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

NCT02595489 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 23596K23NS087151
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

X-linked Adrenoleukodystrophy

Keywords

Leukodystrophy; ABCD1; Demyelination; Inflammation; ALD; Vitamin D; Oxidative Stress; X- linked; Adrenoleukodystrophy

Outcome Measures

Primary Outcomes (2)

• Percent of patients with a plasma 25-OH vitamin D level in the target range (40-80ng/ml) 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)

  Plasma 25-OH vitamin D will be measured at 12 months

• Percent of patients with a plasma 25-OH vitamin D level in the target range (40-80ng/ml) 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)

  Plasma 25-OH vitamin D will be measured at 6 months

Secondary Outcomes (9)

• Correlation between appearance of gadolinium enhancing brain lesion on MRI and most recent plasma 25-OH vitamin D level

  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.

• Change in protein carbonyl levels in whole blood at baseline and 12 months.

  Measurements at baseline and 12months

• Correlation between plasma 25-OH vitamin D and intracellular glutathione levels in peripheral monocytes

  Measurements at baseline and 12 months

• Change in glutathione (GSH) levels in blood

  Measurements will be obtained at baseline, 6months, and 12months

• Change in glutathione (GSH) levels in brain

  Measurements will be obtained at baseline, 6months, and 12months

Study Arms (1)

Vitamin D3

EXPERIMENTAL

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.

Dietary Supplement: vitamin D3

Interventions

vitamin D3 DIETARY_SUPPLEMENT

Daily oral supplement provided by study investigators

Also known as: vitamin D

Vitamin D3

Eligibility Criteria

• Age: 18 Months - 25 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.: collaborator
• ALD Connect, Inc.: collaborator

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

Location

Related Links

• Stanford University Neurosciences Patient Registry for Clinical Trials
• Multiple Sclerosis and Neuroimmunology Clinical Trials

MeSH Terms

Conditions

Adrenoleukodystrophy; Demyelinating Diseases; Inflammation

Interventions

Cholecalciferol; Vitamin D

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Keith Van Haren, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: single-arm dose escalation

Study Record Dates

• First Submitted: October 29, 2015
• First Posted: November 3, 2015
• Study Start: November 21, 2016
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: June 9, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: For up to 10 years following study completion
• Access Criteria: Reasonable request via email to study PI (kpv@stanford.edu)

Locations

US (1)