NCT01030575

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
125

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2010

Typical duration for phase_2

Geographic Reach
1 country

17 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 10, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 11, 2009

Completed
21 days until next milestone

Study Start

First participant enrolled

January 1, 2010

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2011

Completed
2.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2013

Completed
7.5 years until next milestone

Results Posted

Study results publicly available

March 12, 2021

Completed
Last Updated

June 14, 2022

Status Verified

March 1, 2022

Enrollment Period

1.3 years

First QC Date

December 10, 2009

Results QC Date

December 23, 2020

Last Update Submit

May 18, 2022

Conditions

Infant, NewbornInfant, Low Birth WeightInfant, Small for Gestational AgeInfant, PrematureRetinopathy of PrematurityBronchopulmonary Dysplasia (BPD)

Keywords

NICHD Neonatal Research NetworkPharmacokineticsInositolVery Low Birth Weight (VLBW)Extremely Low Birth Weight (ELBW)Prematurity

Outcome Measures

Primary Outcomes (7)

  • Population Pharmacokinetics: V - Volume

    8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.

  • Population Pharmacokinetics: Cl - Clearance

    8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.

  • Population Pharmacokinetics: R - Endogenous Infusion Rate

    8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.

  • Population Pharmacokinetics: k - Elimination Rate (Cl/V)

    8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.

  • Population Pharmacokinetics: t1/2 - Half-Life (0.693/k)

    8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.

  • Population Pharmacokinetics: E - Concentration Due to Endogenous Infusion (R/Cl)

    8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.

  • SD of Residual Error (mg/l)

    8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.

Secondary Outcomes (14)

  • Number of Participants With Any Retinopathy of Prematurity (ROP)

    18-22 month corrected age

  • Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death

    18-22 month corrected age

  • Number of Participants With Any Ophthalmologic Diagnosis

    18-22 month corrected age

  • Number of Participants With Any Ophthalmologic Treatment

    18-22 month corrected age

  • Number of Participants With Any Ophthalmologic Surgical Treatment

    18-22 month corrected age

  • +9 more secondary outcomes

Study Arms (4)

Inositol low volume

EXPERIMENTAL

10 mg/kg/day Intravenous inositol 5%

Drug: Inositol lower volume

Inositol mid-level volume

EXPERIMENTAL

40 mg/kg/day Intravenous inositol 5%

Drug: Inositol mid-level volume

Inositol high volume

EXPERIMENTAL

80 mg/kg/day Intravenous inositol 5%

Drug: Inositol high volume

Placebo

PLACEBO COMPARATOR

Glucose 5% given in volumes equal to that of the comparator drug

Drug: Placebo low volume

Interventions

Inositol lower volumeDRUG

5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes

Also known as: Myo-inositol 5%
Inositol low volume
Inositol mid-level volumeDRUG

20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes

Also known as: Myo-inositol 5%
Inositol mid-level volume
Inositol high volumeDRUG

40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes

Also known as: Myo-inositol 5%
Inositol high volume
Placebo low volumeDRUG

Glucose 5% given in volumes equal to that of the comparator drug

Also known as: Dextrose
Placebo

Eligibility Criteria

Age12 Hours - 72 Hours
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • /7 to 26 6/7 weeks gestational age (48 infants) or
  • /7 to 29 6/7 weeks gestational age (48 infants)
  • grams birth weight or larger
  • hours of age

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Yale University

New Haven, Connecticut, 06504, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (1)

  • Phelps DL, Ward RM, Williams RL, Nolen TL, Watterberg KL, Oh W, Goedecke M, Ehrenkranz RA, Fennell T, Poindexter BB, Cotten CM, Hallman M, Frantz ID 3rd, Faix RG, Zaterka-Baxter KM, Das A, Ball MB, Lacy CB, Walsh MC, Carlo WA, Sanchez PJ, Bell EF, Shankaran S, Carlton DP, Chess PR, Higgins RD. Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants. Pediatr Res. 2016 Aug;80(2):209-17. doi: 10.1038/pr.2016.97. Epub 2016 Apr 13.

    PMID: 27074126RESULT

Related Links

MeSH Terms

Conditions

Premature BirthRetinopathy of PrematurityBronchopulmonary Dysplasia

Interventions

Glucose

Condition Hierarchy (Ancestors)

Obstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesRetinal DiseasesEye DiseasesInfant, Premature, DiseasesInfant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesVentilator-Induced Lung InjuryLung InjuryLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

HexosesMonosaccharidesSugarsCarbohydrates

Results Point of Contact

Title
Dr. Abhik Das
Organization
RTI International
adas@rti.org
301-770-8214

Study Officials

  • 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

    Children's Hospital Medical Center, Cincinnati

    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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 10, 2009

First Posted

December 11, 2009

Study Start

January 1, 2010

Primary Completion

May 1, 2011

Study Completion

September 1, 2013

Last Updated

June 14, 2022

Results First Posted

March 12, 2021

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will share

NDASG

Locations

US(17)