Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04012411 |
| Other study ID # |
19_0081 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 3, 2020 |
| Est. completion date |
February 2026 |
Study information
| Verified date |
May 2024 |
| Source |
University Hospital, Montpellier |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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 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.
