Innovative Imaging and Cognitive BIOmarkers to Predict Huntington's Disease Progression (I2BIO-HD)

Assistance Publique - Hôpitaux de Paris

Status: Enrolling

Conditions: Huntington Disease

Treatments: Radiation: radiotracer injection

Study type: Interventional

Funder types: Other

Identifiers

NCT05808153

2021-004141-20 (EudraCT Number)

APHP210360

Details and patient eligibility

About

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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Symptomatic (MH) and pre-symptomatic (preMH) patients

Experimental group

Description:

* 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

Treatment:

Radiation: radiotracer injection

Age-matched controls (healthy volunteers)

Active Comparator group

Description:

* TFC functional UHDRS score = 13 * TMS engine UHDRS rating \< 6

Treatment:

Radiation: radiotracer injection