Infant, NewbornPhase 2INS-1NCT00349726
Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants
A Phase 2 study testing Inositol lower volume and Inositol higher volume in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 6 days
- Conditions the study is for
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age
- What is being tested?
- Inositol lower volume and Inositol higher volume
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 11 sitesUnited States
- Study dates
- Jun 2006to Dec 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 6 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
RTI International
Durham, North Carolina, 27705
Duke University
Durham, North Carolina, 27710
Indiana University
Indianapolis, Indiana, 46202
Yale University
New Haven, Connecticut, 06504
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of Rochester
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84108
About this study
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.
Read the 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.
- Conditions
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Retinopathy of Prematurity, Bronchopulmonary Dysplasia (BPD)
- Being tested
- Inositol lower volume, Inositol higher volume, Placebo lower volume, Placebo higher volume
- Keywords
- NICHD Neonatal Research Network, Pharmacokinetics, Inositol, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity
- Medical subject headings
- Premature Birth, Retinopathy of Prematurity, Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inositol lower volumeDrug
60 mg/kg (1.2ml/kg) of myo-inositol 5% given intravenously over 20 minutes.
Inositol higher volumeDrug
120 mg/kg (2.4ml/kg) of myo-inositol 5% given intravenously over 20 minutes.
Placebo lower volumeDrug
60 mg/kg (1.2ml/kg) of glucose 5% given intravenously over 20 minutes.
Placebo higher volumeDrug
120 mg/kg (2.4ml/kg) of glucose 5% given intravenously over 20 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Inositol low volume | Experimental | Single dose of intravenous inositol 5%, 60 mg/kg (1.2ml/kg) given over 20 minutes Receives: Drug: Inositol lower volume |
| Inositol high volume | Experimental | Single dose of intravenous inositol 5%, 120 mg/kg (2.4ml/kg) given over 20 minutes Receives: Drug: Inositol higher volume |
| Placebo low volume | Placebo comparator | Placebo (5% glucose) at a volume equal to 60 mg/kg (1.2 ml/kg) given via IV over 20 minutes. Receives: Drug: Placebo lower volume |
| Placebo high volume | Placebo comparator | Placebo (5% glucose) at a volume equal to 120 mg/kg (2.4 ml/kg) given via IV over 20 minutes Receives: Drug: Placebo higher volume |
What is being measured
The primary outcome is the main question the study is designed to answer.
Population pharmacokinetics
Measured: 0-100 hours following infusion
Secondary outcomes (1)
Adverse events during and following infusion, using a neonatal toxicity classification
Measured: Until discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2006 (estimated)
- Study startJun 2006
- Primary completionDec 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infant, NewbornStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- 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)
- Responsible party
- Sponsor
- Investigators
- Abbot R. Laptook, MD, Principal investigator, Brown University, Women & Infants Hospital of Rhode IslandMichele C. Walsh, MD MS, Principal investigator, Case Western Reserve University, Rainbow Babies and Children's HospitalRonald N. Goldberg, MD, Principal investigator, Duke UniversityBrenda B. Poindexter, MD MS, Principal investigator, Indiana UniversityAbhik Das, PhD, Principal investigator, RTI InternationalKristi L. Watterberg, MD, Principal investigator, University of New MexicoDale L. Phelps, MD, Principal investigator, University of RochesterPablo J. Sanchez, MD, Principal investigator, University of Texas, Southwestern Medical Center at Dallas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00349726
- Sponsor's protocol ID
- NICHD-NRN-0036-1
- Other IDs
- U10HD021364, U10HD021373, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880
- Acronym
- INS-1
- Status last verified
- Jun 2017
- First submitted
- 6 Jul 2006
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants
- ClinicalTrials.gov ID
- NCT00349726
- Acronym / sponsor ID
- INS-1 / NICHD-NRN-0036-1
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- NICHD Neonatal Research NetworkResearch network
- Collaborators
- National Eye Institute (NEI), National Center for Research Resources (NCRR), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jun 2006
- Primary completion
- Dec 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 10 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Inositol low volume | Experimental | Drug: Inositol lower volumeSingle dose of intravenous inositol 5%, 60 mg/kg (1.2ml/kg) given over 20 minutes |
| Inositol high volume | Experimental | Drug: Inositol higher volumeSingle dose of intravenous inositol 5%, 120 mg/kg (2.4ml/kg) given over 20 minutes |
| Placebo low volume | Placebo comparator | Drug: Placebo lower volumePlacebo (5% glucose) at a volume equal to 60 mg/kg (1.2 ml/kg) given via IV over 20 minutes. |
| Placebo high volume | Placebo comparator | Drug: Placebo higher volumePlacebo (5% glucose) at a volume equal to 120 mg/kg (2.4 ml/kg) given via IV over 20 minutes |
Who may qualify
- Ages
- 3 to 6 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inositol lower volume60 mg/kg (1.2ml/kg) of myo-inositol 5% given intravenously over 20 minutes. | Drug | Inositol low volume |
| Inositol higher volume120 mg/kg (2.4ml/kg) of myo-inositol 5% given intravenously over 20 minutes. | Drug | Inositol high volume |
| Placebo lower volume60 mg/kg (1.2ml/kg) of glucose 5% given intravenously over 20 minutes. | Drug | Placebo low volume |
| Placebo higher volume120 mg/kg (2.4ml/kg) of glucose 5% given intravenously over 20 minutes. | Drug | Placebo high volume |
Primary outcome
Population pharmacokinetics
Time frame: 0-100 hours following infusion
1 secondary outcome
Adverse events during and following infusion, using a neonatal toxicity classification
Time frame: Until discharge
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- NICHD Neonatal Research NetworkLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abbot R. Laptook, MD principal investigator
Brown University, Women & Infants Hospital of Rhode Island
Michele C. Walsh, MD MS principal investigator
Case Western Reserve University, Rainbow Babies and Children's Hospital
Ronald N. Goldberg, MD principal investigator
Duke University
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Inositol lower volume and Inositol higher volume in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Population pharmacokinetics (time frame: 0-100 hours following infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2017.