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

NCT ID: NCT02595489

Last Updated: 2022-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-21
• Study Completion Date: 2020-06-30

Brief 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.

Conditions

X-linked Adrenoleukodystrophy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Vitamin D3

Single-arm, dose-escalation starting at 1,000 IU or 2,000 IU of vitamin D3 daily for a 6 month period, followed by a conditional titration up to 4,000 IU daily for at least 6 months thereafter. No placebo.

Group Type: EXPERIMENTAL

vitamin D3

Intervention Type: DIETARY_SUPPLEMENT

Daily oral supplement provided by study investigators

Interventions

vitamin D3

Daily oral supplement provided by study investigators

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

vitamin D

Eligibility Criteria

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

• Minimum Eligible Age: 18 Months
• Maximum Eligible Age: 25 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

OTHER

Sponsor Role: collaborator

ALD Connect, Inc.

INDUSTRY

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Keith Van Haren

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Keith Van Haren, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Palo Alto, California, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Related Links

https://redcap.stanford.edu/surveys/?s=kCXDqU

Stanford University Neurosciences Patient Registry for Clinical Trials

http://med.stanford.edu/neurology/divisions/neuroimmunology/clinicaltrials.html

Multiple Sclerosis and Neuroimmunology Clinical Trials

Other Identifiers

K23NS087151

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23596

Identifier Type: -

Identifier Source: org_study_id