- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01030575
Multi-dose Pharmacokinetics and Dose Ranging of Inositol in Premature Infants (INS-2) (INS-2)
Phase II Randomized, Double-Masked, Placebo-Controlled, Safety, Pharmacokinetic, and Dose-Ranging Study of Multiple Doses of Inositol in Premature Infants
Study Overview
Status
Conditions
Intervention / Treatment
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 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35233
- University of Alabama at Birmingham
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California
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Palo Alto, California, United States, 94304
- Stanford University
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Connecticut
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New Haven, Connecticut, United States, 06504
- Yale University
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Georgia
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Atlanta, Georgia, United States, 30303
- Emory University
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Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana University
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Iowa
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Iowa City, Iowa, United States, 52242
- University of Iowa
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Massachusetts
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Boston, Massachusetts, United States, 02111
- Tufts Medical Center
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Michigan
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Detroit, Michigan, United States, 48201
- Wayne State University
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New Mexico
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Albuquerque, New Mexico, United States, 87131
- University of New Mexico
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New York
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Rochester, New York, United States, 14642
- University of Rochester
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke University
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Durham, North Carolina, United States, 27705
- RTI International
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Ohio
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Cleveland, Ohio, United States, 44106
- Case Western Reserve University, Rainbow Babies and Children's Hospital
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Rhode Island
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Providence, Rhode Island, United States, 02905
- Brown University, Women & Infants Hospital of Rhode Island
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Texas
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Dallas, Texas, United States, 75235
- University Of Texas Southwestern Medical Center At Dallas
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Houston, Texas, United States, 77030
- University of Texas Health Science Center at Houston
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Utah
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Salt Lake City, Utah, United States, 84108
- University of Utah
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Inositol low volume
10 mg/kg/day Intravenous inositol 5%
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5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
Other Names:
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Experimental: Inositol mid-level volume
40 mg/kg/day Intravenous inositol 5%
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20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
Other Names:
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Experimental: Inositol high volume
80 mg/kg/day Intravenous inositol 5%
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40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
Other Names:
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Placebo Comparator: Placebo
Glucose 5% given in volumes equal to that of the comparator drug
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Glucose 5% given in volumes equal to that of the comparator drug
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Population Pharmacokinetics: V - Volume
Time Frame: 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.
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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.
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Population Pharmacokinetics: Cl - Clearance
Time Frame: 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.
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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.
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Population Pharmacokinetics: R - Endogenous Infusion Rate
Time Frame: 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.
|
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.
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Population Pharmacokinetics: k - Elimination Rate (Cl/V)
Time Frame: 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.
|
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.
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Population Pharmacokinetics: t1/2 - Half-Life (0.693/k)
Time Frame: 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.
|
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.
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Population Pharmacokinetics: E - Concentration Due to Endogenous Infusion (R/Cl)
Time Frame: 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.
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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.
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SD of Residual Error (mg/l)
Time Frame: 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.
|
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.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Any Retinopathy of Prematurity (ROP)
Time Frame: 18-22 month corrected age
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Any ROP is defined as ROP of any severity that is observed at 18-22 month corrected age
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18-22 month corrected age
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Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death
Time Frame: 18-22 month corrected age
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Number of participants with any Retinopathy of Prematurity (ROP) through 18-22 month corrected age or death
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18-22 month corrected age
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Number of Participants With Any Ophthalmologic Diagnosis
Time Frame: 18-22 month corrected age
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Any ophthalmologic diagnosis at 18-22 month corrected age
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18-22 month corrected age
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Number of Participants With Any Ophthalmologic Treatment
Time Frame: 18-22 month corrected age
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Any ophthalmologic treatment at 18-22 month corrected age
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18-22 month corrected age
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Number of Participants With Any Ophthalmologic Surgical Treatment
Time Frame: 18-22 month corrected age
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Any ophthalmologic surgical treatment at 18-22 month corrected age
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18-22 month corrected age
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Number of Participants With Any Ophthalmologic Medical Treatment
Time Frame: 18-22 month corrected age
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Any ophthalmologic medical treatment at 18-22 month corrected age
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18-22 month corrected age
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Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age
Time Frame: 18-22 month corrected age
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A composite outcome that measures the occurrence of neurodevelopmental impairment between birth and 18-22 months corrected age.
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18-22 month corrected age
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Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age or Death
Time Frame: 8-22 months corrected age.
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Moderate or Severe NDI defined as occurrence of any of the following: GMFCS level II or higher (severe is level 4 or 5), Bayley III cognitive composite score < 85 (severe is <70), Bayley III motor composite score < 85 (severe is <70), unilateral blind or bilateral blind, permanent hearing loss that does not permit child to understand directions of the examiner and communicate despite amplification with cochlear implant or hearing aid
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8-22 months corrected age.
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Number of Participants With Moderate or Severe Cerebral Palsy
Time Frame: 18-22 months corrected age.
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Cerebral palsy by severity category (absent/mild/moderate/severe).
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18-22 months corrected age.
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Number of Participants With Composite Motor Score Less Than 70
Time Frame: 18-22 months corrected age
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This is measured as a scored of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite motor score.
Higher scores indicate better performance.
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18-22 months corrected age
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Number of Participants With Composite Cognitive Score Less Than 70
Time Frame: 18-22 months corrected age.
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This is measured as a score of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score
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18-22 months corrected age.
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Number of Participants With Severe Hearing Impairment
Time Frame: 18-22 months corrected age.
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Defined as permanent hearing loss that does not permit child to understand directions of the examiner and communicate despite amplification with cochlear implant or hearing aid.
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18-22 months corrected age.
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Number of Participants With Severe Vision Loss
Time Frame: 18-22 Months Corrected Age
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Vision loss as diagnosed by an ophthalmologist as legally blind, and subdivided into "ophthalmic origin", or "not ophthalmic origin" (i.e., cortical blindness is non-ophthalmic in origin and indicates that there is no retinal detachment or other abnormal fundus or ocular finding, except optic atrophy.
Such cases will be considered central [neurologic] in origin.)
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18-22 Months Corrected Age
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Number of Participants With Gross Motor Function Greater Than or Equal to 2
Time Frame: 18 -22 months corrected age
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A Gross Motor Function Classification System (GMFCS) level of at least II (on a scale from level I to V, with I indicating normal gross motor function and higher levels indicating greater impairment).
Level II is defined as Infants maintain floor sitting but may need to use their hands for support to maintain balance.
Infants creep on their stomach or crawl on hands and knees with reciprocal leg movement.
Infants may pull to stand and take steps holding on to furniture.)
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18 -22 months corrected age
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Collaborators and Investigators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lung Diseases
- Eye Diseases
- Infant, Newborn, Diseases
- Retinal Diseases
- Body Weight
- Pregnancy Complications
- Obstetric Labor Complications
- Obstetric Labor, Premature
- Lung Injury
- Infant, Premature, Diseases
- Ventilator-Induced Lung Injury
- Premature Birth
- Birth Weight
- Retinopathy of Prematurity
- Bronchopulmonary Dysplasia
- Physiological Effects of Drugs
- Micronutrients
- Vitamins
- Vitamin B Complex
- Inositol
Other Study ID Numbers
- NICHD-NRN-0036-2
- U10HD036790 (U.S. NIH Grant/Contract)
- U10HD021364 (U.S. NIH Grant/Contract)
- U10HD021373 (U.S. NIH Grant/Contract)
- U10HD021385 (U.S. NIH Grant/Contract)
- U10HD027851 (U.S. NIH Grant/Contract)
- U10HD027853 (U.S. NIH Grant/Contract)
- U10HD027856 (U.S. NIH Grant/Contract)
- U10HD027871 (U.S. NIH Grant/Contract)
- U10HD027880 (U.S. NIH Grant/Contract)
- U10HD027904 (U.S. NIH Grant/Contract)
- U10HD034216 (U.S. NIH Grant/Contract)
- U10HD040492 (U.S. NIH Grant/Contract)
- U10HD040689 (U.S. NIH Grant/Contract)
- U10HD053089 (U.S. NIH Grant/Contract)
- U10HD053109 (U.S. NIH Grant/Contract)
- U10HD053119 (U.S. NIH Grant/Contract)
- U10HD053124 (U.S. NIH Grant/Contract)
- UL1RR024139 (U.S. NIH Grant/Contract)
- UL1RR025744 (U.S. NIH Grant/Contract)
- UL1RR024979 (U.S. NIH Grant/Contract)
- M01RR008084 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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