Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants
Condition: Infant, Newborn; Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature; Retinopathy of Prematurity; Bronchopulmonary Dysplasia (BPD)
MeSH terms: Bronchopulmonary Dysplasia; Retinopathy of Prematurity; Premature Birth; Birth Weight
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Inositol lower volume; Inositol higher volume; Placebo lower volume; Placebo higher volume
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 60 mg/kg (1.2ml/kg) of myo-inositol 5% given intravenously over 20 minutes.; 120 mg/kg (2.4ml/kg) of myo-inositol 5% given intravenously over 20 minutes.; 60 mg/kg (1.2ml/kg) of glucose 5% given intravenously over 20 minutes.; 120 mg/kg (2.4ml/kg) of glucose 5% given intravenously over 20 minutes.
Intervention MeSH terms: Inositol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: NICHD Neonatal Research Network; Pharmacokinetics; Inositol; Very Low Birth Weight (VLBW); Extremely Low Birth Weight (ELBW); Prematurity