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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05808153

Collaborator

(none)

Enrollment

Arms

46.1

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Huntington Disease	Radiation: radiotracer injection	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

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.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)

Primary Purpose:

Other

Official Title:

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

Anticipated Study Start Date :

Apr 2, 2023

Anticipated Primary Completion Date :

Apr 2, 2025

Anticipated Study Completion Date :

Feb 2, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Symptomatic (MH) and pre-symptomatic (preMH) patients 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 MRI with radiotracer injection
Active Comparator: Age-matched controls (healthy volunteers) TFC functional UHDRS score = 13 TMS engine UHDRS rating < 6	Radiation: radiotracer injection MRI with radiotracer injection

Arm

Intervention/Treatment

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

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

MRI with radiotracer injection

Active Comparator: Age-matched controls (healthy volunteers)

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

Radiation: radiotracer injection

MRI with radiotracer injection

Outcome Measures

Primary Outcome Measures

Genetic markers [Visit Month 0]

Secondary Outcome Measures

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
multimodal imaging techniques [Visits Month 0, Month 24]
PET/MRI

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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.