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Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants (INS-1)

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ClinicalTrials.gov Identifier: NCT00349726
Recruitment Status : Completed
First Posted : July 10, 2006
Last Update Posted : June 20, 2017
Sponsor:
Collaborators:
National Eye Institute (NEI)
National Center for Research Resources (NCRR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
NICHD Neonatal Research Network

Tracking Information
First Submitted Date  ICMJE July 6, 2006
First Posted Date  ICMJE July 10, 2006
Last Update Posted Date June 20, 2017
Study Start Date  ICMJE June 2006
Actual Primary Completion Date December 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2008)
Population pharmacokinetics [ Time Frame: 0-100 hours following infusion ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 6, 2006)
Population pharmacokinetics
Change History Complete list of historical versions of study NCT00349726 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2008)
Adverse events during and following infusion, using a neonatal toxicity classification [ Time Frame: Until discharge ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2006)
Adverse events
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants
Official Title  ICMJE Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants
Brief Summary This pilot study was a randomized, placebo-controlled, clinical trial to measure changes in blood and urine levels of inositol in premature infants at high risk for retinopathy of prematurity (ROP) following a single intravenous dose of inositol. Based on previous studies, the premise is that maintaining inositol concentrations similar to those occurring naturally in utero will reduce the rates of ROP and bronchopulmonary dysplasia in premature infants. The objective was to evaluate the single-dose pharmacokinetics and safety of different amounts of intravenous myo-inositol (provided by Ross Products Division, Abbott Laboratories) in very low birth weight neonates, in preparation for a future Phase III multi-center randomized controlled trial. This study enrolled 74 infants at high risk for retinopathy at 9 NICHD Neonatal Research Network sites, and randomly assigned them to receive either 60mg/kg of 5% inositol, 120 mg/kg of 5% inositol, 60 mg/kg of 5% glucose (the placebo), or 120 mg/kg of 5% glucose.
Detailed Description

Retinopathy of prematurity (ROP) is an abnormal growth of the blood vessels in the eye that occurs primarily in very premature infants. Eye development occurs normally in the womb; in infants born prematurely, however, the blood vessels must finish developing outside the protective environment of the uterus. Retinopathy of prematurity (also known as retrolental fibroplasia) is a leading cause of blindness and other vision impairments (myopia, strabismus, and amblyopia) in children, both in developed and developing countries.

Inositol is a naturally-occurring sugar alcohol produced by the placenta and is present in high levels in fetal blood throughout pregnancy in humans and other animals. Serum levels fall rapidly after birth, although this fall is moderated in infants who receive breast milk. Two randomized trials have shown that intravenous inositol supplementation in the first week significantly reduced death, bronchopulmonary dysplasia (BPD), and retinopathy. One study of oral supplements was less convincing, but also supported reduction of retinopathy.

This pilot study evaluated the half-life pharmacokinetics of a single-dose of myo-inositol (provided by Ross Products Division, Abbott Laboratories) in very low birth weight infants, looking at changes in blood and urine inositol levels. The premise is that maintaining inositol concentrations similar to those occurring naturally in utero will reduce the rates of retinopathy and bronchopulmonary dysplasia in premature infants. Results from this study will be used to select the doses for a subsequent multi-dose pilot study, and for the planned large multi-center trials.

In this study, nine NICHD Neonatal Research Network sites enrolled 74 infants of less than 30 weeks gestation and randomly assigned them to receive either 60mg/kg of 5% inositol, 120 mg/kg of 5% inositol, 60 mg/kg of 5% glucose (the placebo), or 120 mg/kg of 5% glucose. Concentrations of inositol were measured in both blood and urine to determine population pharmacokinetic parameters for these infants.

Stratification: Enrolled infants were stratified by age with 37 infants of 23 0/7 to 26 6/7 weeks in one group and 37 infants of 27 0/7 to 29 6/7 weeks in a second group.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Infant, Newborn
  • Infant, Low Birth Weight
  • Infant, Small for Gestational Age
  • Infant, Premature
  • Retinopathy of Prematurity
  • Bronchopulmonary Dysplasia (BPD)
Intervention  ICMJE
  • Drug: Inositol lower volume
    60 mg/kg (1.2ml/kg) of myo-inositol 5% given intravenously over 20 minutes.
  • Drug: Inositol higher volume
    120 mg/kg (2.4ml/kg) of myo-inositol 5% given intravenously over 20 minutes.
  • Drug: Placebo lower volume
    60 mg/kg (1.2ml/kg) of glucose 5% given intravenously over 20 minutes.
  • Drug: Placebo higher volume
    120 mg/kg (2.4ml/kg) of glucose 5% given intravenously over 20 minutes.
Study Arms  ICMJE
  • Experimental: Inositol low volume
    Single dose of intravenous inositol 5%, 60 mg/kg (1.2ml/kg) given over 20 minutes
    Intervention: Drug: Inositol lower volume
  • Experimental: Inositol high volume
    Single dose of intravenous inositol 5%, 120 mg/kg (2.4ml/kg) given over 20 minutes
    Intervention: Drug: Inositol higher volume
  • Placebo Comparator: Placebo low volume
    Placebo (5% glucose) at a volume equal to 60 mg/kg (1.2 ml/kg) given via IV over 20 minutes.
    Intervention: Drug: Placebo lower volume
  • Placebo Comparator: Placebo high volume
    Placebo (5% glucose) at a volume equal to 120 mg/kg (2.4 ml/kg) given via IV over 20 minutes
    Intervention: Drug: Placebo higher volume
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 20, 2008)
74
Original Enrollment  ICMJE
 (submitted: July 6, 2006)
72
Actual Study Completion Date  ICMJE December 2007
Actual Primary Completion Date December 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 23 0/7 to 26 6/7 weeks gestational age (36 infants) or
  • 27 0/7 to 29 6/7 weeks gestational age (36 infants)
  • 600-1500 grams birth weight
  • No enteral feedings since birth at enrollment
  • 3-6 days (25-132 hours) postnatal age

Note: Because of the high mortality expected in this population (15-20%), the study design (originally for 72 infants) required recruitment of a replacement subject if any infant failed to complete the four blood samples during the first week of the study.

Exclusion Criteria:

  • Major congenital anomalies
  • Moribund or not to be provided continued support
  • Renal failure suspected (creatinine >2.5 with oliguria)
  • Exchange transfusion received or expected to receive
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 6 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00349726
Other Study ID Numbers  ICMJE NICHD-NRN-0036-1
U10HD021364 ( U.S. NIH Grant/Contract )
U10HD021373 ( U.S. NIH Grant/Contract )
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD027851 ( U.S. NIH Grant/Contract )
U10HD027853 ( U.S. NIH Grant/Contract )
U10HD027856 ( U.S. NIH Grant/Contract )
U10HD027871 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
U10HD027904 ( U.S. NIH Grant/Contract )
U10HD034216 ( U.S. NIH Grant/Contract )
U10HD036790 ( U.S. NIH Grant/Contract )
U10HD040492 ( U.S. NIH Grant/Contract )
U10HD040689 ( U.S. NIH Grant/Contract )
U10HD053089 ( U.S. NIH Grant/Contract )
U10HD053109 ( U.S. NIH Grant/Contract )
U10HD053119 ( U.S. NIH Grant/Contract )
U10HD053124 ( U.S. NIH Grant/Contract )
UL1RR024139 ( U.S. NIH Grant/Contract )
UL1RR025744 ( U.S. NIH Grant/Contract )
UL1RR024979 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NICHD Neonatal Research Network
Study Sponsor  ICMJE NICHD Neonatal Research Network
Collaborators  ICMJE
  • National Eye Institute (NEI)
  • National Center for Research Resources (NCRR)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Principal Investigator: Abbot R. Laptook, MD Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator: Michele C. Walsh, MD MS Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator: Ronald N. Goldberg, MD Duke University
Principal Investigator: Brenda B. Poindexter, MD MS Indiana University
Principal Investigator: Abhik Das, PhD RTI International
Principal Investigator: Kristi L. Watterberg, MD University of New Mexico
Principal Investigator: Dale L. Phelps, MD University of Rochester
Principal Investigator: Pablo J. Sanchez, MD University of Texas, Southwestern Medical Center at Dallas
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
Principal Investigator: Roger G. Faix, MD University of Utah
Principal Investigator: Barbara J. Stoll, MD Emory University
Principal Investigator: Kurt Schibler, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Krisa P. Van Meurs, MD Stanford University
Principal Investigator: Waldemar A. Carlo, MD University of Alabama at Birmingham
Principal Investigator: Kathleen A. Kennedy, MD MPH The University of Texas Health Science Center, Houston
Principal Investigator: Ivan D. Frantz, III, MD Tufts Medical Center
PRS Account NICHD Neonatal Research Network
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP