Vitamin D Supplementation in Children With Sickle Cell Disease

Study Overview
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Brief Summary
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Sickle cell disease (SCD) is a genetic disease characterized by abnormal hemoglobin, the main constituent of red blood cells. People with SCD have nutritional deficiencies, and vitamin D deficiency is one of the most common. Symptoms of vitamin D deficiency are similar to those of SCD and include chronic pain and bone complications. Correcting vitamin D nutrition of children with SCD represents a treatment that will improve their health. A single oral high-dose of vitamin D3 will be given to SCD children during one of their follow-up visits at the SCD clinic of CHU Sainte-Justine, Montreal, Canada. This mode of administration was chosen to ensure a better adherence to the treatment. The investigators will determine whether this dose is safe and its administration feasible in clinic. The impact of this dose on blood vitamin D and calcium, urinary calcium, growth, inflammation, bone health, pain and quality of life will also be assessed. This study intends to propose a new intervention to improve the nutrition of children with this disease.

Detailed Description
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Vitamin D deficiency is one of the most common nutritional conditions among patients with sickle cell disease (SCD). Since vitamin D deficiency and SCD share common manifestations including chronic pain, poor bone health and chronic systemic inflammation, it is reasonable to postulate that vitamin D deficiency may contribute to these complications. Thus, optimizing vitamin D nutrition represents an inexpensive strategy that may improve vitamin D status and health outcomes in SCD children. The working hypothesis is that administration of a single oral bolus of 300,000 IU of vitamin D3 to SCD children will result in the attainment of vitamin D sufficiency (25OHD levels >75 nmol/L) in 80% of participants after 3 months. The primary objectives are to assess feasibility, acceptability, and safety of the vitamin D3 bolus while secondary objectives are related to the mean change in serum 25OHD from baseline to 3 months post-bolus and its clinical impact. Seventy-two SCD children (5-17 years, SS and SC genotypes) will be randomized to one bolus of 300,000 IU of vitamin D3 or identical placebo. Blood will be collected at baseline and 3-month post-bolus to measure serum 25OHD and calculate the change from baseline at 3 months (efficacy outcomes). Other outcomes include urinary calcium/creatinine ratio and serum calcium (safety), questionnaires (acceptability and musculoskeletal pain) and parameters related to growth, haematology, inflammation and bone health (exploratory outcomes).

Official Title
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Vitamin D Intervention in Children With Sickle Cell Disease: A Pilot Randomized Controlled Trial

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Dietary Supplement: Vitamin D bolus
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged between 5 and 17 years old who are followed up at the SCD Clinic, CHU Sainte-Justine, Montreal, Canada. Exclusion Criteria: Conditions or use of medications known to interfere with calcium or vitamin D absorption or metabolism Known hypercalcemia Conditions characterized by a hypersensitivity to vitamin D (e.g. granulomatous disorders) Patients clinically diagnosed with rickets or other conditions requiring vitamin D therapy History or presence of urolithiasis Anticipated difficult follow up Patients already enrolled in other investigational studies Patients who have recently been hospitalized for severe pain crisis or acute sickle complication in the past 2 weeks Patients with unresolved pain issues

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomised, quadruble-blind, placebo-controlled, parallel-group trial of vitamin D3 bolus supplementation.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo identical to the vitamin D bolus in taste and appearance. The placebo will be administered once, at the beginning of the study. The oral liquid placebo will be prepared at the Pharmacy in coded syringes and will be administered to the participants by a nurse at the sickle cell disease Clinic. | Dietary Supplement: Placebo<br>* Placebo identical in taste and appearance to the vitamin D bolus<br>|
| Experimental: Vitamin D bolus<br>The vitamin D bolus is an oral liquid supplement that will be administered once, at the beginning of the study. The oral liquid vitamin D bolus will be prepared at the Pharmacy in coded syringes and will be administered to the participants by a nurse at the sickle cell disease Clinic.The dose of vitamin D3 contained in the bolus is 300 000 IU. | Dietary Supplement: Vitamin D bolus<br>* One single oral liquid vitamin D3 supplement of 300 000 IU<br>* Other names: Cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in total serum 25-hydroxyvitamin D levels | Group difference in the mean change in total serum 25OHD from baseline to 3 months. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitamin D sufficiency | Difference in the proportion of children with serum 25-hydroxyvitamin D ≥75nmol/L at 3 months | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bolus supplementation, Pilot randomised controlled trial, Vitamin D