Study of BDNF Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntington's Disease

NCT04012411 | Recruiting

• 1 other identifier: RECHMPL19_0081
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

Huntington disease (HD, 1.3/10 000) is an autosomal dominant disease due to an abnormal expansion of CAG triplets in HTT gene. Several pathophysiological mechanisms have been evoked, including an alteration of the signaling pathway of the Brain Derived Neurotrophic Factor (BDNF), a neurotrophic factor involved in the survival of neurons (striatal and hippocampal) and synaptic plasticity. BDNF is synthesized at the level of cortical neurons and transported, through the axonal transport in which the Htt is involved, to the nerve endings; it's then secreted in response to excitatory synaptic activity, especially at the level of glutamatergic synapses. Besides, at the postsynaptic level it binds with great specificity to TrkB receptors (tropomyosin-related kinase receptors B) with a neuroprotective effect on dendritic and axonal growth and an increase in synaptic plasticity, especially at the level of the striatum and the hippocampus. BDNF is decreased in the brain of animal models, as well as in patients with HD; the alteration of this pathway would occur in the early stages of the disease. In the context of concomitant multiple treatments, the BNDF pathway may be one of the therapeutic targets of HD. Moreover, in HD it remains essential to detect biological markers representative of the different pathogenic pathways that can be tested in vivo in humans to confirm the hypotheses developed at the level of basic research; these biomarkers could subsequently become biomarkers of disease progression and/or biomarkers of therapeutic efficacy of potential targeted treatments. Therefore, this study aims to characterize potential biomarkers of the BNDF pathway in plasma and CSF in subjects with HD and to confirm the importance of this pathogenic mechanism in vivo in humans.

Conditions

Huntington Disease

Keywords

Huntington Disease; CSF; Biomarkers; BDNF; P42

Outcome Measures

Primary Outcomes (1)

• BDNF(csf) in HD subjects compared to age-matched control subjects (+/- 5 years)

  centralized ELISA assay with Simoa - Quanterix kit technology at the Laboratory of Clinical Proteomic Biochemistry of Montpellier, France.

  Inclusion

Secondary Outcomes (5)

• plasmatic BDNF in HD subjects vs controls

  Inclusion

• Correlation between BDNF in CSF and BDNF in plasma

  Inclusion

• Correlation between BDNF and disease parameters

  Inclusion

• Total Tau and NFL levels in plasma and CSF in HD subjects vs control subjects

  Inclusion

• TrkBcsf level in subjects with HD vs control subjects

  Inclusion

Study Arms (3)

Patient with LP

ACTIVE COMPARATOR

Huntington's disease patients who agreed to have LP

Procedure: Brain MRI; Procedure: Lumbar Punction; Genetic: Blood sample; Other: Cognitive evaluation

Patient without LP

ACTIVE COMPARATOR

Huntington's disease patient with contraindication to LP or refusal to have LP

Procedure: Brain MRI; Genetic: Blood sample; Other: Cognitive evaluation

Control Group

NO INTERVENTION

Retrospective study with biologic samples of patients without Huntington's disease

Interventions

Brain MRI PROCEDURE

Multimodal brain MRI: volumetry, diffusion tensor, functional rest MRI

Patient with LP; Patient without LP

Lumbar Punction PROCEDURE

Analysis of BDNF, Tau, NFL and TrkB in cerebrospinal fluid

Patient with LP

Blood sample GENETIC

Analysis of BDNF, Tau, NFL, and Val66Met polymorphism

Patient with LP; Patient without LP

Cognitive evaluation OTHER

Symbol Digit Modality Test (SDMT), Stroop test, Trail Making Test, Empan

Patient with LP; Patient without LP

Eligibility Criteria

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

You may qualify if:

• age ≥ 18 years-old
• national health insurance cover
• genetically confirmed Huntington's disease diagnosis (≥ 35 CAG repeat in HTT gene exon 1)
• written informed consent
• only for patients "with lumbar puncture (LP)": patient agreement for LP
• anterior LP for medical reason with consent for biobank "Neuro" with following samples present in this biobank : 2 mL blood + 0.5 mL plasma + 0.5 mL cerebrospinal fluid
• information and non-opposition for the finality of this biobank
• paired by age with a patient (+/- 5 years difference)

You may not qualify if:

• protected by law
• Huntington's disease stage too Evolved that may interfere with cognitive evaluations or MRI
• contraindications to brain MRI
• only for patients "with LP": contraindications to LP
• incapacity to give informed consent
• neurodegenerative of inflammatory central nervous system pathology

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

University Hospital of Montpellier

Montpellier, France

RECRUITING

MeSH Terms

Conditions

Huntington Disease

Interventions

Blood Specimen Collection

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

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Cecilia MARELLI, MD

CONTACT

+33(0)467336029; c-marelli@chu-montpellier.fr

Study Design

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

Study Record Dates

• First Submitted: July 4, 2019
• First Posted: July 9, 2019
• Study Start: March 3, 2020
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

FR (1)