Condition or disease Intervention/treatment
Huntington Disease Diagnostic Test: Brain MRI

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.

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Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Innovative Therapeutic Strategy Targeting Neurons With Cholesterol in Huntington Disease: From Preclinical Studies to Clinical Trial Readiness
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2022


Group/Cohort Intervention/treatment
Healthy controls subjects
Subjects without known family history of HD, or tested negative for the HD expansion mutation.
Diagnostic Test: Brain MRI
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.
Diagnostic Test: Brain MRI
Neurological and Cognitive evaluation; Brain MRI

Presymptomatic HD subjects:
Subjects HD gene expansion carriers who not have clinical diagnostic motor features of HD.
Diagnostic Test: Brain MRI
Neurological and Cognitive evaluation; Brain MRI




Primary Outcome Measures :
  1. plasmatic 24OHC levels [ Time Frame: at baseline and after 2-years follow up visit ]
    Changes in plasmatic 24OHC levels measured


Secondary Outcome Measures :
  1. Changes in the score of the Unified Huntington Disease Rating Scale (UHDRS) [ Time Frame: after 2-years follow up visit ]
    The concentration of 24OHC will be correlated with clinical evaluation to the stage of the disease and its progression.

  2. Changes in score at the Digit Symbol Modalities Test (DSMT) [ Time Frame: after 2-years follow up visit ]
    The concentration of 24OHC will be correlated with cognitive evaluation to the stage of the disease and its progression.

  3. Changes in caudate nucleus volume measured at MRI [ Time Frame: after 2-years follow up visit ]
    The concentration of 24OHC will be correlated with Imaging the stage of the disease and its progression.


Biospecimen Retention:   Samples Without DNA
Plasma


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
At least 60 subjects (both males and females) will be enrolled in the study. Eligible participants include healthy controls, people who are in the presymptomatic stage of HD, and people with symptomatic HD at different disease stage (I-III).
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04257513


Contacts
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Contact: Caterina Mariotti, MD +39022394 ext 2269 caterina.mariotti@istituto-besta.it
Contact: Renato Mantegazza, MD +39022394 ext 2321 crc@istituto-besta.it

Locations
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Italy
UOC Genetica Medica e Neurogenetica Recruiting
Milano, Italy, 20133
Contact: Caterina Mariotti, MD    +39022394 ext 2269    caterina.mariotti@istituto-besta.it   
Contact: Lorenzo Nanetti, MD    +39022394 ext 2519    lorenzo.nanetti@istituto-besta.it   
Principal Investigator: Caterina Mariotti, MD         
Sub-Investigator: Lorenzo Nanetti, MD         
Sub-Investigator: Alessia Mongelli, Msc         
Sponsors and Collaborators
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Istituto Di Ricerche Farmacologiche Mario Negri
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Responsible Party: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
ClinicalTrials.gov Identifier: NCT04257513    
Other Study ID Numbers: Chol-HD
First Posted: February 6, 2020    Key Record Dates
Last Update Posted: February 6, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta:
Huntington Disease
Cholesterol
Additional relevant MeSH terms:
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Huntington Disease
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
Cognition Disorders
Neurocognitive Disorders
Mental Disorders