Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants (INS-1)
|Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Retinopathy of Prematurity Bronchopulmonary Dysplasia (BPD)||Drug: Inositol lower volume Drug: Inositol higher volume Drug: Placebo lower volume Drug: Placebo higher volume||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants|
- Population pharmacokinetics [ Time Frame: 0-100 hours following infusion ]
- Adverse events during and following infusion, using a neonatal toxicity classification [ Time Frame: Until discharge ]
|Study Start Date:||June 2006|
|Study Completion Date:||December 2007|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
Experimental: Inositol low volume
Single dose of intravenous inositol 5%, 60 mg/kg (1.2ml/kg) given over 20 minutes
Drug: Inositol lower volume
60 mg/kg (1.2ml/kg) of myo-inositol 5% given intravenously over 20 minutes.
Experimental: Inositol high volume
Single dose of intravenous inositol 5%, 120 mg/kg (2.4ml/kg) given over 20 minutes
Drug: Inositol higher volume
120 mg/kg (2.4ml/kg) of myo-inositol 5% given intravenously over 20 minutes.
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.
Drug: Placebo lower volume
60 mg/kg (1.2ml/kg) of glucose 5% given intravenously over 20 minutes.
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
Drug: Placebo higher volume
120 mg/kg (2.4ml/kg) of glucose 5% given intravenously over 20 minutes.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00349726
|United States, Connecticut|
|New Haven, Connecticut, United States, 06504|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|United States, Michigan|
|Wayne State University|
|Detroit, Michigan, United States, 48201|
|United States, New Mexico|
|University of New Mexico|
|Albuquerque, New Mexico, United States, 87131|
|United States, New York|
|University of Rochester|
|Rochester, New York, United States, 14642|
|United States, North Carolina|
|Durham, North Carolina, United States, 27705|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Case Western Reserve University, Rainbow Babies and Children's Hospital|
|Cleveland, Ohio, United States, 44106|
|United States, Rhode Island|
|Brown University, Women & Infants Hospital of Rhode Island|
|Providence, Rhode Island, United States, 02905|
|United States, Texas|
|University of Texas Southwestern Medical Center at Dallas|
|Dallas, Texas, United States, 75235|
|United States, Utah|
|University of Utah|
|Salt Lake City, Utah, United States, 84108|
|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|