A Trial on Different Dosages of Vitamin D in Preterm Infants With Late-onset Sepsis

Effect of Different Dosages Oral Vitamin D on Serum Interleukin-6 in Preterm Infants With Late-onset Sepsis

This is a randomized controlled trial (RCT) to evaluate the influence of different doses of vitamin D3 (800 IU/d versus 400 IU/d), on serum levels of interleukin (IL)-6, TNF-alpha and C- reactive (CRP) in premature infants with clinical evidence of late-onset sepsis and to assess its influence on clinical outcomes of these infants.

Study Overview

• Status: Completed
• Conditions: Prematurity; Late-onset Sepsis
• Intervention / Treatment: Drug: High-dose vitamin D 3; Drug: Conventional-Dose Vitamin D 3

Detailed Description

Vitamin D has an important role in the regulation of both the innate and adaptive immune systems. There are very few studies of such roles in the neonatal population. It is potentially an attractive therapeutic agent for sepsis given its low cost and low risk of toxicity and side effects. There is no consensus regarding to the dose of vitamin D supplementation required for preterm infants given the paucity of evidence. AAP and ESPGHAN have recommended different dosages of vitamin D ranging from 400 IU to 1000 IU per day. The influence of different doses of vitamin D on immunological status and clinical outcomes of preterm infants with late-onset sepsis has not been evaluated before. This RCT will evaluate the influence of different doses of vitamin D3 (800 IU/d versus 400 IU/d), on serum levels of interleukin (IL)-6, TNF-alpha and C- reactive (CRP) in premature infants with clinical evidence of late-onset sepsis we will also evaluate their safety and influence on clinical outcomes of these infants

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Dakahlia
    • Mansoura, Dakahlia, Egypt, 35516
      • Neonatal Intensive Care Unit, Mansoura University Children Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 days to 4 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Preterm Infants (28-37 wk gestational age)

• Late-onset sepsis defined as clinical signs suggestive of infection after 72 h of birth. Clinical sepsis will be defined as the presence of three or more of the following categories of clinical signs:

  1. Temperature instability (hypothermia, hyperthermia);
  2. Respiratory (grunting, intercoastal retraction, apnea, tachypnea, cyanosis);
  3. Neurologic (hypotonia, lethargy, seizures);
  4. Gastrointestinal (feeding intolerance, abdominal distension).

Exclusion Criteria:

• Major congenital anomalies.
• Chromosomal anomalies.
• Known inborn error(s) of metabolism

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-dose vitamin D; Will receive oral cholecalciferol (vitamin D3) in a single daily dose of 800 IU from the time of diagnosis of sepsis until discharge from the NICU	Drug: High-dose vitamin D 3; Will receive oral cholecalciferol (vitamin D3) in a single daily dose of 800 IU from the time of diagnosis of sepsis until discharge from the NICU; Other Names: High-dose cholecalciferol
Active Comparator: Conventional-dose vitamin D; Will receive oral cholecalciferol (vitamin D3) in a single daily dose of 400 IU from the time of diagnosis of sepsis until discharge from the NICU	Drug: Conventional-Dose Vitamin D 3; Will receive oral cholecalciferol (vitamin D3) in a single daily dose of 400 IU from the time of diagnosis of sepsis until discharge from the NICU; Other Names: Conventional-dose cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum interleukin-6	Serum levels of interleukin-6 (IL-6) will be evaluated at enrollment and 7 days after daily vitamin D supplementation therapy. IL-6 concentrations will be determined by Endogenous Interleukin-ELISA	At trial entry and 7 days after daily vitamin D supplementation therapy
Serum tumor necrosis-alpha	Serum levels of tumor necrosis-alpha (TNF-alpha) will be evaluated at enrollment and 7 days after daily vitamin D supplementation therapy	At trial entry and 7 days after daily vitamin D supplementation therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum C-reactive protein (CRP)	Serum CRP will be evaluated at enrollment and 7 days	At trial entery and 7 days after daily vitamin D supplementation therapy
Serum 25(OH)D levels	Serum 25(OH)D levels will be measured by ELISA at trial entry, at day 7 and at 40 weeks postmenstrual age	at trial entry, 7 days after daily vitamin D supplementation therapy and at 40 weeks postmenstrual age
Serum calcium, phosphorus and urinary calcium	Participants will be followed for the duration of hospital stay, serum calcium, phosphorus and urinary calcium well be assessed every week for an expected average of 5 weeks	Participants will be followed for the duration of hospital stay, serum calcium, phosphorus and urinary calcium well be assessed every week for an expected average of 5 weeks
Abdominal ultrasonography	Abdominal ultrasonography to detect any nephrocalcinosis will be done at 40 weeks postmenstrual age	40 weeks postmenstrual age
Mortality	In-hospital mortality during NICU admission for an expected average of 5 weeks	Baseline
Neonatal morbidities	Participants will be followed for the duration of hospital stay, for an expected average of 5 weeks and the incidence of neonatal morbidities e.g. NEC, retinopathy of prematurity, disseminated intravascular coagulopathy and renal dysfunction will be assessed	Participants will be followed for the duration of hospital stay, for an expected average of 4 weeks

Collaborators and Investigators

• Sponsor: Mansoura University Children Hospital

Publications and helpful links

General Publications

• Huey SL, Acharya N, Silver A, Sheni R, Yu EA, Pena-Rosas JP, Mehta S. Effects of oral vitamin D supplementation on linear growth and other health outcomes among children under five years of age. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD012875. doi: 10.1002/14651858.CD012875.pub2.
• Abrams SA; Committee on Nutrition. Calcium and vitamin d requirements of enterally fed preterm infants. Pediatrics. 2013 May;131(5):e1676-83. doi: 10.1542/peds.2013-0420. Epub 2013 Apr 29.
• Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T, Domellof M, Embleton ND, Fusch C, Genzel-Boroviczeny O, Goulet O, Kalhan SC, Kolacek S, Koletzko B, Lapillonne A, Mihatsch W, Moreno L, Neu J, Poindexter B, Puntis J, Putet G, Rigo J, Riskin A, Salle B, Sauer P, Shamir R, Szajewska H, Thureen P, Turck D, van Goudoever JB, Ziegler EE; ESPGHAN Committee on Nutrition. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2010 Jan;50(1):85-91. doi: 10.1097/MPG.0b013e3181adaee0.
• Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am. 2010 Jun;39(2):365-79, table of contents. doi: 10.1016/j.ecl.2010.02.010.
• Moromizato T, Litonjua AA, Braun AB, Gibbons FK, Giovannucci E, Christopher KB. Association of low serum 25-hydroxyvitamin D levels and sepsis in the critically ill. Crit Care Med. 2014 Jan;42(1):97-107. doi: 10.1097/CCM.0b013e31829eb7af.
• Kim SY. The pleiomorphic actions of vitamin D and its importance for children. Ann Pediatr Endocrinol Metab. 2013 Jun;18(2):45-54. doi: 10.6065/apem.2013.18.2.45. Epub 2013 Jun 30.
• Abdel-Hady H, Yahia S, Megahed A, Mosbah A, Seif B, Nageh E, Bhattacharjee I, Aly H. Mediators in Preterm Infants With Late-onset Sepsis: A Randomized Controlled Trial. J Pediatr Gastroenterol Nutr. 2019 Apr;68(4):578-584. doi: 10.1097/MPG.0000000000002238.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: October 20, 2014
• First Submitted That Met QC Criteria: October 23, 2014
• First Posted (Estimate): October 24, 2014

Study Record Updates

• Last Update Posted (Estimate): September 30, 2015
• Last Update Submitted That Met QC Criteria: September 29, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Vitamin D; Preterm; Interleukin-6; Dose; Tumor necrosis factor-alpha; late-onset sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: MS 306