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Trial record 2 of 193 for:    "huntington disease"

Study of BDNF Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntington's Disease (LCR-MH)

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ClinicalTrials.gov Identifier: NCT04012411
Recruitment Status : Not yet recruiting
First Posted : July 9, 2019
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Montpellier

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.


Condition or disease Intervention/treatment Phase
Huntington Disease Procedure: Brain MRI Procedure: Lumbar Punction Genetic: Blood sample Other: Cognitive evaluation Not Applicable

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 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: 23 months
  • Duration of participation for each patient: 123 days maximum
  • Total research duration: 24 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 UHDRS 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Study of Brain Derived Neurotrophic Factor (BDNF) Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntington's Disease
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Patient with LP
Huntington's disease patients who agreed to have LP
Procedure: Brain MRI
Multimodal brain MRI: volumetry, diffusion tensor, functional rest MRI

Procedure: Lumbar Punction
Analysis of BDNF, Tau, NFL and TrkB in cerebrospinal fluid

Genetic: Blood sample
Analysis of BDNF, Tau, NFL, and Val66Met polymorphism

Other: Cognitive evaluation
Symbol Digit Modality Test (SDMT), Stroop test, Trail Making Test, Empan

Active Comparator: Patient without LP
Huntington's disease patient with contraindication to LP or refusal to have LP
Procedure: Brain MRI
Multimodal brain MRI: volumetry, diffusion tensor, functional rest MRI

Genetic: Blood sample
Analysis of BDNF, Tau, NFL, and Val66Met polymorphism

Other: Cognitive evaluation
Symbol Digit Modality Test (SDMT), Stroop test, Trail Making Test, Empan

No Intervention: Control Group
Retrospective study with biologic samples of patients without Huntington's disease



Primary Outcome Measures :
  1. BDNF(csf) in HD subjects compared to age-matched control subjects (+/- 5 years) [ Time Frame: Inclusion ]
    centralized ELISA assay with Simoa - Quanterix kit technology at the Laboratory of Clinical Proteomic Biochemistry of Montpellier, France.


Secondary Outcome Measures :
  1. plasmatic BDNF in HD subjects vs controls [ Time Frame: Inclusion ]
  2. Correlation between BDNF in CSF and BDNF in plasma [ Time Frame: Inclusion ]
  3. Correlation between BDNF and disease parameters [ Time Frame: Inclusion ]
    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

  4. Total Tau and NFL levels in plasma and CSF in HD subjects vs control subjects [ Time Frame: Inclusion ]
  5. TrkBcsf level in subjects with HD vs control subjects [ Time Frame: Inclusion ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • General inclusion criteria:

    • age ≥ 18 years-old
    • national health insurance cover
  • Patients inclusion criteria:

    • 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
  • Control inclusion criteria:

    • 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:

  • General exclusion criteria:

    • protected by law
  • Patients exclusion criteria:

    • 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
  • Control exclusion criteria:

    • neurodegenerative of inflammatory central nervous system pathology

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04012411


Locations
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France
University Hospital of Montpellier Not yet recruiting
Montpellier, France
Contact: Cecilia Marelli       c-marelli@chu-montpellier.fr   
Contact: Diana Ban       d-ban@chu-montpellier.fr   
Sponsors and Collaborators
University Hospital, Montpellier

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Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT04012411     History of Changes
Other Study ID Numbers: 19_0081
First Posted: July 9, 2019    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Montpellier:
Huntington Disease
CSF
Biomarkers
BDNF
P42
Additional relevant MeSH terms:
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Huntington Disease
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
Cognition Disorders
Neurocognitive Disorders
Mental Disorders