Early Diagnosis Of Childhood Cerebral ALD

Study Overview
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Brief Summary
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The goal of this single institution study is to evaluate boys with adrenoleukodystrophy (ALD) diagnosed early in life, and to prospectively monitor them to determine parameters that will facilitate earlier detection of the childhood cerebral form of the disease. These at-risk subjects will be assessed yearly through travel to the University of Minnesota, where plasma and cerebral spinal fluid (CSF) biomarker studies, MRI based imaging and neuropsychological assessments will be performed at the University of Minnesota Masonic Children's Hospital and Clinics. The MRI and lumbar puncture to obtain CSF will be obtained under sedation. In addition, at intervening 6 months intervals information will be obtained remotely, including surveys and MRI's in their home location. Also at that time blood samples will be obtained locally and shipped to the University of Minnesota for study. There is no therapeutic intent in this study.

Official Title
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Early Diagnosis Of Childhood Cerebral Adrenoleukodystrophy

Conditions
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Adrenoleukodystrophy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Boys with confirmed adrenoleukodystrophy, as determined by very long chain fatty acid (VLCFA) analysis and/or genotyping. Genotyping is not necessary for diagnosis. Between 1 and 5 years of age, inclusive at the time of consent. Able to undergo a sedation English as primary language of the household, to maximize consistency of the neuropsychological/developmental testing. Voluntary written parental/guardian consent Exclusion Criteria: Evidence of cerebral disease at time of enrollment - patients over 3 years of age must have an MRI within 4 months of signing consent to confirm that there is no evidence of cerebral disease Inability or unwillingness to travel to the University of Minnesota once a year for the duration of the study Evidence of cerebral disease by standard T2/FLAIR MRI. If a subject develops cerebral ALD during the study, they will come off study, as it is anticipated that they would be considered for transplantation.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 5 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- | --- |
| ALD Early Evaluation | To evaluate boys with adrenoleukodystrophy (ALD) diagnosed early in life, and to prospectively determine factors that have a high correlation with the emergence of cerebral ALD. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Emergence of cerebral disease through imaging | The ability to discern the emergence of cerebral disease through imaging prior to the onset of classic T2 imaging. This will include diffusion tensor imaging (DTI), T1 and T2 rho, RAFF and spectroscopy, in addition to the standard MRI evaluations including gadolinium enhancement. | 5 years | 
| Biomarker Study: Inflammation Markers | Markers of inflammation (chitotriosidase, lipidomics including arachidonic acid metabolites and inflammatory cytokines). | 5 years | 
| Biomarker Study: Oxidative Stress | Determinations of oxidative stress (including but not limited to total and reduced/oxidized glutathione and 4-hydroxynonenal, or 4-HNE). | 5 years | 
| Biomarker Study: Immunologic Activation |  | 5 years | 
| Neuropsychology testing | Extensive neuropsychology testing, including assessments of verbal comprehension, perceptual reasoning, working memory and processing speed. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALD, Newborn Screening