Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy and Metachromatic Leukodystrophy

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Brief Title

Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy and Metachromatic Leukodystrophy

Official Title

MATRIX - "Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy and Metachromatic Leukodystrophy"

Brief Summary

      This study is a national, non-randomized, open-label, multi-site with minimal risk study in
      adult with adrenomyeloneuropathy (AMN) and childhood subjects with cerebral ALD (cALD) or
      late-infantile metachromatic leukodystrophy (LI-MLD) (≤17 years). 28 subjects will be
      enrolled with one blood sample collection during one of their medical follow-up visit.

      This trial will evaluate the role of innate immunity to influence disease progression in
      X-ALD and MLD, and if the mutations related to these leukodystrophies result in a specific
      immune response leading to the pathogenesis.
    

Detailed Description

      X-linked Adrenoleukodystrophy (X-ALD) and Metachromatic Leukodystrophy (MLD) are among the
      most frequent inherited leukodystrophies in childhood and also occur in adults. Both diseases
      are characterized by phenotypic variability and poor genotype-phenotype correlation. In
      childhood forms of LI-MLD and childhood cerebral ALD (C-CALD) a devastating cerebral
      demyelination and neuronal degeneration lead to a rapid neurologic degradation and premature
      death. Patients with the adult form of X-ALD (AMN, 60% of males) display a progressive
      spastic paraplegia without brain involvement. However, 20% of AMN patients will also develop
      cerebral ALD.

      The pathophysiology of X-ALD and MLD is still poorly understood but several arguments argue
      for the contribution of the immune response and neuroinflammation in these leukodystrophies.
      In X-ALD, activation of microglia (macrophages of the CNS) plays an essential role in the
      acute demyelination phase, where a severe inflammatory process occurs. Even if MLD is not
      considered as a neuroinflammatory disease per se, microglia activation and increased
      inflammatory cytokines are observed in the brain of MLD patients and mice. Even if the most
      commonly accepted hypothesis is that neuroinflammation is caused by secondary activation of
      microglia following phagocytosis of myelin debris full of undegraded material, a primitive
      role of macrophages (MAC) dysfunction has emerged in recent years.

      MATRIX proposes to explore how disease-related mutations affect key components of MAC
      activation responses and how it reflects on their functionality.
    


Study Type

Observational


Primary Outcome

Macrophages functionality - distribution of monocytes

Secondary Outcome

 Macrophages metabolic profiling

Condition

Adrenoleukodystrophy

Intervention

Blood sample collection

Study Arms / Comparison Groups

 affected subjects
Description:  adult patients with adrenomyeloneuropathy/adrenoleukodystrophy
children with adrenoleukodystrophy
children with metachromatic leukodystrophy

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Diagnostic Test

Estimated Enrollment

28

Start Date

August 30, 2021

Completion Date

December 2023

Primary Completion Date

June 2023

Eligibility Criteria

        Inclusion Criteria:

          -  Boys aged between 3 and 18 years (inclusive) diagnosed with C-CALD (elevated levels of
             VLCFA and leukodystrophy at brain MRI)

          -  Boys or girls aged between 15 months and 12 years (inclusive) diagnosed with LI-MLD
             (onset <30 months, low ARSA activity and accumulation of sulfatides in urine)

          -  Adult males diagnosed with AMN (elevated VLCFA and clinical symptoms of AMN without
             leukodystrophy at brain MRI)

          -  Children (15 months-18 years) without significant neurologic disease

          -  Informed consent obtained:

          -  from the parents or guardian for children patients and children controls;

          -  from subject himself for adult patients.

        Exclusion Criteria:

          -  Participation to a therapeutic clinical trial

          -  Treatment likely to modify the immune system

          -  Unable to have a blood collection (i.e. low hemoglobin level at the investigator's
             judgment)

          -  Any other reason, to the discretion of the investigator

          -  Children or adults without health insurance or social security
      

Gender

All

Ages

15 Months - 60 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Fanny MOCHEL, MCU-PH, 01 57 27 44 82, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT04925349

Organization ID

APHP190197


Responsible Party

Sponsor

Study Sponsor

Assistance Publique - Hôpitaux de Paris


Study Sponsor

Fanny MOCHEL, MCU-PH, Principal Investigator, Institut du Cerveau et de la Moëlle épinière


Verification Date

September 2021