Study of Biomarkers That Predict the Evolution of Huntington's Disease (BIOHD)

Huntington's disease (HD) is a rare, autosomal dominant, progressive neurodegenerative disorder typically becoming noticeable in middle age. It is clinically characterized by progressive involuntary movements (bradykinesia and hyperkinesia), neuropsychiatric disturbances (depression, irritability), and cognitive impairments progressing to dementia.

The striatum (caudate and putamen) is the primary area of neuronal degeneration in HD. Today, there is no validated curative treatment. HD affects approximately 6 000 patients in France and more than 30 000 individuals are considered at risk for this disease.

While the disease gene is discovered and we are capable to do a predictive genetic diagnosis for asymptomatic patients, there is no clinical or biological way to predict the age of onset or the progressive profile of patients.

One of the fundamental characteristics of this disease is its extreme variability from one patient to other both in terms of their evolution and their onset of action. Thus, this inter-individual variability severely limits the genetic counselling and complicating the neurological assessment.

Increasingly, it has been assumed that modifier genes may be the source of this inter-individual variability and that their identification could help the understanding and prediction of disease progression.

Given that the mutant protein is ubiquitous, the molecular dysfunction of neurons could be found in peripheral cells from the bloodstream and will be more accessible to investigation.

Study Overview

• Status: Unknown
• Conditions: Huntington Disease
• Intervention / Treatment: Other: Huntington patient evaluation; Other: Healthy subject evaluation

Detailed Description

In this context, we propose to focus our research not only on biological and genetic markers but also on neuroimaging and neuropsychological markers using paradigms of time reactions or measurement of evoked potentials. We hope to identify sensitive markers of the degenerative process of Huntington's disease even when patients carrying the gene may or may not have reported the disease.

The project is centered on 2 axes:

1. identification of the genetic polymorphism which may explain the phenotypic variability seeing in Huntington's disease
2. identification of biological, genetic and imaging biomarkers that could be used as predictors of clinical progression of Huntington's disease This research is based on the existence of a well followed and well characterized cohort of patients through the Francophone Huntington Network ("RESEAU HUNTINGTON de LANGUE FRANCAISE", RHLF). Therefore, this will help to combine the clinical and biological expertise of RHLF.

• Study Type: Observational
• Enrollment (Anticipated): 1800

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94010
    • Recruiting
    • Hopital Henri Mondor
    • Contact: Bachoud-Lévi Anne-Catherine, PH; Phone Number: +33 (0)1 49 81 23 01; Email: bachoud@gmail.com
    • Principal Investigator: Bachoud-Lévi Anne-Catherine, PH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients suffering from Huntington disease (carrying the gene) versus healthy controls

Description

Inclusion Criteria (patient):

• Voluntary patients symptomatic or asymptomatic
• Patient with a number of CAG ≥36)
• Patient who know his genetic status
• Age greater than 18 years or equal to 18 years
• Patient who provided written informed consent

Exclusion Criteria (patient):

- Deterioration of the protocol preventing the understanding of the protocol

Inclusion Criteria (control):

• Voluntary controls with no family history of huntington's disease
• Control with a number of CAG <36
• Age greater than 18 years or equal to 18 years
• Control who provided written informed consent

Exclusion Criteria (control):

- Deterioration of the protocol preventing the understanding of the protocol

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patient; Voluntary Huntington patients symptomatic or asymptomatic, with a number of nucleotide expansion(CAG) ≥36 and who know their genetic status	Other: Huntington patient evaluation; Neurological, neuropsychological, neuroimaging evaluation and biological sample
Healthy subject; Voluntary controls with no family history of huntington's disease	Other: Healthy subject evaluation; Neurological, neuropsychological, neuroimaging evaluation and biological sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unified Huntington Disease Rating Scale (UHDRS)	The period of follow-up will achieve at the end of 2020	up to 9 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mattis Dementia Rating Scale	The period of follow-up will achieve at the end of 2020	up to 9 years
Trail Making test A et B	The period of follow-up will achieve at the end of 2020	up to 9 years
Hopkins Verbal Learning Test	The period of follow-up will achieve at the end of 2020	up to 9 years
Categorical Fluency	The period of follow-up will achieve at the end of 2020	up to 9 years
Language tests	The period of follow-up will achieve at the end of 2020	up to 9 years
Social cognition tests	The period of follow-up will achieve at the end of 2020	up to 9 years
Comportment scale	The period of follow-up will achieve at the end of 2020	up to 9 years
Neuroimaging	The period of follow-up will achieve at the end of 2020	up to 9 years
Neuropsychological evaluation	The period of follow-up will achieve at the end of 2020	up to 9 years
Electrophysiological tests	The period of follow-up will achieve at the end of 2020	up to 9 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Bachoud-Lévi Anne-Catherine, PH, Assistance Publique - Hopitaux de Paris

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: August 5, 2011
• First Posted (Estimate): August 9, 2011

Study Record Updates

• Last Update Posted (Estimate): October 9, 2014
• Last Update Submitted That Met QC Criteria: October 8, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Biomarkers; Neuropsychology; Genetic polymorphism; Neuroimaging markers
• Additional Relevant MeSH Terms: Mental Disorders; 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
• Other Study ID Numbers: P090302