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

NCT ID: NCT04012411

Last Updated: 2026-02-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

135 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-03

Study Completion Date

2027-09-30

Brief Summary

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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.

Detailed Description

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* Design: Multicentre prospective case-control study. Centres: University Hospital of Montpellier, France; University Hospital of Bordeaux, France; University Hospital of Nimes, France; University Hospital of Poitiers, France.
* Main objective: To evaluate BDNF in cerebrospinal fluid as a potential marker of the BDNF-TrkB signaling pathway in vivo in HD patients at a symptomatic stage.
* Secondary objectives: i) Evaluate plasma BDNF in subjects with HD; ii) Study the correlation between BDNF in CSF and BDNF in plasma; iii) Study the correlation between markers of the BDNF pathway and clinical severity, multimodal brain MRI parameters, and relevant markers of evolution of HD; iv) Confirm the increase of Tau and NFL (Neurofilament Light Chain) markers in plasma and in CSF, as markers of neuronal degeneration, in subjects with HD ; v) Test the TrkB assay in the CSF of patients with HD
* Inclusion Criteria. General inclusion criteria: age ≥ 18 years old; national health insurance cover. Patient inclusion criteria: genetically confirmed Huntington's disease diagnosis (≥ 35 CAG repeat in HTT gene exon 1); written informed consent; patient agreement for LP, if requested. Control inclusion criteria: previous LP for medical reason; agreement for inclusion in a biobank for research purposes.
* Exclusion Criteria. General exclusion criteria: subject protected by law, under curatorship or guardianship. Patients exclusion criteria: too severe HD, according to the clinician's judgment, possibly making difficult to perform cognitive evaluation or MRI; contraindications to brain MRI; contraindications to LP; inability to give informed consent. Control exclusion criteria: presence of a neurodegenerative of inflammatory central nervous system disease.
* Inclusion period: 48 months
* Duration of participation for each patient: 123 days maximum
* Total research duration: 64 months
* Plan of the study. Patients group: in 90 patients with HD, the investigators will perform: a collection of the main anamnestic and clinical data; a blood test for the determination of plasmatic BDNF, Tau and NFL and the genotyping of the Val66Met polymorphism of the BDNF gene; multimodal brain MRI with volumetry, diffusion tensor, functional MRI of rest; a measurement of the severity of Huntington's disease and Total Functional Capacity scales; neuropsychological tests (SDMT, STROOP test, Trail Making Test (TMT) A and B, digit span). In a subgroup of 45 patients, the investigators will also perform a lumbar puncture for the determination of BDNF, Tau, NFL and TrkB in CSF. Control Group: 45 controls will be selected from the samples present in the existing Biobank with CSF and plasma samples available in Montpellier, France. MRI data will be centralized and processed by the Imaging Institute I2FH Montpellier University Hospital.

Conditions

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Huntington Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Patient with LP

Huntington's disease patients who agreed to have LP

Group Type ACTIVE_COMPARATOR

Brain MRI

Intervention Type PROCEDURE

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

Lumbar Punction

Intervention Type PROCEDURE

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

Blood sample

Intervention Type GENETIC

Analysis of BDNF, Tau, NFL, and Val66Met polymorphism

Cognitive evaluation

Intervention Type OTHER

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

Patient without LP

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

Group Type ACTIVE_COMPARATOR

Brain MRI

Intervention Type PROCEDURE

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

Blood sample

Intervention Type GENETIC

Analysis of BDNF, Tau, NFL, and Val66Met polymorphism

Cognitive evaluation

Intervention Type OTHER

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

Control Group

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Brain MRI

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

Intervention Type PROCEDURE

Lumbar Punction

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

Intervention Type PROCEDURE

Blood sample

Analysis of BDNF, Tau, NFL, and Val66Met polymorphism

Intervention Type GENETIC

Cognitive evaluation

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

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Montpellier

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University Hospital of Montpellier

Montpellier, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Cecilia MARELLI, MD

Role: CONTACT

+33(0)467336029

Facility Contacts

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Cecilia Marelli, MD

Role: primary

+33(0)467336029

Other Identifiers

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RECHMPL19_0081

Identifier Type: -

Identifier Source: org_study_id

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