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Report for Clinical Trial NCT04012411

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Study of Brain Derived Neurotrophic Factor (BDNF) Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntington's Disease

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.

NCT04012411 Huntington Disease
MeSH:Huntington Disease

4 Interventions

Name: Brain MRI

Description: Multimodal brain MRI: volumetry, diffusion tensor, functional rest MRI
Type: Procedure
Group Labels: 2

Patient with LP Patient without LP

Name: Lumbar Punction

Description: Analysis of BDNF, Tau, NFL and TrkB in cerebrospinal fluid
Type: Procedure
Group Labels: 1

Patient with LP

Name: Blood sample

Description: Analysis of BDNF, Tau, NFL, and Val66Met polymorphism
Type: Genetic
Group Labels: 2

Patient with LP Patient without LP

Name: Cognitive evaluation

Description: Symbol Digit Modality Test (SDMT), Stroop test, Trail Making Test, Empan
Type: Other
Group Labels: 2

Patient with LP Patient without LP

Primary Outcomes

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

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

Time: Inclusion

Secondary Outcomes

Measure: plasmatic BDNF in HD subjects vs controls

Time: Inclusion

Measure: Correlation between BDNF in CSF and BDNF in plasma

Time: Inclusion

Description: Correlation between BDNF in CSF or plasma and: disease severity, assessed through the Huntington Disease Rating Scale (UHDRS), the disease burden formula [(n.CAG-35.5) x age], the Total Functional Capacity functional scale (TFC), and cognitive scales (Symbol Digit Modalities Test, STROOP test, Trail Making test A and B, direct and indirect digit span); - MRI brain imaging: cerebral and striatal atrophy by morphological imaging, functional resting state MRI, and anatomical connectivity by diffusion tensor imaging

Measure: Correlation between BDNF and disease parameters

Time: Inclusion

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

Time: Inclusion

Measure: TrkBcsf level in subjects with HD vs control subjects

Time: Inclusion

Purpose: Basic Science

Allocation: Non-Randomized

Parallel Assignment

There is one SNP


1 V66M

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 UHDRS and Total Functional Capacity scales; neuropsychological tests (SDMT, STROOP test, Trail Making Test (TMT) A and B, digit span). --- Val66Met ---

HPO Nodes