Disease Progression in Women With X-linked Adrenoleukodystrophy

Study Overview
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Brief Summary
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Observational, single-site prospective and minimally interventional study in women with X-linked adrenoleukodystrophy (ALD), conducted in France.

Detailed Description
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Patients accepting participation (after signing ICF) will be followed up to at least 2 years or until they started treatment for X-linked adrenoleukodystrophy (ALD) or withdraw consent, whichever occurs first. Follow-up will be extended beyond 2 years if deemed appropriate after an interim report. Tests and questionnaires will be assessed at baseline and yearly. If the study is extended, beyond 2 years, patients will be assessed at 1-year intervals. At baseline visit and follow-up visits, patients will undergo an MRI of the brain and the spinal cord and assessments of body sway, EDSS, ADL, pain VAS and SF-36 questionnaire. Plasma biomarkers will be assessed from samples obtained through routine blood draw and a monthly falls diary will be provided each visit to be completed once a month. This study will not assess any specific medicinal product or intervention, and the study will not interfere with that prescribed in clinical practice.

Official Title
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An Observational Study to Assess Disease Progression in Women With X-linked Adrenoleukodystrophy

Conditions
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X-linked Adrenoleukodystrophy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18 years old or older. Diagnosis of X-linked ALD based on genetic testing, altered VLCFA levels, or family history. Willing to undergo annual follow-up visits, including brain and spinal cord MRI scans. Provision of written informed consent. Affiliation or beneficiary of a French social security system or of such a regime. Exclusion Criteria: Any condition that in the opinion of the investigator are likely to adversely affect the study participation, interfere with study compliance, or confound the study results. Under treatment or previous treatment with leriglitazone. Pregnant or lactating women. Subjects benefiting from laws aimed at protecting vulnerable adults: subjects being deprived of liberty by judicial or administrative decision, subjects under guardianship. Participation in an interventional clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spinal cord magnetization transfer ratio (MTR) | To assess the disease evolution on spinal cord MRI | Change from baseline up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spinal cord morphometry. Cross sectional area (CSA) to cover the C1 to C7 vertebral levels. | To assess the disease evolution on spinal cord MRI | Change from baseline up to 2 years | 
| Spinal cord diffusion image analysis parameters: Fractional Anisotropy (FA), Radial Diffusivity (RD), Axial Diffusivity (AD), Mean Diffusivity (MD) at the cervical levels C1-C5. | To assess the disease evolution on spinal cord MRI | Change from baseline up to 2 years | 
| Brain diffusion image analysis parameters: Fixel-Based analysis (FBA) (Fiber Density (FD), Fiber cross-section (FC) and combination of FD and FC), Diffusion tensor imaging (DTI) (FA, RD, AD, MD, Markers of severity and markers of evolution). | To assess the disease evolution on brain MRI | Change from baseline up to 2 years | 
| Body sway amplitude (considering antero-posterior and medio-lateral sway with eyes closed, feet apart; eyes open, feet apart; eyes closed, feet together; eyes open, feet together) | To assess clinical evolution of myelopathy | Change from baseline up to 2 years | 
| Expanded Disability Status Scale (EDSS) | To assess the impact on Quality of Life | Change from baseline up to 2 years | 
| Activities of Daily Living (ADL) | To assess the impact on Quality of Life | Change from baseline up to 2 years | 
| Pain Visual Analogue Scale (Pain VAS) | To assess the impact on Quality of Life | Change from baseline up to 2 years | 
| Monthly falls | To assess the impact on Quality of Life | Change from baseline up to 2 years | 
| Short Form Health Survey (SF-36) | To assess the impact on Quality of Life | Change from baseline up to 2 years | 
| Plasma biomarkers (NFL, MMP-9, IL-18, MIP-1beta and IL-1Ra) | To assess the evolution of plasma biomarkers | Change from baseline up to 2 years |