Vitamin D Supplementation in Children With Sickle Cell Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Vitamin D bolus

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).

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; Placebo identical in taste and appearance to the vitamin D bolus
Experimental: Vitamin D bolus; 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; One single oral liquid vitamin D3 supplement of 300 000 IU; Other Names: Cholecalciferol

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypercalciuria	Number of patients with urinary calcium to creatinine ratio above normal reference range for age	7 days post-intervention
Hypercalcemia	Number of patients with serum calcium above normal reference range for age	3 months
Serum 25-hydroxyvitamin D levels	Number of patients with serum 25-hydroxyvitamin D levels >250 nmol/L	3 months
Mean change in weight	Group difference in the mean change of weight (kg) from baseline to 3 months.	3 months
Mean change in height	Group difference in the mean change of height (kg) from baseline to 3 months.	3 months
Mean change in hemoglobin	Group difference in the mean change of circulating hemoglobin from baseline to 3 months.	3 months
Mean change in fetal hemoglobin	Group difference in the mean change of circulating fetal hemoglobin from baseline to 3 months.	3 months
Mean change in leucocyte counts	Group difference in the mean change of blood leucocyte counts from baseline to 3 months.	3 months
Mean change in platelet counts	Group difference in the mean change of blood platelet counts from baseline to 3 months.	3 months
Mean change in reticulocyte counts	Group difference in the mean change of blood reticulocyte counts from baseline to 3 months	3 months
Mean change in neutrophil counts	Group difference in the mean change of blood neutrophil counts from baseline to 3 months	3 months
Mean change in mean corpuscular volume	Group difference in the mean change of blood mean corpuscular volume from baseline to 3 months	3 months
Mean change in serum creatinine	Group difference in the mean change of serum creatinine from baseline to 3 months.	3 months
Mean change in serum bilirubin	Group difference in mean change of serum bilirubin from baseline to 3 months.	3 months
Mean change in serum parathyroid hormone	Group difference in mean change of serum parathyroid hormone from baseline to 3 months	3 months
Mean change in serum P1NP	Group difference in mean change of serum amino-terminal propeptide of type I collagen (P1NP) from baseline to 3 months	3 months
Mean change in serum C-telopeptides	Group difference in mean change of serum C-telopeptides from baseline to 3 months	3 months
Mean change in musculoskeletal pain scores	Musculoskeletal pain will be assessed with the Brief Pain Inventory (BPI). Group difference in the mean change in BPI scores.	3 months
Mean change in quality of life scores	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.	3 months
Sickle cell disease-related complications	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	3 months
Participant recruitment	Percentage of patients recruited from those screened	3 months
Participant retention	Percentage of patients retained for the entire study duration	3 months
Participant compliance	Percentage of patients who comply with the study protocol	3 months

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Collaborators: Euro-Pharm
• Investigators: Principal Investigator: Genevieve Mailhot, PhD, St. Justine's Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2018
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): September 30, 2019

Study Registration Dates

• First Submitted: January 11, 2018
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): January 31, 2018

Study Record Updates

• Last Update Posted (Actual): March 23, 2020
• Last Update Submitted That Met QC Criteria: March 19, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Vitamin D; Bolus supplementation; Pilot randomised controlled trial
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: ND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No