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

• ClinicalTrials.gov Identifier: NCT01412125
• Recruitment Status: Unknown
• First Posted: August 9, 2011
• Last Update Posted: October 9, 2014
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Huntington Disease	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 Design

• Study Type: Observational
• Estimated Enrollment: 1800 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Study of Biomarkers That Predict the Evolution of Huntington's Disease
• Study Start Date: September 2003
• Estimated Primary Completion Date: January 2021
• Estimated Study Completion Date: January 2021

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Unified Huntington Disease Rating Scale (UHDRS) [ Time Frame: up to 9 years ]
   The period of follow-up will achieve at the end of 2020

Secondary Outcome Measures :

1. Mattis Dementia Rating Scale [ Time Frame: up to 9 years ]
   The period of follow-up will achieve at the end of 2020
2. Trail Making test A et B [ Time Frame: up to 9 years ]
   The period of follow-up will achieve at the end of 2020
3. Hopkins Verbal Learning Test [ Time Frame: up to 9 years ]
   The period of follow-up will achieve at the end of 2020
4. Categorical Fluency [ Time Frame: up to 9 years ]
   The period of follow-up will achieve at the end of 2020
5. Language tests [ Time Frame: up to 9 years ]
   The period of follow-up will achieve at the end of 2020
6. Social cognition tests [ Time Frame: up to 9 years ]
   The period of follow-up will achieve at the end of 2020
7. Comportment scale [ Time Frame: up to 9 years ]
   The period of follow-up will achieve at the end of 2020
8. Neuroimaging [ Time Frame: up to 9 years ]
   The period of follow-up will achieve at the end of 2020
9. Neuropsychological evaluation [ Time Frame: up to 9 years ]
   The period of follow-up will achieve at the end of 2020
10. Electrophysiological tests [ Time Frame: up to 9 years ]
    The period of follow-up will achieve at the end of 2020

Biospecimen Retention:   Samples With DNA

• Blood (for DNA analysis) and plasma sample at inclusion visit
• Plasma sample every year

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

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

Criteria

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

Contacts and Locations

Contacts

Contact: Bachoud-Levi Anne-Catherine, PH; (0)1 49 81 23 01 ext +33; bachoud@gmail.com

Locations

France

Hôpital Henri Mondor; Recruiting

Creteil, France, 94010

Contact: Bachoud-Lévi Anne-Catherine, PH (0)1 49 81 23 01 ext +33 bachoud@gmail.com

Principal Investigator: Bachoud-Lévi Anne-Catherine, PH

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

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

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT01412125
• Other Study ID Numbers: P090302
• First Posted: August 9, 2011
• Last Update Posted: October 9, 2014
• Last Verified: October 2014

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Biomarkers; Genetic polymorphism; Neuroimaging markers; Neuropsychology

Additional relevant MeSH terms:

Huntington Disease; 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; Cognition Disorders; Neurocognitive Disorders; Mental Disorders