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

Abstract

<p id="d13974537e225"> <div class="list"> <a class="named-anchor" id="d13974537e227"> <!-- named anchor --> </a> <ul class="so-custom-list"> <li id="d13974537e228"> <div class="so-custom-list-content so-ol"> <p class="first" id="d13974537e229">Annual rates of respiratory illness in sickle cell disease decreased by &gt;50% during the second year of monthly doses of oral vitamin D ₃. </p> </div> </li> <li id="d13974537e234"> <div class="so-custom-list-content so-ol"> <p class="first" id="d13974537e235">Reduction in rates was similar with high-dose (100 000 IU/mo) and standard-dose (12 000 IU/mo) treatment. </p> </div> </li> </ul> </div> </p><p class="first" id="d13974537e239">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 ₃ 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 ₃ (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 ₃ was associated with a &gt;50% reduction in the rate of respiratory illness during the second year ( <i>P</i> = .0005), with similar decreases associated with high- and standard-dose treatment. This trial was registered at <a data-untrusted="" href="http://www.clinicaltrials.gov" id="d13974537e253" target="xrefwindow">www.clinicaltrials.gov</a> as #NCT01443728. </p><p id="d13974537e260"> <div class="fig panel" id="absf1"> <a class="named-anchor" id="absf1"> <!-- named anchor --> </a> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/b5a8ba3b-a472-485e-9a6b-742277212d39/PubMedCentral/image/advances013979absf1"/> </div> <div class="panel-content"/> </div> </p>