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

NCT05808153 | Recruiting DMC

• 2 other identifiers: APHP2103602021-004141-20
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Huntington Disease

Keywords

Huntington's disease; Biomarkers; Cognition; Disease progression; Imaging

Outcome Measures

Primary Outcomes (1)

• Genetic markers

  Visit Month 0

Secondary Outcomes (4)

• cognitive tests

  Visits Month 0, Month 1, Month 12, Month 24

• biological markers

  Visits Month 0, Month 1, Month 12, Month 24

• multimodal imaging techniques

  Visits Month 0, Month 12, Month 24

• multimodal imaging techniques

  Visits Month 0, Month 24

Study Arms (2)

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

EXPERIMENTAL

* 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

Age-matched controls (healthy volunteers)

ACTIVE COMPARATOR

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

Radiation: radiotracer injection

Interventions

radiotracer injection RADIATION

MRI with radiotracer injection

Age-matched controls (healthy volunteers); Symptomatic (MH) and pre-symptomatic (preMH) patients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ≤ TFC ≤ 13
• TMS \>5 if TFC=13
• Diagnostic confidence level =4
• Age of onset of disease \> 20 years
• Patients physically able to sign consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hopital Henri MONDOR

Créteil, Île-de-France Region, 94000, France

RECRUITING

MeSH Terms

Conditions

Huntington Disease; Disease Progression

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Anne-Catherine BACHOUD-LEVI, PhD

CONTACT

(+33)1 49 81 23 10; anne-catherine.bachoud-levi@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: April 11, 2023
• Study Start: March 21, 2024
• Primary Completion: April 2, 2025
• Study Completion (Estimated): February 2, 2027
• Last Updated: May 7, 2024

Record last verified: 2024-01

Locations

FR (1)