ViDES Trial (Vitamin D Extra Supplementation)

Randomized Trial of Enteral Vitamin D Supplementation in Infants < 28 Weeks Gestational Age or <1000 Grams Birth Weight

The objective of the study is to compare supplementation with vitamin D at 800 IU/day to usual care for the first 28 days after birth with respect to 25 (OH) vitamin D levels and indicators of likely or plausible effects of vitamin D supplementation on the function or structure of the lung, bones, immune system, and brain in extremely premature (EP) infants who are <28 weeks gestational age (GA) or <1000 grams of birth weight (BW). The study results will be analyzed as intention to treat Bayesian analyses (Frequentist analyses will also be performed).

Study Overview

• Status: Recruiting
• Conditions: Vitamin D Deficiency
• Intervention / Treatment: Dietary supplement: Placebo; Other: Usual Care; Dietary supplement: 800 IU/day vitamin D supplementation with feedings in the first 28 days after birth

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria del Mar Romero López, MD; Phone Number: 713-500-7283; Email: Maria.del.Mar.RomeroLopez@uth.tmc.edu
• Study Contact Backup: Name: Emily K Stephens, BSN, RNC-NIC; Phone Number: (713) 500-5734; Email: Emily.K.Stephens@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77006
      • Recruiting
      • The University of Texas Health Science Center at Houston
      • Contact: Maria del Mar Romero López, MD; Phone Number: 713-500-7283; Email: Maria.del.Mar.RomeroLopez@uth.tmc.edu
      • Contact: Emily Stephens, BSN, RNC-NIC; Phone Number: (713) 500-5734; Email: Emily.K.Stephens@uth.tmc.edu
      • Sub-Investigator: Matthew Rysavy, MD, PhD
      • Sub-Investigator: Amir Khan, MD
      • Sub-Investigator: Jon Tyson, MD, MPH
      • Sub-Investigator: Claudia Pedroza, PhD
      • Sub-Investigator: Mamta Naik, RD, PharmD, BCPPS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 4 days (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants born at < 28 weeks gestational age (GA) or <1000 grams birth weight (BW)
• Inborn
• Informed written consent in an Institutional Review Board (IRB)-approved manner

Exclusion Criteria:

• GA >32 weeks regardless of birth weight (BW)
• Any major congenital anomaly
• A known congenital nonbacterial infection
• Prenatal diagnosis of disorders that affect vitamin D absorption (e.g, cystic fibrosis)
• Such severe illness or immaturity that the attending neonatologist judges intensive care to be unjustified.

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
Active Comparator: Usual care plus placebo; Infants will receive placebo (normal saline) in the first 28 days after birth. Care will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices. When the infant receives about 120 to 160 mL/kg/day of fortified milk at 24 kcal/ounce, the infant will receive supplementation with 400 IU/day of vitamin D as usual care.	Dietary supplement: Placebo; Placebo is normal saline, given in the first 28 days after birth, prepared to have the same volume and appearance as vitamin D, which is a clear odorless solution.; Other Names: Normal saline; Other: Usual Care; Care will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices. When the infant receives about 120 to 160 mL/kg/day of fortified milk at 24 kcal/ounce, the infant will receive supplementation with 400 IU/day of vitamin D as usual care.
Experimental: Usual care plus vitamin D supplementation; Infants will receive cholecalciferol 800 IU/day in the first 28 days after birth, given enterally four times per day (0.5mL per dose = 200 IU) until the infant is provided 400 IU/day (when feedings reach about 120 -160 mL/kg/day). At that point the study cholecalciferol will be reduced to 400 IU/day for a total supplementation of 800 IU/day.	Other: Usual Care; Care will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices. When the infant receives about 120 to 160 mL/kg/day of fortified milk at 24 kcal/ounce, the infant will receive supplementation with 400 IU/day of vitamin D as usual care.; Dietary supplement: 800 IU/day vitamin D supplementation with feedings in the first 28 days after birth; 800 IU/day Vitamin D supplementation until 400 IU/day are provided as part of usual care (started when infants receive full feedings of about 120-160 mL/kg/day). At that point the intervention becomes a supplement of 400 IU/day above that given with usual care. In this way all infants in the intervention group receive 800 IU/day of vitamin D total supplementation in the first 28 days after birth with feedings.; Other Names: Cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
25-hydroxyvitamin D (25[OH]D) level	about 28 days after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
25-hydroxyvitamin D (25[OH]D) level		36 weeks after birth
Type of respiratory support required at 36 weeks postmenstrual age	Data will be reported categorically as: Number of participants who survive without respiratory support; Number of participants who survive with nasal cannula at ≤ 2 liters (L)/minute; Number of participants who survive with nasal cannula >2 L/minute or noninvasive positive airway pressure; Number of participants who survive with invasive mechanical ventilation; Number of participants who die	36 weeks postmenstrual age (or at the time of discharge home if earlier)
Length of Hospital stay		from time of birth to time of discharge (about 0 to 60 weeks after birth)
Number of participants who are still on respiratory support	Respiratory support includes supplemental oxygen and positive pressure ventilation.	22 to 26 months corrected age
Number of days of supplemental oxygen		from time of birth to time of discharge (about 0 to 60 weeks after birth)
Number of days of mechanical ventilation		from time of birth to time of discharge (about 0 to 60 weeks after birth)
Number of days of positive pressure support		from time of birth to time of discharge (about 0 to 60 weeks after birth)
Number of participants who receive steroid treatment to decrease respiratory support		from baseline to 36 weeks postmenstrual age
Number of participants with pulmonary hypertension		36 weeks postmenstrual age
Number of participants with wheezing		2 years
Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator	Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.	28 days of life
Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator	Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.	36 weeks postmenstrual age
Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator	Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.	2 years
Length as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator	Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.	28 days of life
Length as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator	Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.	36 weeks postmenstrual age
Length as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator	Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.	2 years
Head circumference as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator	Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.	28 days of life
Head circumference as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator	Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.	36 weeks postmenstrual age
Head circumference as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator	Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.	2 years
Number of participants with any fractures		from baseline to 36 weeks postmenstrual age
Number of participants with hospital-acquired sepsis		from day 3 after birth to the time of discharge (which is 0 to 60 weeks after birth)
Calcium level		0 to 36 weeks postmenstrual age
Phosphorus level		0 to 36 weeks postmenstrual age
Alkaline phosphatase level		0 to 36 weeks postmenstrual age
Neurodevelopment as assessed by the Bayley-IV Scales of Infant and Toddler Development	Score ranges from 40 to 160, with a higher score indicating a better outcome.	2 years
Number of participants with neurodevelopmental impairment (NDI)		2 years
Number of participants who die or have a morbidity	Morbidities include retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), neurodevelopmental impairment (NDI), necrotizing enterocolitis (NEC), and patent ductus arteriosus (PDA).	36 weeks postmenstrual age
Vitamin D status as indicated by serum concentration of 24,25(OH)2D3 as assessed by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS)		about 28 days after birth
Vitamin D status as indicated by serum concentration of 24,25(OH)2D3 as assessed by LC-MS/MS		36 weeks postmenstrual age
Vitamin D status as indicated by serum concentration of 3-epi-25(OH)D3 as assessed by LC-MS/MS		about 28 days after birth
Vitamin D status as indicated by serum concentration of 3-epi-25(OH)D3 as assessed by LC-MS/MS		36 weeks postmenstrual age
Vitamin D status as indicated by serum concentration of 25(OH)D3 as assessed by LC-MS/MS		about 28 days after birth
Vitamin D status as indicated by serum concentration of 25(OH)D3 as assessed by LC-MS/MS		36 weeks postmenstrual age

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Center for Advancing Translational Sciences (NCATS); The Gerber Foundation
• Investigators: Principal Investigator: Maria del Mar Romero López, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2022
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 11, 2022
• First Submitted That Met QC Criteria: July 11, 2022
• First Posted (Actual): July 14, 2022

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Vitamin D; Premature infant
• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: HSC-MS-22-0563; KL2TR003168 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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