A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy

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 take 2,000 international units (IU) of vitamin D3 daily for a 6 month
period, followed by an increase to 4,000 IU daily for at least 6 months thereafter. The
vitamin D supplements will be provided by the study. In keeping with the current standard of
care for ALD boys aged 3-12 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.

Criteria for enrollment to screening:

1. Molecular confirmation of X-linked ALD (VLCFA elevation & ABCD1 mutation) known in
patient or immediate family member)

2. Male

3. Age 1.5yrs (i.e. 18mos) - 25yrs at screening

Criteria for assignment to drug:

1. Plasma 25-hydroxy vitamin D level ≤ 60ng/ml in past 30 days

2. MRI brain in past 6 months that is negative for evidence of active cerebral
demyelination

Exclusion Criteria:

- history of liver or kidney disease

- history of nephrolithiasis

- history of hyperthyroidism

- history of ulcerative colitis, Crohn's disease, celiac disease

- taking medication interfering with gastrointestinal absorption

- contraindication or inability to complete MRI every 6 months