Sickle Cell Disease
Conditions
Keywords
Bolus supplementation, Pilot randomised controlled trial, Vitamin D
Brief summary
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
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).
Interventions
DIETARY_SUPPLEMENTVitamin D bolus
One single oral liquid vitamin D3 supplement of 300 000 IU
DIETARY_SUPPLEMENTPlacebo
Placebo identical in taste and appearance to the vitamin D bolus
Sponsors
Euro-Pharm
St. Justine's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The Applied Clinical Research Unit of Sainte-Justine UHC will generate the randomisation scheme. Group allocation codes will be held in a secure location with a restricted access by the Central pharmacy (Sainte-Justine UHC). All participants and research personnel, including the nurse, research trainee and research team will be blinded to group assignment. The supplier Euro-Pharm will provide the placebo and vitamin D3 preparations in coded bottles. Pharmacy will prepare the 6-mL bolus in coded syringes following the randomisation scheme.
Intervention model description
This is a randomised, quadruble-blind, placebo-controlled, parallel-group trial of vitamin D3 bolus supplementation.
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change in total serum 25-hydroxyvitamin D levels | 3 months | Group difference in the mean change in total serum 25OHD from baseline to 3 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vitamin D sufficiency | 3 months | Difference in the proportion of children with serum 25-hydroxyvitamin D ≥75nmol/L at 3 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hypercalcemia | 3 months | Number of patients with serum calcium above normal reference range for age |
| Serum 25-hydroxyvitamin D levels | 3 months | Number of patients with serum 25-hydroxyvitamin D levels \>250 nmol/L |
| Mean change in weight | 3 months | Group difference in the mean change of weight (kg) from baseline to 3 months. |
| Mean change in height | 3 months | Group difference in the mean change of height (kg) from baseline to 3 months. |
| Mean change in hemoglobin | 3 months | Group difference in the mean change of circulating hemoglobin from baseline to 3 months. |
| Mean change in fetal hemoglobin | 3 months | Group difference in the mean change of circulating fetal hemoglobin from baseline to 3 months. |
| Mean change in leucocyte counts | 3 months | Group difference in the mean change of blood leucocyte counts from baseline to 3 months. |
| Mean change in platelet counts | 3 months | Group difference in the mean change of blood platelet counts from baseline to 3 months. |
| Mean change in reticulocyte counts | 3 months | Group difference in the mean change of blood reticulocyte counts from baseline to 3 months |
| Mean change in neutrophil counts | 3 months | Group difference in the mean change of blood neutrophil counts from baseline to 3 months |
| Mean change in quality of life scores | 3 months | Health-related quality of life will be assessed through the Pediatric Quality of life (PedQoL) inventory. Group difference in the mean change in PedQoL scores. |
| Mean change in serum creatinine | 3 months | Group difference in the mean change of serum creatinine from baseline to 3 months. |
| Mean change in serum bilirubin | 3 months | Group difference in mean change of serum bilirubin from baseline to 3 months. |
| Mean change in serum parathyroid hormone | 3 months | Group difference in mean change of serum parathyroid hormone from baseline to 3 months |
| Mean change in serum P1NP | 3 months | Group difference in mean change of serum amino-terminal propeptide of type I collagen (P1NP) from baseline to 3 months |
| Mean change in serum C-telopeptides | 3 months | Group difference in mean change of serum C-telopeptides from baseline to 3 months |
| Mean change in musculoskeletal pain scores | 3 months | Musculoskeletal pain will be assessed with the Brief Pain Inventory (BPI). Group difference in the mean change in BPI scores. |
| Sickle cell disease-related complications | 3 months | Occurrence of sickle cell disease complications affecting bone, the kidneys, the retina, blood vessels, the heart, the lungs, the spleen, the liver and gallbladder during the study period |
| Participant recruitment | 3 months | Percentage of patients recruited from those screened |
| Participant retention | 3 months | Percentage of patients retained for the entire study duration |
| Participant compliance | 3 months | Percentage of patients who comply with the study protocol |
| Mean change in mean corpuscular volume | 3 months | Group difference in the mean change of blood mean corpuscular volume from baseline to 3 months |
| Hypercalciuria | 7 days post-intervention | Number of patients with urinary calcium to creatinine ratio above normal reference range for age |
Countries
Canada
Outcome results
None listed