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

Primary Purpose

Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Inositol lower volume
Inositol higher volume
Placebo lower volume
Placebo higher volume
Sponsored by
NICHD Neonatal Research Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infant, Newborn focused on measuring NICHD Neonatal Research Network, Pharmacokinetics, Inositol, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity

Eligibility Criteria

3 Days - 6 Days (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Yale University
  • Indiana University
  • Wayne State University
  • University of New Mexico
  • University of Rochester
  • RTI International
  • Duke University
  • Case Western Reserve University, Rainbow Babies and Children's Hospital
  • Brown University, Women & Infants Hospital of Rhode Island
  • University of Texas Southwestern Medical Center at Dallas
  • University of Utah

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

Inositol low volume

Inositol high volume

Placebo low volume

Placebo high volume

Arm Description

Single dose of intravenous inositol 5%, 60 mg/kg (1.2ml/kg) given over 20 minutes

Single dose of intravenous inositol 5%, 120 mg/kg (2.4ml/kg) given over 20 minutes

Placebo (5% glucose) at a volume equal to 60 mg/kg (1.2 ml/kg) given via IV over 20 minutes.

Placebo (5% glucose) at a volume equal to 120 mg/kg (2.4 ml/kg) given via IV over 20 minutes

Outcomes

Primary Outcome Measures

Population pharmacokinetics

Secondary Outcome Measures

Adverse events during and following infusion, using a neonatal toxicity classification

Full Information

First Posted
July 6, 2006
Last Updated
June 19, 2017
Sponsor
NICHD Neonatal Research Network
Collaborators
National Eye Institute (NEI), National Center for Research Resources (NCRR), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT00349726
Brief Title
Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants
Acronym
INS-1
Official Title
Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
June 2006 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NICHD Neonatal Research Network
Collaborators
National Eye Institute (NEI), National Center for Research Resources (NCRR), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Retinopathy of Prematurity, Bronchopulmonary Dysplasia (BPD)
Keywords
NICHD Neonatal Research Network, Pharmacokinetics, Inositol, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Inositol low volume
Arm Type
Experimental
Arm Description
Single dose of intravenous inositol 5%, 60 mg/kg (1.2ml/kg) given over 20 minutes
Arm Title
Inositol high volume
Arm Type
Experimental
Arm Description
Single dose of intravenous inositol 5%, 120 mg/kg (2.4ml/kg) given over 20 minutes
Arm Title
Placebo low volume
Arm Type
Placebo Comparator
Arm Description
Placebo (5% glucose) at a volume equal to 60 mg/kg (1.2 ml/kg) given via IV over 20 minutes.
Arm Title
Placebo high volume
Arm Type
Placebo Comparator
Arm Description
Placebo (5% glucose) at a volume equal to 120 mg/kg (2.4 ml/kg) given via IV over 20 minutes
Intervention Type
Drug
Intervention Name(s)
Inositol lower volume
Intervention Description
60 mg/kg (1.2ml/kg) of myo-inositol 5% given intravenously over 20 minutes.
Intervention Type
Drug
Intervention Name(s)
Inositol higher volume
Intervention Description
120 mg/kg (2.4ml/kg) of myo-inositol 5% given intravenously over 20 minutes.
Intervention Type
Drug
Intervention Name(s)
Placebo lower volume
Intervention Description
60 mg/kg (1.2ml/kg) of glucose 5% given intravenously over 20 minutes.
Intervention Type
Drug
Intervention Name(s)
Placebo higher volume
Intervention Description
120 mg/kg (2.4ml/kg) of glucose 5% given intravenously over 20 minutes.
Primary Outcome Measure Information:
Title
Population pharmacokinetics
Time Frame
0-100 hours following infusion
Secondary Outcome Measure Information:
Title
Adverse events during and following infusion, using a neonatal toxicity classification
Time Frame
Until discharge

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Days
Maximum Age & Unit of Time
6 Days
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abbot R. Laptook, MD
Organizational Affiliation
Brown University, Women & Infants Hospital of Rhode Island
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michele C. Walsh, MD MS
Organizational Affiliation
Case Western Reserve University, Rainbow Babies and Children's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ronald N. Goldberg, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Brenda B. Poindexter, MD MS
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Abhik Das, PhD
Organizational Affiliation
RTI International
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kristi L. Watterberg, MD
Organizational Affiliation
University of New Mexico
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dale L. Phelps, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pablo J. Sanchez, MD
Organizational Affiliation
University of Texas, Southwestern Medical Center at Dallas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Seetha Shankaran, MD
Organizational Affiliation
Wayne State University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Richard A. Ehrenkranz, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Roger G. Faix, MD
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Barbara J. Stoll, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kurt Schibler, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Krisa P. Van Meurs, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Waldemar A. Carlo, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kathleen A. Kennedy, MD MPH
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ivan D. Frantz, III, MD
Organizational Affiliation
Tufts Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06504
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
RTI International
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Case Western Reserve University, Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Brown University, Women & Infants Hospital of Rhode Island
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
University of Texas Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States

12. IPD Sharing Statement

Links:
URL
https://neonatal.rti.org/
Description
NICHD Neonatal Research Network

Learn more about this trial

Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants

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