Decoding Presymptomatic White Matter Changes in Huntington Disease

NCT03193099 | Completed

• 2 other identifiers: C16-1152017-A00589-44
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Huntington Disease; White Matter Alterations

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

Study Arms (2)

Premanifest HTT mutation carriers

OTHER

Other: Brain imaging; Other: Neurological assessments; Behavioral: Psychological assessments; Behavioral: Behavioural assessments

non HTT mutation carriers

OTHER

Other: Brain imaging; Other: Neurological assessments; Behavioral: Psychological assessments; Behavioral: Behavioural assessments

Interventions

Brain imaging OTHER

Volume, DWS and DTI

Premanifest HTT mutation carriers; non HTT mutation carriers

Neurological assessments OTHER

UHDRS

Premanifest HTT mutation carriers; non HTT mutation carriers

Psychological assessments BEHAVIORAL

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)

Premanifest HTT mutation carriers; non HTT mutation carriers

Behavioural assessments BEHAVIORAL

Computerized game

Premanifest HTT mutation carriers; non HTT mutation carriers

Eligibility Criteria

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

You may qualify if:

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

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• University College, London: collaborator

Study Sites (1)

Brain and Spine Institute

Paris, 750013, France

Location

MeSH Terms

Conditions

Huntington Disease; Leukoaraiosis

Interventions

Neuroimaging

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Investigative Techniques

Study Officials

• Alexandra DURR, PU-PH

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 20, 2017
• Study Start: July 11, 2017
• Primary Completion: December 30, 2019
• Study Completion: December 30, 2019
• Last Updated: February 18, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)