X-linked AdrenoleukodystrophyPhase 1NCT02595489
A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy
A Phase 1 study testing vitamin D3 in people with X-linked Adrenoleukodystrophy, run by Stanford University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 months to 25 years, men only
- Conditions the study is for
- X-linked Adrenoleukodystrophy
- What is being tested?
- vitamin D3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Nov 2016to 30 Jun 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 months to 25 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
None listed.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- vitamin D3
- Keywords
- Leukodystrophy, ABCD1, Demyelination, Inflammation, ALD, Vitamin D, Oxidative Stress, X- linked, Adrenoleukodystrophy
- Medical subject headings
- Adrenoleukodystrophy, Demyelinating Diseases, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vitamin D3Dietary supplement
Also called vitamin D
Daily oral supplement provided by study investigators
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: vitamin D3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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
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.
Measured: 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.
The investigators expect a decrease in whole blood protein carbonyl levels between baseline and 12 months.
Measured: Measurements at baseline and 12months
Correlation between plasma 25-OH vitamin D and intracellular glutathione levels in peripheral monocytes
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.
Measured: Measurements at baseline and 12 months
Change in glutathione (GSH) levels in blood
The investigators expect a positive correlation between plasma 25-OH vitamin levels and GSH levels in whole blood (measured by tandem mass spectroscopy).
Measured: Measurements will be obtained at baseline, 6months, and 12months
Change in glutathione (GSH) levels in brain
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).
Measured: Measurements will be obtained at baseline, 6months, and 12months
Occurrence of serious adverse events
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.
Measured: Measurements will be obtained at baseline, 3months, 6months, 9months, 12months
Change in plasma interleukin-8 levels
The investigators expect a decrease in plasma IL-8 levels between baseline and 12 months
Measured: Measurements a baseline and 12 months
Change in plasma macrophage inflammatory protein-1b levels
The investigators expect a decrease in plasma MIP-1b levels between baseline and 12 months
Measured: Measurements at baseline and 12 months
Change in plasma monocyte chemoattractant protein-1 levels
The investigators expect a decrease in plasma MCP-1 levels between baseline and 12 months
Measured: Measurements at baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2015 (estimated)
- Study start21 Nov 2016
- Primary completion30 Jun 2020
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for X-linked AdrenoleukodystrophyStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- single-arm dose escalation
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Hugo W. Moser Research Institute at Kennedy Krieger, Inc., ALD Connect, Inc.
- Responsible party
- Principal investigator, Keith Van Haren, Stanford University
- Investigators
- Keith Van Haren, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02595489
- Sponsor's protocol ID
- 23596
- Other IDs
- K23NS087151
- Status last verified
- Jun 2022
- First submitted
- 29 Oct 2015
- Last updated
- 9 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified data will be made available to clinical investigators upon reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy
- ClinicalTrials.gov ID
- NCT02595489
- Acronym / sponsor ID
- 23596
- Conditions
- X-linked Adrenoleukodystrophy
- Keywords
- Leukodystrophy, ABCD1, Demyelination, Inflammation, ALD, Vitamin D, Oxidative Stress, X- linked
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Hugo W. Moser Research Institute at Kennedy Krieger, Inc., ALD Connect, Inc.
- Study start
- 21 Nov 2016 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 3 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single-arm dose escalation
| Arm | Type | Receives |
|---|---|---|
| Vitamin D3 | Experimental | Dietary Supplement: vitamin D3Single-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. |
Who may qualify
- Ages
- 18 months to 25 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vitamin D3Also: vitamin DDaily oral supplement provided by study investigators | Dietary supplement | Vitamin D3 |
Primary outcome
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)
9 secondary outcomes
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.
Change in protein carbonyl levels in whole blood at baseline and 12 months.
Time frame: Measurements at baseline and 12months
Correlation between plasma 25-OH vitamin D and intracellular glutathione levels in peripheral monocytes
Time frame: Measurements at baseline and 12 months
Change in glutathione (GSH) levels in blood
Time frame: Measurements will be obtained at baseline, 6months, and 12months
Change in glutathione (GSH) levels in brain
Time frame: Measurements will be obtained at baseline, 6months, and 12months
Occurrence of serious adverse events
Time frame: Measurements will be obtained at baseline, 3months, 6months, 9months, 12months
Change in plasma interleukin-8 levels
Time frame: Measurements a baseline and 12 months
Change in plasma macrophage inflammatory protein-1b levels
Time frame: Measurements at baseline and 12 months
Change in plasma monocyte chemoattractant protein-1 levels
Time frame: Measurements at baseline and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2022.
- Stanford University Neurosciences Patient Registry for Clinical TrialsLink provided by the sponsor.
- Multiple Sclerosis and Neuroimmunology Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Deidentified data will be made available to clinical investigators upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith Van Haren, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing vitamin D3 in people with X-linked Adrenoleukodystrophy, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2022.