Ignite Creation Date:
2024-05-06 @ 1:25 PM
Last Modification Date:
2024-10-26 @ 1:13 PM
Study NCT ID:
NCT04012411
Status:
RECRUITING
Last Update Posted:
2024-05-29
First Post:
2019-07-04
Brief Title:
Study of BDNF Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntingtons Disease
Sponsor:
University Hospital Montpellier
Organization:
University Hospital Montpellier
Study Overview
Official Title:
Study of Brain Derived Neurotrophic Factor BDNF Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntingtons Disease
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LCR-MH
Brief Summary:
Huntington disease HD 1310 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 its 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 andor 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
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 its 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 andor 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:
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 Huntingtons 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 clinicians 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 Huntingtons 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
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 Huntingtons 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 clinicians 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 Huntingtons 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None