Clinical trial NCT03417947: Vitamin D Supplementation in Children With Sickle Cell Disease
Official title: Vitamin D Intervention in Children With Sickle Cell Disease: A Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sickle Cell Disease
Keywords: Bolus supplementation
Pilot randomised controlled trial
Vitamin D
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
Collaborators: name: Euro-Pharm
First posted: 2018-01-31
Enrollment: 42
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomised, quadruble-blind, placebo-controlled, parallel-group trial of vitamin D3 bolus supplementation.
Primary purpose: OTHER

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).

Eligibility criteria: 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

Primary outcomes:
measure: Mean change in total serum 25-hydroxyvitamin D levels
timeFrame: 3 months
Secondary outcomes:
measure: Vitamin D sufficiency
timeFrame: 3 months
Other outcomes:
measure: Hypercalciuria
timeFrame: 7 days post-intervention
measure: Hypercalcemia
timeFrame: 3 months
measure: Serum 25-hydroxyvitamin D levels
timeFrame: 3 months
measure: Mean change in weight
timeFrame: 3 months
measure: Mean change in height
timeFrame: 3 months
measure: Mean change in hemoglobin
timeFrame: 3 months
measure: Mean change in fetal hemoglobin
timeFrame: 3 months
measure: Mean change in leucocyte counts
timeFrame: 3 months
measure: Mean change in platelet counts
timeFrame: 3 months
measure: Mean change in reticulocyte counts
timeFrame: 3 months
measure: Mean change in neutrophil counts
timeFrame: 3 months
measure: Mean change in mean corpuscular volume
timeFrame: 3 months
measure: Mean change in serum creatinine
timeFrame: 3 months
measure: Mean change in serum bilirubin
timeFrame: 3 months
measure: Mean change in serum parathyroid hormone
timeFrame: 3 months
measure: Mean change in serum P1NP
timeFrame: 3 months
measure: Mean change in serum C-telopeptides
timeFrame: 3 months
measure: Mean change in musculoskeletal pain scores
timeFrame: 3 months
measure: Mean change in quality of life scores
timeFrame: 3 months
measure: Sickle cell disease-related complications
timeFrame: 3 months
measure: Participant recruitment
timeFrame: 3 months
measure: Participant retention
timeFrame: 3 months
measure: Participant compliance
timeFrame: 3 months
Locations:
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
Study officials:
affiliation: St. Justine's Hospital
name: Genevieve Mailhot, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Soe HHK, Abas AB, Than NN, Ni H, Singh J, Said ARBM, Osunkwo I. Vitamin D supplementation for sickle cell disease. Cochrane Database Syst Rev. 2020 May 28;5(5):CD010858. doi: 10.1002/14651858.CD010858.pub3.