Children With Sickle Cell Disease at Mulago Hospital
Conditions
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTVitamin D3
Vitamin D3 supplement
Sponsors
Makerere University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The sachets containing vitamin D will be exactly similar to the ones containing the placebo. Both the intervention and placebo granules will be identical in colour, odour, taste and amount. Children will be randomized into treatment groups by order of entry in the study, based on a pre-determined blinded randomization list created and managed by an independent statistician.
Intervention model description
331 children will be randomised to the intervention and another 331 to the placebo.
Eligibility
Sex/Gender
ALL
Age
6 Months to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Documented sickle cell disease (HbSS supported by hemoglobin electrophoresis results) attending Mulago Hospital Sickle Cell Clinic) 2. Age range of 6 months to 12 years, inclusive, at the time of enrolment 3. Weight at least 5.0 kg at the time of enrolment 4. Willingness to comply with all study-related treatments, evaluations, and follow-up
Exclusion criteria
1. Known other chronic medical condition (e.g., HIV, malignancy, Renal & liver disease, active clinical tuberculosis) 2. Severe acute malnutrition determined by impaired growth parameters as defined by WHO weight for length/height less than -3SD. 3. Evidence of Vitamin D supplementation in the past one month (by prescription or drug sample)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of hospitalisation among children with SCD supplemented with vitamin D versus placebo. | 3 months follow up | Number of children hospitalised during the follow up period and number of hospitalisations per child |
| Effect of vitamin supplementation on serum levels of 25 Hydroxyvitamin D levels in children with SCD | 3 months follow up | Serum levels of 25 Hydroxyvitamin D |
| Frequency of blood transfusion among children supplemented with vitamin D versus Placebo in children with sickle cell anaemia | 3 months follow up | The number of children requiring blood transfusion during follow up and the episodes per child |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of vaso-occlusive crises (VOC) | 3 months follow up | Incidence of painful vaso-occlusive crises |
| Incidence of acute severe respiratory illnesses | 3 months follow up | Incidence of cough associated with difficult breathing confirmed as pneumonia or acute chest syndrome by a health worker |
| Severe adverse events | 3 months follow up | Serious adverse events for example severe diarrhoea and vomiting with dehydration. |
Contacts
Primary ContactGrace Ndeezi, PhD
Backup ContactRuth Namazzi, MMED
Outcome results
None listed