Huntington Disease
Conditions
Keywords
Huntington's disease, Biomarkers, Cognition, Disease progression, Imaging
Brief summary
Intro Huntington's disease (HD) patients suffer from motor, cognitive and behavioral impairments, with heterogeneous phenotypes and variable time course. This leads to a high variance of HD markers, none of which is currently sensitive enough to 1) measure disease progression from small cohort data, 2) predict disease entry in carriers of the HD mutation (during the prodromal phase or in patients considered asymptomatic: pre-HD patients), and 3) measure a significant evolution of the state of pre-HD patients over a time window compatible with the realization of clinical trials (about 2/3 years). Moreover, the markers of HD do not allow a fine stratification of the patients. Hypothesis/Objective Our objectives are 1) to evaluate the sensitivity of new markers and assessment tools for symptomatic (HD) and presymptomatic (pre-HD) patients, 2) to define a model of disease progression, and 3) to establish an enrichment strategy to improve patient selection for future therapeutic trials. Method We will evaluate newly developed cognitive tests, multimodal imaging techniques, biological markers and use innovative statistical approaches. We will follow 60 patients with the mutation responsible for MH (40 presymptomatic pre-MH patients, 20 symptomatic MH patients) and 20 healthy volunteers (controls) over a 24-month period.
Interventions
RADIATIONradiotracer injection
MRI with radiotracer injection
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Model description: Identification, evaluation and validation of new clinical, biological and imaging biomarkers (MRI without contrast product and PET with intravenous administration of a radiotracer) on a prospective cohort of carriers of the mutation responsible for Huntington's disease and healthy volunteers.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* For all participants: * Age ≥18 years and ≤65 years * Information and collection of written consent * Affiliation with a social security plan, beneficiary or beneficiary's right * Healthy controls * UHDRS functional score TFC = 13 * Motor UHDRS score TMS \< 6 With no known genetic disease and no direct relationship to an HD patient or family ancestors carrying the HD mutation (or knowing their genetic status with CAG \< 36). * Manifest carriers * Number of GACs ≥ 40 * CAP score ≥ 250 * 10 ≤ TFC ≤ 13 * TMS \>5 if TFC=13 * Diagnostic confidence level =4 * Age of onset of disease \> 20 years * Patients physically able to sign consent * Premanifest carriers * Number of GACs ≥ 40 * CAP score ≥250 * CFT = 13 * TMS \< 6 * Patients physically able to sign consent
Exclusion criteria
* Participant under guardianship or curatorship * Neurological or psychiatric disorder unrelated to HD * Intercurrent illness that may impact participant's performance * Chronic progressive neurological disease * Claustrophobia * Brain injury unrelated to HD * Pacemaker, intracorporeal metal, intracerebral clip, any metallic foreign body: implantable cardiac electronic device such as pacemakers, implantable cardioverter defibrillators etc., metallic intraocular foreign bodies, implantable neurostimulation systems, cochlear implants/ear implants, drug infusion pumps (insulin administration, analgesic drugs), or chemotherapy pumps): if possible, the patient should remove the device. * Catheters with metal components (Swan-Ganz catheter), metal fragments such as bullets, shotgun pellets and metal shrapnel, cerebral artery aneurysm clips, magnetic dental implants, tissue expander, artificial limb, hearing aid, piercing such as pacemaker, * Known hypersensitivity to the radiopharmaceutical preparation (excipients in the radiopharmaceutical preparation) * Pregnant or breastfeeding woman * Person under state medical aid * Person deprived of liberty * Person participating or having participated in an interventional study for less than 3 months or without time limit in a trial of neural transplants or gene therapy. * Person participating or having participated in a research protocol with a radiopharmaceutical injection for less than 12 months. * Neurological or psychiatric disorder unrelated to HD * Intercurrent disease that may impact participant's performance * Chronic progressive neurological disease * Claustrophobia * Brain injury unrelated to HD * Pacemaker, intracorporeal metal, intracerebral clip * Pregnant, breastfeeding or wanting to procreate during participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Genetic markers | Visit Month 0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| cognitive tests | Visits Month 0, Month 1, Month 12, Month 24 | Cognitive scores - Neurological scores- Psychiatric scores |
| biological markers | Visits Month 0, Month 1, Month 12, Month 24 | Neuroinflammation markers in blood - Neurodegeneration markers in blood |
| multimodal imaging techniques | Visits Month 0, Month 12, Month 24 | MRI |
Countries
France
Contacts
Primary ContactAnne-Catherine BACHOUD-LEVI, PhD
Outcome results
None listed