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



Status:Completed
Conditions:Bronchitis, Ocular, Women's Studies
Therapuetic Areas:Ophthalmology, Pulmonary / Respiratory Diseases, Reproductive
Healthy:No
Age Range:Any
Updated:3/24/2019
Start Date:January 2010
End Date:September 2013

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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.

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)
We found this trial at
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201 Dowman Dr
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1720 2nd Ave S
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800 Washington St
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5323 Harry Hines Blvd
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(214) 648-3111
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5050 Anthony Wayne Dr
Detroit, Michigan 48201
(313) 577-2424
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3040 East Cornwallis RoadTriangle
Durham, North Carolina 27705
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Durham, North Carolina 27710
(919) 684-8111
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7000 Fannin St
Houston, Texas 77030
(713) 500-4472
University of Texas Health Science Center at Houston The University of Texas Health Science Center...
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425 University Blvd.
Indianapolis, Indiana 46202
(317) 274-4591
Indiana University INDIANA UNIVERSITY is a major multi-campus public research institution, grounded in the liberal...
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101 Jessup Hall
Iowa City, Iowa 52242
(319) 335-3500
University of Iowa With just over 30,000 students, the University of Iowa is one of...
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60 Crittenden Blvd # 70
Rochester, New York 14642
(585) 275-2121
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201 Presidents Circle
Salt Lake City, Utah 84108
801) 581-7200
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Albuquerque, New Mexico 87131
(505) 277-0111
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New Haven, Connecticut 6520
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Yale University Yale's roots can be traced back to the 1640s, when colonial clergymen led...
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Palo Alto, California 94304
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