A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy
Condition: X-linked Adrenoleukodystrophy
MeSH terms: Adrenoleukodystrophy
Study type: Interventional
Phase: Phase 1

Summary: 
      In this pilot study, the investigators will assess the safety of two high-dose regimens of
      oral vitamin D supplementation and measure the effects of vitamin D supplementation on
      markers of oxidative stress and inflammation in the blood and brain of study participants
      before, during, and after taking vitamin D supplements.

      The goal of the study is to establish research measures (i.e. biomarkers) and an optimal dose
      for vitamin D supplementation in boys with the X-linked adrenoleukodystrophy (ALD) genotype.
    

Detailed description: 
      Prior research suggests that higher vitamin D levels in the blood are associated with reduced
      brain inflammation among individuals with multiple sclerosis, a disease that is similar to
      the cerebral demyelinating form of ALD. However, serious side effects (e.g. hypercalcemia,
      kidney stones) can occur if vitamin D levels get too high.

      The current study is designed to establish a safe dose of vitamin D for boys with ALD.
      Although the doses chosen for this study are expected to be safe, the investigators will
      monitor participants for early signs of vitamin D-related toxicity. The investigators will
      also examine whether or not vitamin D supplementation affects markers of oxidative stress and
      inflammation in the blood and brains of ALD boys.

      The study requires participants to agree to at least one year of participation. Participants
      will be asked to take a vitamin D supplement every day, submit blood for analysis every 3
      months in the first year, and visit their study center (Stanford University or the Kennedy
      Krieger Institute) every 6 months throughout the period of study.

      Participants will be assigned a vitamin D dose based on bodyweight at entry. Starting doses
      will include 1,000 or 2,000 international units (IU) of vitamin D3 daily for a 6 month
      period, followed by a conditional increase to 2,000, 3,000, or 4,000 IU daily thereafter if
      vitamin D levels have not achieved a target threshold. The vitamin D supplements will be
      provided by the study. In keeping with the current standard of care for ALD boys aged 18mos -
      25 years, participants will need to visit the study site every six months in order to
      complete a clinic visit and MRI of the brain with gadolinium. As part of this study, however,
      participants' will need to submit blood work every 3 months during the first year in order
      for the study investigators to ensure that the participants' calcium and vitamin D levels are
      in a safe range and to study the effects of vitamin D on markers in the blood. The MRI
      protocol during the first year will also include one additional sequence (magnetic resonance
      spectroscopy) in order to measure brain metabolites.

      The data generated from this study are intended, in part, to help design a future,
      large-scale clinical trial to determine whether vitamin D supplementation is capable of
      reducing the risk of developing the cerebral demyelinating form of ALD.
    

Intervention name(s): vitamin D3
Intervention type(s): Dietary Supplement
Intervention description(s): Daily oral supplement provided by study investigators
Other intervention name(s): vitamin D
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Intervention model: Single Group Assignment
Intervention model description: single-arm dose escalation
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Leukodystrophy; ABCD1; Demyelination; Inflammation; ALD; Vitamin D; Oxidative Stress; X- linked; Adrenoleukodystrophy