Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease

Abstract

In sickle cell disease, respiratory infection and asthma may lead to respiratory complications that are a leading cause of morbidity and mortality. Vitamin D has anti-infective and immunomodulatory effects that may decrease the risk for respiratory infections, asthma, and acute chest syndrome. We conducted a randomized double-blind active-controlled clinical trial to determine whether monthly oral vitamin D can reduce the rate of respiratory events in children with sickle cell disease. Seventy sickle cell subjects, ages 3-20 years, with baseline records of respiratory events over 1 year before randomization, underwent screening. Sixty-two subjects with 25-hydroxyvitamin D levels of 5-60 ng/mL were randomly assigned to oral vitamin D (100 000 IU or 12 000 IU, n = 31 each) under observed administration once monthly for 2 years. The primary outcome was the annual rate of respiratory events (respiratory infection, asthma exacerbation, or acute chest syndrome) ascertained by the use of a validated questionnaire administered biweekly. Analysis included 62 children (mean age of 9.9 years, 52% female, and predominantly with homozygous HbS disease [87%]) with mean baseline 25-hydroxyvitamin D of 14.3 ng/mL. The annual rates of respiratory events at baseline and intervention years 1 and 2 were 4.34 ± 0.35, 4.28 ± 0.36, and 1.49 ± 0.37 (high dose) and 3.91 ± 0.35, 3.34 ± 0.37, and 1.54 ± 0.37 (standard dose), respectively. In pediatric patients with sickle cell disease, 2-year monthly oral vitamin D was associated with a >50% reduction in the rate of respiratory illness during the second year ( = .0005), with similar decreases associated with high- and standard-dose treatment. This trial was registered at www.clinicaltrials.gov as #NCT01443728.

Vitamin D Supplementation Improves Health-Related Quality of Life and Physical Performance in Children with Sickle Cell Disease and in Healthy Children

“…For children with HbSS, vitamin supplementation improved their clinical status with increased fetal hemoglobin, decreased inflammatory status, and reduced platelet counts (Dougherty et al, 2015). A 2-year supplementation (monthly oral 100,000 or 12,000 IU) study improved annual rates of respiratory illness in children aged 3−20 years with SCD (reduction of > 50%; Lee et al, 2018). Although other vitamin D supplementation trials in SCD have been conducted, many have not been of sufficient size or quality to inform clinical practice.…”

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials

“…30 Since the date of the final literature search performed for that study (December 2015), fifteen RCTs with 19,569 participants fulfilling the same eligibility criteria have been completed and analysed. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] We therefore sought data from these more recent studies for inclusion in an updated metaanalysis of aggregate (trial-level) data to determine whether vitamin D reduced ARI risk overall, and to evaluate whether effects of vitamin D on ARI risk varied according to baseline 25(OH)D concentration and/or dosing regimen (frequency, dose size, and trial duration).…”

Vitamin D and Nonskeletal Complications among Egyptian Sickle Cell Disease Patients

“…Several studies conducted in children confirmed our findings of significant association between VDD and increased risk of viral and bacterial respiratory tract infections [ 37 – 39 ]; Urashima and colleagues even suggest that vitamin D supplementation plays a role in prevention of seasonal influenza [ 40 ]. Other authors encounter more than 50% reduction of the respiratory illness rate on the second year of monthly vitamin D supplementation [ 41 ].…”