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

This study has been completed.
Sponsor:
Collaborators:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00349726
First received: July 6, 2006
Last updated: January 9, 2011
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Infant, Newborn
Infant, Low Birth Weight
Infant, Small for Gestational Age
Infant, Premature
Retinopathy of Prematurity
Bronchopulmonary Dysplasia
Drug: Inositol lower volume
Drug: Inositol higher volume
Drug: Placebo lower volume
Drug: Placebo higher volume
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Population pharmacokinetics [ Time Frame: 0-100 hours following infusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Adverse events during and following infusion, using a neonatal toxicity classification [ Time Frame: Until discharge ] [ Designated as safety issue: Yes ]

Enrollment: 74
Study Start Date: June 2006
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   up to 6 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00349726

Locations
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, Indiana
Indiana University
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
RTI International
Durham, North Carolina, United States, 27705
Duke University
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
Sponsors and Collaborators
Investigators
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 Cincinnati Children's Medical Center
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
  More Information

Additional Information:
No publications provided

Responsible Party: Dale L. Phelps, Lead Principal Investigator, University of Rochester, NICHD Neonatal Research Network
ClinicalTrials.gov Identifier: NCT00349726     History of Changes
Other Study ID Numbers: NICHD-NRN-0036-1, U10HD021364, U10HD021373, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880, U10HD027904, U10HD034216, U10HD036790, U10HD040492, U10HD040689, U10HD053089, U10HD053109, U10HD053119, U10HD053124, UL1RR024139, UL1RR025744, UL1RR024979
Study First Received: July 6, 2006
Last Updated: January 9, 2011
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD Neonatal Research Network
Pharmacokinetics
Inositol
Very Low Birth Weight (VLBW)
Extremely Low Birth Weight (ELBW)
Prematurity

Additional relevant MeSH terms:
Birth Weight
Bronchopulmonary Dysplasia
Retinopathy of Prematurity
Body Weight
Eye Diseases
Infant, Newborn, Diseases
Infant, Premature, Diseases
Lung Diseases
Lung Injury
Respiratory Tract Diseases
Retinal Diseases
Signs and Symptoms
Ventilator-Induced Lung Injury
Inositol
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on October 20, 2014