Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Multi-dose Pharmacokinetics and Dose Ranging of Inositol in Premature Infants (INS-2)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01030575
First received: December 10, 2009
Last updated: September 26, 2013
Last verified: January 2013

December 10, 2009
September 26, 2013
January 2010
May 2011   (final data collection date for primary outcome measure)
Population pharmacokinetics [ Time Frame: Until 10 weeks of age or hospital discharge ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01030575 on ClinicalTrials.gov Archive Site
Adverse events during and following infusion, using a neonatal toxicity classification [ Time Frame: Until hospital discharge ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Multi-dose Pharmacokinetics and Dose Ranging of Inositol in Premature Infants (INS-2)
Phase II Randomized, Double-Masked, Placebo-Controlled, Safety, Pharmacokinetic, and Dose-Ranging Study of Multiple Doses of Inositol in Premature Infants

This pilot study is 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 repeated doses 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 is to evaluate pharmacokinetics, safety, and clinical outcomes of multiple doses of three different dose amounts of myo-inositol (provided by Abbott Laboratories) in very low birth weight premature infants. This study will enroll an estimated 96 infants at 17 NICHD Neonatal Research Network sites. Infants will be randomly assigned to receive either 10 mg/kg of 5% inositol, 40 mg/kg of 5% inositol, 80 mg/kg of 5% inositol, or 5% glucose given in the same volumes and timings as the inositol dosage to maintain masking. Enrollees will receive their assigned dose or placebo daily, starting within 72 hours of birth, and continuing until they reach 34 weeks post-menstrual age, 10 weeks chronologic age, or until the time of hospital discharge, whichever occurs first. The study drug will be administered first intravenously; as the infants progress to full feeding, the drug will be given enterally (orally or via feeding tube). Enrollees will be seen for a follow-up examination at 18-22 months corrected age. This pilot study is in preparation for a future Phase III multi-center randomized controlled trial.

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 fetus and 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 or fortified formula. Two randomized trials have shown that intravenous inositol supplementation in the first week significantly reduced death, bronchopulmonary dysplasia (BPD), and retinopathy. One study of enteral supplements (given orally or via feeding tube) was less convincing, but also supported reduction of retinopathy.

This pilot study will evaluate changes in blood and urine inositol levels (half-life pharmacokinetics) of multiple doses of myo-inositol (provided by Abbott Laboratories, Abbott Nutrition Division) given to very low birth weight infants. 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 dose for a large multi-center trial.

In this study, 17 NICHD Neonatal Research Network sites will enroll approximately 96 infants at 12-72 hours of age. Enrolled infants will be randomly assigned to receive either 10mg/kg of 5% inositol, 40 mg/kg of 5% inositol, 80 mg/kg of 5% inositol, or 5% glucose given in the same volumes and timings as the inositol dosage to maintain masking. Inositol will be administered intravenously until babies are feeding normally, at which time the same dose and formulation will be administered enterally (orally or via feeding tube). Concentrations of inositol will be measured in blood, urine, and milk received.

Stratification: Recruitment will be stratified by gestational age into infants born at 23 0/7 to 26 6/7 weeks gestational age and infants born at 27 0/7 to 29 6/7 weeks gestational age.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Infant, Newborn
  • Infant, Low Birth Weight
  • Infant, Small for Gestational Age
  • Infant, Premature
  • Retinopathy of Prematurity
  • Bronchopulmonary Dysplasia (BPD)
  • Drug: Inositol lower volume
    5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
    Other Name: Myo-inositol 5%
  • Drug: Inositol mid-level volume
    20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
    Other Name: Myo-inositol 5%
  • Drug: Inositol high volume
    40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
    Other Name: Myo-inositol 5%
  • Drug: Placebo low volume
    Glucose 5% given in volumes equal to that of the comparator drug
    Other Name: Dextrose
  • Experimental: Inositol low volume
    10 mg/kg/day Intravenous inositol 5%
    Intervention: Drug: Inositol lower volume
  • Experimental: Inositol mid-level volume
    40 mg/kg/day Intravenous inositol 5%
    Intervention: Drug: Inositol mid-level volume
  • Experimental: Inositol high volume
    80 mg/kg/day Intravenous inositol 5%
    Intervention: Drug: Inositol high volume
  • Placebo Comparator: Placebo
    Glucose 5% given in volumes equal to that of the comparator drug
    Intervention: Drug: Placebo low volume
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
125
September 2013
May 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 23 0/7 to 26 6/7 weeks gestational age (48 infants) or
  • 27 0/7 to 29 6/7 weeks gestational age (48 infants)
  • 401 grams birth weight or larger
  • 12-72 hours of age

Exclusion Criteria:

  • Major congenital and intracranial anomalies
  • Moribund or not to be provided continued support
  • Seizures
  • Suspected renal failure (oliguria <0.6 cc/kg/hr for >24 hours or creatinine >2.5 mg/dL)
Both
up to 72 Hours
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01030575
NICHD-NRN-0036-2, U10HD021364, U10HD021373, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880, U10HD027904, U10HD034216, U10HD036790, U10HD040492, U10HD040689, U10HD053089, U10HD053109, U10HD053119, U10HD053124, UL1RR024139, UL1RR025744, UL1RR024979, M01RR008084
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • National Eye Institute (NEI)
  • National Center for Research Resources (NCRR)
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: Barbara J. Stoll, MD Emory University
Principal Investigator: Brenda B. Poindexter, MD MS Indiana University
Principal Investigator: Abhik Das, PhD RTI International
Principal Investigator: Krisa P. Van Meurs, MD Stanford University
Principal Investigator: Ivan D. Frantz III, MD Tufts Medical Center
Principal Investigator: Kurt Schibler, MD Cincinnati Children's Medical Center
Principal Investigator: Waldemar A. Carlo, MD University of Alabama at Birmingham
Principal Investigator: Edward F Bell, MD University of Iowa
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: Kathleen A. Kennedy, MD MPH The University of Texas Health Science Center, Houston
Principal Investigator: Roger G. Faix, MD University of Utah
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
January 2013

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