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
  Purpose

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.


Condition Intervention Phase
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 mid-level volume
Drug: Inositol high volume
Drug: Placebo low 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: Prevention
Official Title: Phase II Randomized, Double-Masked, Placebo-Controlled, Safety, Pharmacokinetic, and Dose-Ranging Study of Multiple Doses of Inositol in Premature 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: Until 10 weeks of age or hospital discharge ] [ Designated as safety issue: Yes ]

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

Enrollment: 125
Study Start Date: January 2010
Study Completion Date: September 2013
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inositol low volume
10 mg/kg/day Intravenous inositol 5%
Drug: Inositol lower volume
5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
Other Name: Myo-inositol 5%
Experimental: Inositol mid-level volume
40 mg/kg/day Intravenous 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%
Experimental: Inositol high volume
80 mg/kg/day Intravenous inositol 5%
Drug: Inositol high volume
40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
Other Name: Myo-inositol 5%
Placebo Comparator: Placebo
Glucose 5% given in volumes equal to that of the comparator drug
Drug: Placebo low volume
Glucose 5% given in volumes equal to that of the comparator drug
Other Name: Dextrose

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 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.

  Eligibility

Ages Eligible for Study:   up to 72 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  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: NCT01030575

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
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
Duke University
Durham, North Carolina, United States, 27710
RTI International
Durham, North Carolina, United States, 27705
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
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
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: 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
  More Information

Additional Information:
No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT01030575     History of Changes
Other Study ID Numbers: 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
Study First Received: December 10, 2009
Last Updated: September 26, 2013
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
Retinal Diseases
Retinopathy of Prematurity
Body Weight
Signs and Symptoms
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Eye Diseases
Inositol
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014