Innovative Imaging and Cognitive BIOmarkers to Predict Huntington's Disease Progression

Study Overview
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Brief Summary
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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.

Official Title
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Innovative Imaging and Cognitive BIOmarkers to Predict Huntington's Disease Progression

Conditions
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Huntington Disease

Intervention / Treatment
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* Radiation: radiotracer injection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Symptomatic (MH) and pre-symptomatic (preMH) patients<br>Number of GAC ≥ 40 GAP score ≥ 250 10 ≤ TFC ≤ 13 TMS >5 if TFC=13 Diagnostic confidence level =4 Age onset of the disease > 20 years Patients in physical capacity to sign the consent | Radiation: radiotracer injection<br>* MRI with radiotracer injection<br>|
| Active Comparator: Age-matched controls (healthy volunteers)<br>TFC functional UHDRS score = 13 TMS engine UHDRS rating < 6 | Radiation: radiotracer injection<br>* MRI with radiotracer injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic markers |  | Visit Month 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cognitive tests | Cognitive scores - Neurological scores- Psychiatric scores | Visits Month 0, Month 1, Month 12, Month 24 | 
| biological markers | Neuroinflammation markers in blood - Neurodegeneration markers in blood | Visits Month 0, Month 1, Month 12, Month 24 | 
| multimodal imaging techniques | MRI | Visits Month 0, Month 12, Month 24 | 
| multimodal imaging techniques | PET/MRI | Visits Month 0, Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imaging, Huntington's disease, Biomarkers, Cognition, Disease progression