About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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)
Disqualifiers
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
Trial 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
Trial design
Case-control
Prospective
Treatments tested in this trial
Blood sample collection
Diagnostic testblood sample collection
Treatment groups
Trial outcomes
Primary outcomes
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-)
Macrophages functionality - myelin phagocytosis capacity
percentage of myelin high, myelin low and myelin negative cells using flow cytometry
Macrophages functionality - HLA levels
maximum fluorescence intensity for HLA markers using flow cytometry
Secondary outcomes
Macrophages metabolic profiling
Macrophages metabolic profiling (\>2000 metabolites) using liquid chromatography coupled to high resolution mass spectrometry
Macrophages transcriptomic profiling
Macrophages transcriptomic profiling (\>1200 coding and non coding genes) : RNA sequencing using NextSeq 500 Illumina (60 million single-end, 150 base reads ) and analysis (using FastQC, Picard-Tools, Samtools and rseqc softwares
Sponsors and contacts
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Assistance Publique - Hôpitaux de Paris
Lead sponsor
URC-CIC Paris Descartes Necker Cochin
Collaborator