Rapid Vitamin D Supplementation for Vitamin D Deficiency

(VITdALIZE-KIDS Trial)

No longer recruiting at 10 trial locations

Overseen By Katie O'Hearn, MSc

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Hospital of Eastern Ontario

Must not be taking: Thiazide diuretics, Digoxin

Disqualifiers: Hypercalcemia, William's syndrome, Nephrolithiasis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a rapid high dose of vitamin D can improve survival and quality of life in critically ill children with vitamin D deficiency. Participants will receive either a single high dose of vitamin D3 (Cholecalciferol) or a placebo (a harmless pill with no active drug) through random assignment. The trial targets children in pediatric intensive care units (PICUs) identified with vitamin D deficiency. Researchers seek to discover if quickly boosting vitamin D levels aids in better recovery for these children. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on digoxin-therapy or thiazide diuretics with high calcium supplementation, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking high doses of vitamin D, like the one used in this trial, is generally safe. An earlier trial with similar vitamin D doses found no serious side effects. Another study found that a large dose of vitamin D greatly reduced hospital deaths in patients with very low vitamin D levels. Most participants in these studies did not experience major problems, though a small number (1.9% to 18.5%) did encounter minor side effects. Overall, high-dose vitamin D appears to be well-tolerated and could benefit people with low vitamin D levels, especially those who are very sick. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard vitamin D supplements, which typically require continuous daily dosing, the treatment being explored here involves a single high dose of cholecalciferol. Researchers are excited about this approach because it could simplify the management of vitamin D deficiency by potentially offering quicker and more sustained improvement in vitamin D levels. This could be particularly beneficial for patients who struggle with daily compliance, making it a convenient and efficient option.

What evidence suggests that rapid vitamin D supplementation might be an effective treatment for vitamin D deficiency in critically ill children?

Studies have shown that vitamin D is crucial for maintaining strong bones, proper muscle function, and overall health. Research indicates that correcting a vitamin D deficiency can strengthen bones and help prevent falls and fractures. In very sick patients, insufficient vitamin D has been linked to worse health outcomes. Evidence suggests that adequate vitamin D levels can improve symptoms and quality of life. In this trial, some participants will receive a rapid increase in vitamin D levels with cholecalciferol (vitamin D3) to quickly restore these levels, potentially improving survival rates and health in very sick children. Other participants will receive a placebo for comparison. ^{2 6 7 8 9}

Who Is on the Research Team?

Dayre McNally, MD, PhD

Principal Investigator

Children's Hospital of Eastern Ontario

Are You a Good Fit for This Trial?

This trial is for critically ill children in Canadian PICUs, aged from 37 weeks corrected gestational age to 18 years old, who have a confirmed vitamin D deficiency. It's not suitable for those expected to leave the PICU within three days of enrollment or with certain medical conditions like severe liver failure, hypercalcemia, or allergies to vitamin D.

Inclusion Criteria

I am currently admitted to the Pediatric Intensive Care Unit.

Vitamin D deficiency, as defined by blood 25OHD < 50 nmol/L at the time of screening

Exclusion Criteria

I have severe liver failure.

Previous enrollment in this trial

My doctor has advised against me joining this trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive a single dose of high-dose vitamin D3 or placebo at enrollment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up measurements at 28 and 90 days

90 days

2 visits (in-person or by telephone)

What Are the Treatments Tested in This Trial?

Interventions

• Cholecalciferol
• Placebo

Trial Overview

The study tests if high-dose Vitamin D3 (cholecalciferol) can improve survival and quality of life in vitamin D deficient critically ill children compared to a placebo. Participants will receive either one dose of Vitamin D3 up to 400,000 IU or no drug and be monitored for health changes over 90 days.

How Is the Trial Designed?

Group I: Vitamin D Experimental Treatment 1 Intervention

Approximately half of the subjects randomized into VITdALIZE-KIDS will be randomized into the Vitamin D Group and will receive a single dose of cholecalciferol at enrolment. Participants may also receive standard vitamin D dosing at the discretion of the care team (e.g. 400-1000 IU/day).

Group II: Placebo Placebo Group 1 Intervention

Approximately half of the subjects randomized into VITdALIZE-KIDS will be randomized into the Placebo Group and will receive a single dose of placebo at enrolment. Participants may also receive standard vitamin D dosing at the discretion of the care team (e.g. 400-1000 IU/day).

Cholecalciferol is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Vitamin D3 for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in European Union as Cholecalciferol for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in Canada as Vitamin D3 for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in Japan as Cholecalciferol for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in China as Vitamin D3 for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in Switzerland as Cholecalciferol for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Who Is Running the Clinical Trial?

Children's Hospital of Eastern Ontario

Lead Sponsor

Trials

134

Recruited

61,000+

EURO-PHARM International Canada, Inc.

Collaborator

Trials

2

Recruited

750+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Canadian Critical Care Trials Group

Collaborator

Trials

32

Recruited

227,000+

Published Research Related to This Trial

In a pilot study of 21 healthy volunteers taking 2000 IU/day of Vitamin D (VD) for one month, 95% had insufficient VD levels at the start, but this dropped to 62% after supplementation, indicating significant improvement in VD status.

The study found that plasma VD levels increased by a median of 3.09 ng/mL after 7 days and 8.85 ng/mL after 28 days, suggesting that ongoing supplementation is necessary to achieve optimal VD levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monthly Increase in Vitamin D Levels upon Supplementation with 2000 IU/Day in Healthy Volunteers: Result from "Integriamoci", a Pilot Pharmacokinetic Study. Avataneo, V., Palermiti, A., De Nicolò, A., et al.[2022]

In a study using mice, inducing a state of 25-hydroxyvitamin D deficiency did not affect the vulnerability of dopaminergic neurons to the neurotoxin MPTP, suggesting that low vitamin D levels may not increase the risk of neuronal damage in this model of Parkinson's disease.

The research showed no significant differences in dopamine levels or key protein expressions related to dopamine production between vitamin D-deficient and control mice after exposure to the neurotoxin, indicating that 25(OH)D deficiency may not play a critical role in the neurodegenerative processes associated with Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

25-Hydroxyvitamin D depletion does not exacerbate MPTP-induced dopamine neuron damage in mice. Dean, ED., Mexas, LM., Cápiro, NL., et al.[2021]

A study involving 53 healthy young adults found that a new soft capsule formulation of vitamin D3 (100,000 IU) significantly increased serum 25-hydroxyvitamin D levels compared to a traditional oral solution, demonstrating a superior pharmacokinetic profile.

The soft capsule formulation not only reached higher peak levels of vitamin D3 more quickly but also maintained serum levels between 20 and 30 ng/mL for four months, indicating its potential effectiveness in addressing vitamin D deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of a New Pharmaceutical Form of Vitamin D3 100,000 IU in Soft Capsule. Mentaverri, R., Souberbielle, JC., Brami, G., et al.[2020]

In a study involving 40 healthy participants, both vitamin D2 and D3, when consumed at low doses (5 or 10 μg/d), significantly increased serum levels of their respective metabolites (25-OH-D2 and 25-OH-D3) over a 4-week period with minimal UV-B exposure.

The results indicated that vitamin D2 and D3 are equally effective in raising serum 25-hydroxy-vitamin D levels, suggesting that either form can be used to improve vitamin D status in individuals with low UV-B exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fortified malted milk drinks containing low-dose ergocalciferol and cholecalciferol do not differ in their capacity to raise serum 25-hydroxyvitamin D concentrations in healthy men and women not exposed to UV-B. Fisk, CM., Theobald, HE., Sanders, TA.[2018]

In a study of 192 children with vitamin D deficiency, monthly administration of vitamin D3 (25,000 IU every 4 weeks) significantly increased serum vitamin D levels compared to daily dosing (1,000 IU), with 78.1% of the monthly group achieving sufficient levels above 20 ng/mL.

The monthly regimen was found to be safe, with no cases of hypercalcemia reported, suggesting that it may enhance compliance and be an effective alternative for treating vitamin D deficiency in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monthly versus daily administration of vitamin D3 in children: a retrospective propensity score-matched study. Choi, J., Choe, Y., Yang, S.[2023]

A single monthly dose of 60,000 IU of cholecalciferol (vitamin D) significantly increased serum 25-hydroxyvitamin D levels in healthy school children from an average of 12.04 ng/mL to 32.6 ng/mL over 12 months (p<0.001).

The supplementation was found to be safe, as none of the 118 children developed hypercalcemia, indicating that this regimen is both effective and safe for achieving vitamin D sufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a single monthly dose of cholecalciferol in healthy school children. Kuchay, MS., Jevalikar, GS., Mithal, A., et al.[2018]

A daily oral dose of 20 μg of vitamin D3 significantly improved vitamin D status in participants, with serum 25(OH)D3 levels increasing from 38 nmol/L at baseline to 73 nmol/L after 12 weeks, indicating effective supplementation.

94% of participants receiving vitamin D3 reached sufficient levels of 25(OH)D3 (≥50 nmol/L), demonstrating the efficacy of this dosage in addressing vitamin D deficiency, especially during winter months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D3 supplementation: Response and predictors of vitamin D3 metabolites - A randomized controlled trial. Lehmann, U., Riedel, A., Hirche, F., et al.[2017]

A study of 306 patients treated with ergocalciferol (vitamin D2) showed that regimens providing over 600,000 IU were most effective, achieving vitamin D sufficiency in 64% of cases without causing toxicity.

Common regimens like 50,000 IU weekly or monthly increased vitamin D levels significantly, but only 38% to 82% of patients reached sufficiency, highlighting the need for better treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of vitamin D repletion regimens to correct vitamin D status in adults. Pepper, KJ., Judd, SE., Nanes, MS., et al.[2021]

Many randomized controlled trials (RCTs) on vitamin D have not confirmed health benefits seen in observational studies, likely due to inappropriate study designs that do not account for the non-linear relationships between vitamin D levels and health outcomes.

The authors suggest a new hybrid observational approach for vitamin D RCTs that focuses on individual serum 25-hydroxyvitamin D (25(OH)D) levels, emphasizing the need to measure and adjust vitamin D supplementation based on these levels to better assess health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why vitamin D clinical trials should be based on 25-hydroxyvitamin D concentrations. Grant, WB., Boucher, BJ., Bhattoa, HP., et al.[2022]

Daily supplementation of 200 mL of milk fortified with 240 IU of vitamin D2 significantly increased serum 25(OH)D levels in children compared to plain milk, indicating some efficacy in improving vitamin D status.

Despite the increase, the fortified milk did not raise serum 25(OH)D levels to sufficient levels for many children, highlighting that the dosage may be inadequate for addressing vitamin D deficiency in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Daily Supplementation of Milk Fortified With Vitamin D2 for Three Months in Healthy School Children: A Randomized Placebo Controlled Trial. Marwaha, RK., Dabas, A., Puri, S., et al.[2021]

A single oral dose of 300,000 IU of cholecalciferol or two consecutive doses totaling 600,000 IU can significantly raise vitamin D levels in patients with deficiencies, with nearly all participants achieving levels above 20 ng/mL within one week.

The study, involving 160 inpatients with varying degrees of vitamin D deficiency, found no signs of toxicity from high-dose supplementation, suggesting it is a safe and effective strategy for addressing vitamin D deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of single or consecutive double high-dose oral cholecalciferol supplementation in adult patients with vitamin D deficiency. Yilmaz, R.[2023]

In a study involving 100 patients with mild to moderate vitamin D deficiency, those treated with cholecalciferol (vitamin D3) showed significant short-term improvement in fibromyalgia assessment scores compared to the placebo group.

However, severely deficient patients did not experience symptom improvement after treatment, indicating that while vitamin D supplementation may help some, it may not be effective for all levels of deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial. Arvold, DS., Odean, MJ., Dornfeld, MP., et al.[2022]

Citations

1.

ods.od.nih.gov

ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

Vitamin D - Health Professional Fact Sheet

In adults and adolescents, vitamin D deficiency can lead to osteomalacia, in which existing bone is incompletely or defectively mineralized ...

2.

academic.oup.com

academic.oup.com/edrv/article/45/5/625/7659127

Consensus Statement on Vitamin D Status Assessment and ...

Clinical Outcomes of Vitamin D Deficiency. Skeletal Outcomes. Skeletal outcomes of vitamin D deficiency are summarized in Fig. 3. Vitamin D ...

3.

frontiersin.org

frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1579957/full

Cholecalciferol (vitamin D3): efficacy, safety, and ...

It is important to perceive vitamin D deficiency to prevent possible fractures or falls (2). The most common are loss of mobility, grip strength and muscle mass ...

4.

nature.com

nature.com/articles/s41574-021-00593-z

The health effects of vitamin D supplementation: evidence ...

These data indicate that correction of severe vitamin D deficiency might improve bone density, but not when given to vitamin D-replete people.

5.

jhpn.biomedcentral.com

jhpn.biomedcentral.com/articles/10.1186/s41043-025-00881-8

Effects of vitamin D supplementation on symptoms and clinical ...

The majority of participants who achieved vitamin D levels > 50 nmol/L experienced complete improvement in their symptoms; when levels were ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12183072/

Cholecalciferol (vitamin D3): efficacy, safety, and ...

Standard-dose vitamin D supplementation (2,000–4,000 IU/day) is generally considered safe and well-tolerated, with minimal risk of adverse effects. However, ...

7.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK532266/

Vitamin D Deficiency - StatPearls - NCBI Bookshelf

Deficiency can lead to various complications, most notably rickets in children and osteoporosis in adults. Milk fortification with vitamin D in ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02868827

Cholecalciferol Supplementation in Critically Ill Patients ...

A recent RCT has demonstrated 50% reduction in hospital mortality in patients with severe vit.D deficiency following a single high dose of cholecalciferol ( ...

9.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2405457721003338

Safety and effectiveness of vitamin D mega-dose

Serum vitamin D levels were normalized between 70 and 100% of patients, and adverse effects ranged between 1.9 and 18.5%. Conclusion. The study demonstrated ...