Decoding Presymptomatic White Matter Changes in Huntington Disease (Win-HD)

WIN-HD is a monocentric longitudinal study comparing premanifest Huntingtin (HTT) mutation carriers and non HTT mutation carriers to determine that white-matter atrophy occurs far earlier than clinical onset in HD using Diffusion-weighted Nuclear Magnetic Resonance (N spectroscopy (DWS) and Diffusion Tensor Imaging (DTI).

The investigators will recruit up to 20 premanifest HTT mutation carriers (15 completed) and up to 20 non HTT mutation carriers (15 completed). It is important to have those 2 populations in order to compare our results and determine if there are significant white-matter changes far from the onset of HD. Therefore, non HTT mutation carriers will be age and gender matched to premanifest HTT mutation carriers.

In order to test the hypothesis, the study has 2 visits with a year interval.

This study is based on 4 principal criteria:

1. Imaging criteria
2. Clinical and neurological criteria
3. Psychological criteria
4. Behavioral criteria

Study Overview

• Status: Completed
• Conditions: Huntington Disease; White Matter Alterations
• Intervention / Treatment: Other: Brain imaging; Other: Neurological assessments; Behavioral: Psychological assessments; Behavioral: Behavioural assessments

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 750013
    • Brain and Spine Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For presymptomatic individuals:

  • Genetic test available with CAG (Cytosine-Adenine-Guanine) repeat length > 36 in HTT gene
  • UHDRS score <5
  • Burden score <250

• For controls:

  - Genetic test available with CAG repeat length ≤ 36 in HTT gene

• Common inclusion criteria for presymptomatic individuals and controls (age-matched and gender-matched with presymptomatic individuals and but without any familial relationship):

  • At least 18 years of age
  • Capacity to consent
  • Signature of the informed consent
  • Covered by social security
  • Ability to undergo MRI scanning

Non-Inclusion Criteria:

• Under the age of 18 years of age
• Contra-indications to MRI examination (metallic implant, pacemaker, artificial heart valve, brain vascular malformation, aneurysm clips, exposed by metallic fragments, artificial implants, peripheral or neuronal stimulator, insulin pump, intravenous catheter, epilepsy, person with an history of seizure, metallic contraceptive device, permanent eyelid make up, claustrophobia,…)
• Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
• History of severe head injury
• History of neurological disorder or presence of neurological disorder
• Participation in a drug trial or exclusion period of another study
• Pregnancy or breastfeeding
• Inability to understand information about the protocol
• Person deprived of their liberty by judicial or administrative decision
• Person under legal protection (legal guardianship, tutelage or maintenance of justice)
• Person without any protection and unable to consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Premanifest HTT mutation carriers	Other: Brain imaging; Volume, DWS and DTI; Other: Neurological assessments; UHDRS; Behavioral: Psychological assessments; STAI (Spielberger state and Trait Anxiety Inventory) A and B, BDI-II (Beck Depression Inventory), MINI (Mini-International Neuropsychiatric Interview) and MINI-SEA (mini Social cognitive and Emotional Assessment); Behavioral: Behavioural assessments; Computerized game
OTHER: non HTT mutation carriers	Other: Brain imaging; Volume, DWS and DTI; Other: Neurological assessments; UHDRS; Behavioral: Psychological assessments; STAI (Spielberger state and Trait Anxiety Inventory) A and B, BDI-II (Beck Depression Inventory), MINI (Mini-International Neuropsychiatric Interview) and MINI-SEA (mini Social cognitive and Emotional Assessment); Behavioral: Behavioural assessments; Computerized game

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Detection by Diffusion-weighted spectroscopy of abnormal white matter changes prior to the onset of Huntington disease comparing HTT mutation carriers and non HTT mutation carriers over one year	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
Detection by Diffusion-weighted spectroscopy of abnormal white matter changes over one year as an intersubject evolution	one year
Detection by Diffusion Tensor Imaging of abnormal white matter changes prior to the onset of Huntington disease comparing HTT mutation carriers and non HTT mutation carriers over one year.	one year
Detection by Diffusion Tensor Imaging white matter changes over one year as an intersubject evolution.	one year
Detection of abnormal scores from psychological tests to assess possible early non motor changes and their intersubject evolution over one year.	one year
Detection of choice rates and time differences in the behavioral task comparing HTT mutation carriers and non HTT mutation carriers over one year.	one year
Detection of time differences in the behavioral task comparing HTT mutation carriers and non HTT mutation carriers over one year.	one year

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: University College, London
• Investigators: Principal Investigator: Alexandra DURR, PU-PH, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 11, 2017
• Primary Completion (ACTUAL): December 30, 2019
• Study Completion (ACTUAL): December 30, 2019

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (ACTUAL): June 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 18, 2020
• Last Update Submitted That Met QC Criteria: February 17, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease; Leukoaraiosis
• Other Study ID Numbers: C16-115; 2017-A00589-44 (REGISTRY: RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No