Vitamin D Supplementation in Children With Sickle Cell Disease

Study Overview
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Brief Summary
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Children aged 6 months to 12 years of age will be randomised to receive vitamin D 60,000IU once a month for 3 months or a placebo. The vitamin D will be in form of granules supplied in sachets. The primary study outcomes will be incidence of hospitalisation and change in vitamin D levels following supplementation. Secondary outcomes will include incidence of vaso-occlusive crisis (VOC), acute severe respiratory illness, Vitamin D related Severe adverse events and requirements for blood transfusion

Detailed Description
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BACKGROUND: More than 75% of all children with sickle cell anemia (SCA) are born in sub-Saharan Africa annually. The hallmark of SCA is haemolytic anaemia and or pain crisis that often require hospitalisation. Interventions to reduce the complications, which are prerequisites for frequent hospitalisations, are needed urgently. Vitamin D deficiency is common in children with SCA and is associated with recurrent vaso-occlusive crisis, blood transfusion, hospitalisation and infections. Routine vitamin D supplementation is not practiced in the care of sickle cell disease patients yet it has been associated with improved bone health and bone mineral density, reduced chronic pain and improved quality of life. HYPOTHESIS: Vitamin D supplementation will lead to a lower incidence of hospitalisation than placebo in Ugandan children with SCA. METHODS: The study will be a randomized, placebo-controlled, double blind clinical trial in which 331 Ugandan children with SCA aged 6 months to 12 years inclusive will receive vitamin D (60,000IU granules monthly) and another 331 a placebo (identical to vitaminD in appearance) for 3 months. The primary study outcome will be incidence of hospitalisation. Secondary outcomes will include incidence of vaso-occlusive crisis (VOC), acute severe respiratory illness, Vitamin D related Severe adverse events and requirements for blood transfusion IMPACT: If this trial shows a reduction in hospitalisation, it will be the basis for a multi-site pre-post intervention clinical trial to assess real-world safety and efficacy of Vitamin D in African children with SCA. The monthly administration is easy, and since vitamin D is inexpensive, this trial has the potential to improve the health of hundreds/ thousands of African children with SCA through reduction of infection-related morbidity and mortality.

Official Title
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Effect of Vitamin D Supplementation on Sickle Cell Disease Hospitalisation and Related Complications Among Children in Mulago Hospital: A Randomised Clinical Trial

Conditions
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Children With Sickle Cell Disease at Mulago Hospital

Intervention / Treatment
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* Dietary Supplement: Vitamin D3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented sickle cell disease (HbSS supported by hemoglobin electrophoresis results) attending Mulago Hospital Sickle Cell Clinic) Age range of 6 months to 12 years, inclusive, at the time of enrolment Weight at least 5.0 kg at the time of enrolment Willingness to comply with all study-related treatments, evaluations, and follow-up Exclusion Criteria: Known other chronic medical condition (e.g., HIV, malignancy, Renal & liver disease, active clinical tuberculosis) Severe acute malnutrition determined by impaired growth parameters as defined by WHO weight for length/height less than -3SD. Evidence of Vitamin D supplementation in the past one month (by prescription or drug sample)

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 12 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 331 children will be randomised to the intervention and another 331 to the placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D supplement<br>331 children will each received 60,000IU of vitamin D once a month for 3 months. | Dietary Supplement: Vitamin D3<br>* Vitamin D3 supplement<br>|
| Active Comparator: Intervention<br>The intervention arm will receive vitamin D3. | Dietary Supplement: Vitamin D3<br>* Vitamin D3 supplement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of hospitalisation among children with SCD supplemented with vitamin D versus placebo. | Number of children hospitalised during the follow up period and number of hospitalisations per child | 3 months follow up | 
| Effect of vitamin supplementation on serum levels of 25 Hydroxyvitamin D levels in children with SCD | Serum levels of 25 Hydroxyvitamin D | 3 months follow up | 
| Frequency of blood transfusion among children supplemented with vitamin D versus Placebo in children with sickle cell anaemia | The number of children requiring blood transfusion during follow up and the episodes per child | 3 months follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of vaso-occlusive crises (VOC) | Incidence of painful vaso-occlusive crises | 3 months follow up | 
| Incidence of acute severe respiratory illnesses | Incidence of cough associated with difficult breathing confirmed as pneumonia or acute chest syndrome by a health worker | 3 months follow up | 
| Severe adverse events | Serious adverse events for example severe diarrhoea and vomiting with dehydration. | 3 months follow up |