Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia

NCT04925349 | Recruiting

• 2 other identifiers: APHP190197IDRCB
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a national, non-randomized, open-label, multi-site with minimal risk study in adult with adrenomyeloneuropathy (AMN), childhood and adult subjects with cerebral ALD (cALD), juvenile/adult metachromatic leukodystrophy (MLD) and adults with leukoencephalopathy and axonal spheroids and pigmented glia (ALSP). 49 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, MLD and ALSP, and if the mutations related to these leukodystrophies result in a specific immune response leading to the pathogenesis.

Conditions

Adrenoleukodystrophy; Adrenomyeloneuropathy; Metachromatic Leukodystrophy; Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia

Keywords

Leukodystrophy; Central Nervous System Diseases; Nervous System Diseases; Immune system; Neuroinflammation

Outcome Measures

Primary Outcomes (3)

• Macrophages functionality - distribution of monocytes

  distribution of monocytes in the CD14-/+/++ and CD16-/+ classification using flow cytometry (% of CD14++/16-; CD14++/16+; CD14+/16+; CD14-/16-)

  2 years after blood collection

• Macrophages functionality - myelin phagocytosis capacity

  percentage of myelin high, myelin low and myelin negative cells using flow cytometry

  2 years after blood collection

• Macrophages functionality - HLA levels

  maximum fluorescence intensity for HLA markers using flow cytometry

  2 years after blood collection

Secondary Outcomes (2)

• Macrophages metabolic profiling

  2 years after blood collection

• Macrophages transcriptomic profiling

  2 years after blood collection

Study Arms (2)

affected subjects

* adult patients with adrenomyeloneuropathy/adrenoleukodystrophy * children with adrenoleukodystrophy * children with metachromatic leukodystrophy

Diagnostic Test: Blood sample collection

control subjects

* healthy children * heatthy adults

Diagnostic Test: Blood sample collection

Interventions

Blood sample collection DIAGNOSTIC_TEST

blood sample collection

affected subjects; control subjects

Eligibility Criteria

• Age: 15 Months - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Pediatric and adult populations. Both affected (C-CALD, AMN, A-CALD, MLD, ALSP), presymptomatic children carrying ABCD1 mutations (PRE-ALD), presymptomatic patient adults carrying CSF1R mutations (PRE-ALSP) and age-matched control subjects will be enrolled (N=10/group). Minor subjects (C-CALD, MLD, PRE-ALD and controls) will be included, based on childhood onset of C-CALD and MLD

You may qualify if:

• 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 18 years (inclusive) diagnosed with MLD (low ARSA activity and accumulation of sulfatides in urine)
• Presymptomatic boys carrying ABCD1 mutations aged between 3 and 18 years (inclusive) (PRE-ALD)
• Adult males or females aged between 18 and 60 diagnosed with MLD (low ARSA activity and accumulation of sulfatides in urine)
• Males aged between 18 and 60 years diagnosed with AMN (elevated VLCFA and clinical symptoms of AMN without leukodystrophy at brain MRI)
• Males aged between 18 and 60 years diagnosed with CALD (elevated VLCFA with leukodystrophy at brain MRI)
• Adult males or females aged between 18 and 60 years diagnosed with ALSP (CSF1R mutation and leukodystrophy at brain MRI)
• Presymptomatic patient adults (males or females) carrying CSF1R mutations (PRE-ALSP)
• Children (15 months-18 years) without neurologic disease (no obvious neurological symptoms, normal neurologic examination)
• Adults aged between 18 and 60 years without neurologic disease (no overt neurological symptoms)
• Informed consent obtained :
• from the parents or guardian for children patients and children controls;
• from subject himself for adult patients and adult controls.

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (2)

AP-HP Hôpital Bicêtre

Le Kremlin-Bicêtre, 94275, France

RECRUITING

AP-HP Hôpital La Pitié Salpêtrière

Paris, 75013, France

RECRUITING

Related Publications (4)

• Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams A, Franklin RJM, Ffrench-Constant C. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 2013 Sep;16(9):1211-1218. doi: 10.1038/nn.3469. Epub 2013 Jul 21.

  PMID: 23872599 BACKGROUND

• Weinhofer I, Zierfuss B, Hametner S, Wagner M, Popitsch N, Machacek C, Bartolini B, Zlabinger G, Ohradanova-Repic A, Stockinger H, Kohler W, Hoftberger R, Regelsberger G, Forss-Petter S, Lassmann H, Berger J. Impaired plasticity of macrophages in X-linked adrenoleukodystrophy. Brain. 2018 Aug 1;141(8):2329-2342. doi: 10.1093/brain/awy127.

  PMID: 29860501 BACKGROUND

• Berger J, Forss-Petter S, Eichler FS. Pathophysiology of X-linked adrenoleukodystrophy. Biochimie. 2014 Mar;98(100):135-42. doi: 10.1016/j.biochi.2013.11.023. Epub 2013 Dec 4.

  PMID: 24316281 BACKGROUND

• Gieselmann V, Krageloh-Mann I. Metachromatic leukodystrophy--an update. Neuropediatrics. 2010 Feb;41(1):1-6. doi: 10.1055/s-0030-1253412. Epub 2010 Jun 22.

  PMID: 20571983 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

blood sample for MAC analyses and blood sample for blood cells count

MeSH Terms

Conditions

Adrenoleukodystrophy; Leukodystrophy, Metachromatic; Hereditary Diffuse Leukoencephalopathy with Spheroids; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Sulfatidosis; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Fanny MOCHEL, MCU-PH

  Institut du Cerveau et de la Moëlle épinière

  PRINCIPAL INVESTIGATOR

• Violetta ZUJOVIC, PhD, CR1

  Institut du Cerveau et de la Moëlle épinière

  STUDY CHAIR

• Caroline SEVIN, PhD

  Kremlin Bicêtre Hôpital

  STUDY DIRECTOR

Central Study Contacts

Fanny MOCHEL

CONTACT

01 57 27 44 82; fanny.mochel@icm-institut.org

Christelle AUGER

CONTACT

christelle.auger@aphp.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: June 14, 2021
• Study Start: August 30, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: September 24, 2025

Record last verified: 2025-09

Locations

FR (2)