A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy
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|ClinicalTrials.gov Identifier: NCT02595489|
Recruitment Status : Recruiting
First Posted : November 3, 2015
Last Update Posted : October 13, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|X-linked Adrenoleukodystrophy||Dietary Supplement: vitamin D3||Phase 1 Phase 2|
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 University of Minnesota) 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy|
|Study Start Date :||March 2016|
|Estimated Primary Completion Date :||March 2019|
|Estimated Study Completion Date :||March 2019|
Experimental: Vitamin D3
Single-arm, dose-escalation starting at 2,000 IU of vitamin D3 daily for a 6 month period, followed by a 4,000 IU daily for at least 6 months thereafter. No placebo.
Dietary Supplement: vitamin D3
Daily oral supplement provided by study investigators
- Percent of patients with a plasma 25-OH vitamin D level in the target range (40-80ng/ml) at 12 months [ Time Frame: Plasma 25-OH vitamin D will be measured at 12 months ]The investigators expect 100% of patients will be in the target range at 12 months (i.e. oral dose of 4000 IU daily)
- Percent of patients with a plasma 25-OH vitamin D level in the target range (40-80ng/ml) at 6 months [ Time Frame: Plasma 25-OH vitamin D will be measured at 6 months ]The investigators expect that 80% of patients will be in the target range 6 months (i.e. oral dose of 2000 IU daily)
- Correlation between appearance of gadolinium enhancing brain lesion on MRI and most recent plasma 25-OH vitamin D level [ Time Frame: Brain MRI at baseline, 6, 12, 18, 24, 30, and 36 months study enrollment. Plasma 25-OH vitamin D levels at baseline, 3, 6, 9, 12, 18, 24, 30, 36 months of enrollment. ]For participants developing gadolinium enhancing lesions on MRI, the investigators will compare the most recent preceding 25-OH vitamin D level with the average 25-OH vitamin D level of participants in the study who did not develop gadolinium enhancing lesions. The investigators expect the development of gadolinium enhancing lesion on MRI will correlate with lower vitamin D levels. However, our current study is not sufficiently powered to measure this effect.
- Change in protein carbonyl levels in whole blood at baseline and 12 months. [ Time Frame: Measurements at baseline and 12months ]The investigators expect a decrease in whole blood protein carbonyl levels between baseline and 12 months.
- Correlation between plasma 25-OH vitamin D and intracellular glutathione levels in peripheral monocytes [ Time Frame: Measurements at baseline and 12 months ]The investigators will use flow cytometry to measure intracellular GSH in CD14+ monocytes from participants peripheral blood at baseline and 12 months. The investigators will measure plasma 25-OH vitamin at the same time points. The investigators expect a positive correlation between plasma vitamin D levels and monocyte GSH levels.
- Change in glutathione (GSH) levels in blood [ Time Frame: Measurements will be obtained at baseline, 6months, and 12months ]The investigators expect a positive correlation between plasma 25-OH vitamin levels and GSH levels in whole blood (measured by tandem mass spectroscopy).
- Change in glutathione (GSH) levels in brain [ Time Frame: Measurements will be obtained at baseline, 6months, and 12months ]The investigators will examine the correlation between 25-OH vitamin D levels in plasma and total GSH levels in occipital white matter (measured by single-voxel MR spectroscopy).
- Occurrence of serious adverse events [ Time Frame: Measurements will be obtained at baseline, 3months, 6months, 9months, 12months ]The investigators do not expect any participants to develop hypercalcemia (serum calcium >10.7mg/dl) or related serious adverse events (e.g. kidney stones) while taking 2000 IU or 4000 IU daily.
- Change in plasma interleukin-8 levels [ Time Frame: Measurements a baseline and 12 months ]The investigators expect a decrease in plasma IL-8 levels between baseline and 12 months
- Change in plasma macrophage inflammatory protein-1b levels [ Time Frame: Measurements at baseline and 12 months ]The investigators expect a decrease in plasma MIP-1b levels between baseline and 12 months
- Change in plasma monocyte chemoattractant protein-1 levels [ Time Frame: Measurements at baseline and 12 months ]The investigators expect a decrease in plasma MCP-1 levels between baseline and 12 months
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02595489
|United States, California|
|Palo Alto, California, United States, 94304|
|Contact: Keith Van Haren, MD firstname.lastname@example.org|
|Principal Investigator: Keith Van Haren, MD|
|Principal Investigator:||Keith Van Haren, MD||Stanford University|