Clinical trial NCT00349726: Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants
Official title: Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: National Eye Institute (NEI)
name: National Center for Research Resources (NCRR)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2006-07-10
Enrollment: 74
Sex: ALL
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Population pharmacokinetics
timeFrame: 0-100 hours following infusion
Secondary outcomes:
measure: Adverse events during and following infusion, using a neonatal toxicity classification
timeFrame: Until discharge
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University, Rainbow Babies and Children's Hospital
state: Ohio
city: Providence
country: United States
facility: Brown University, Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Brown University, Women & Infants Hospital of Rhode Island
name: Abbot R. Laptook, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University, Rainbow Babies and Children's Hospital
name: Michele C. Walsh, MD MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Ronald N. Goldberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: Brenda B. Poindexter, MD MS
role: PRINCIPAL_INVESTIGATOR
affiliation: RTI International
name: Abhik Das, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of New Mexico
name: Kristi L. Watterberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Dale L. Phelps, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas, Southwestern Medical Center at Dallas
name: Pablo J. Sanchez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Seetha Shankaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Richard A. Ehrenkranz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Roger G. Faix, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Barbara J. Stoll, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Kurt Schibler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Krisa P. Van Meurs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Waldemar A. Carlo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas Health Science Center, Houston
name: Kathleen A. Kennedy, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Tufts Medical Center
name: Ivan D. Frantz, III, MD
role: PRINCIPAL_INVESTIGATOR
References: