Infant, NewbornCytokinesNCT01035697
Inflammatory Cytokines Associated With Perinatal Brain Injury
An observational study of Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 18 sites in United States.
Trial summary
This observational study assessed whether measurements of certain pro-inflammatory and anti-inflammatory cytokines in the blood (either singly or in combination) at birth and/or up to day of life 21 can predict cerebral palsy at 18-22 months corrected age. Read more about this study
- Who is it for?
- Ages Up to 72 hoursHealthy volunteers can take part
- Conditions the study is for
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age
- How many people
- 1,067 participants
- Where
- 18 sitesUnited States
- Study dates
- Jul 1999to May 2004
- Phase
- Observational
- 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 Up to 72 hours
- All sexes
- Healthy volunteers accepted
- Child
Study population: Infants 401-1,000 grams at birth of both genders and all racial/ethnic groups.
Who may be able to join
- Infants 401-1,000 grams at birth
Who cannot join
- >72 hours of age
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Emory University
Atlanta, Georgia, 30303
University of Alabama
Birmingham, Alabama, 35249-7335
Wake Forest University
Charlotte, North Carolina, 27157
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
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
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Tennessee
Memphis, Tennessee, 38163
University of Miami
Miami, Florida, 33136
Yale University
New Haven, Connecticut, 06504
Stanford University
Palo Alto, California, 94304
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of California at San Diego
San Diego, California, 92103-8774
About this study
Official title: A Study to Determine If Inflammatory Cytokines Are Associated With Perinatal Brain Injury and Long Term Neurodevelopmental Handicap or Death
This observational study assessed whether measurements of certain pro-inflammatory and anti-inflammatory cytokines in the blood (either singly or in combination) at birth and/or up to day of life 21 can predict cerebral palsy at 18-22 months corrected age.
Read the detailed description
Inflammatory cytokines [interleukin-1 (IL-1β), IL-8, IL-9, tumor necrosis factor-α (TNF-α), and RANTES] but not anti-inflammatory cytokines released during the perinatal period have been associated with the development of periventricular leukomalacia (PVL) and cerebral palsy (CP) in near term and term infants. However, because blood samples were obtained on any day between day 1 and 18, these data cannot distinguish between prenatal and postnatal effects on neurological outcome. Furthermore, very low birth weight infants who are at the highest risk have not been studies.
The goal of this study was to measure pro-inflammatory and anti-inflammatory cytokine levels at various times in the perinatal period (at birth up to day of life 21), since they may be elevated at different points in the disease process. Blood samples (whole blood spots, dried on filter paper) were obtained on day 1 within 4 hours after birth, and on days 3, 7, 14, and 21. Neurodevelopmental assessments were conducted at 18-22 months corrected age.
- Conditions
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Cerebral Palsy
- Keywords
- NICHD Neonatal Research Network, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity, Pro-inflammatory cytokines, Anti-inflammatory cytokines, Interleukin-1 (IL-1β), Interleukin-2 (IL-2), Interleukin-3 (IL-3), Interleukin-8 (IL-8), Interleukin-9 (IL-9), Tumor necrosis factor-α (TNF-α), Regulated upon Activation, Normal T-cell Expressed and Secreted (RANTES)
- Medical subject headings
- Premature Birth, Cerebral Palsy
What is being measured
The primary outcome is the main question the study is designed to answer.
Pro-cytokines increased and anti-inflammatory cytokines decreased
Measured: At birth and/or up to Day 3±1
Secondary outcomes (4)
Type and severity of CP and other neurodevelopmental handicaps, the appearance of PVL, and neonatal mortality
Measured: 18-22 months corrected age
Abnormal pro-inflammatory and anti-inflammatory cytokines at birth are associated with prenatal insults (e.g., chorioamnionitis, occult intrauterine infection, early-onset neonatal sepsis, perinatal asphyxia, early death)
Measured: At birth
Abnormal postnatal cytokine levels associated with postnatal insults (e.g., postnatal intraventricular hemorrhage, late-onset neonatal sepsis, bronchopulmonary dysplasia, chronic lung disease, and/or necrotizing enterocolitis)
Measured: Up to Day of life 21
Pro-inflammatory cytokine elevations at the time of a workup for possible sepsis occur in infants with a positive bacterial blood culture and those with negative blood cultures who are treated with a full course of antibiotics
Measured: Up to Day of life 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2009 (estimated)
- Study startJul 1999
- Primary completionJul 2002
- Study completionMay 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,067 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- Centers for Disease Control and Prevention, National Center for Research Resources (NCRR)
- Investigators
- William Oh, MD, Principal investigator, Brown University, Women & Infants Hospital of Rhode IslandMichele C. Walsh, MD MS, Principal investigator, Case Western Reserve University, Rainbow Babies & Children's HospitalRonald N. Goldberg, MD, Principal investigator, Duke UniversityBarbara J. Stoll, MD, Principal investigator, Emory UniversityJames A. Lemons, MD, Principal investigator, Indiana UniversityAbhik Das, PhD, Principal investigator, RTI InternationalDavid K. Stevenson, MD, Principal investigator, Stanford UniversityWaldemar A. Carlo, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01035697
- Sponsor's protocol ID
- NICHD-NRN-0022
- Other IDs
- U10HD027853, M01RR008084, U10HD040492, M01RR000030, U10HD027851, M01RR000039, U10HD027856, M01RR000750
- Acronym
- Cytokines
- Status last verified
- Mar 2019
- First submitted
- 17 Dec 2009
- Last updated
- 22 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Ambalavanan N, Carlo WA, D'Angio CT, McDonald SA, Das A, Schendel D, Thorsen P, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants. Pediatrics. 2009 Apr;123(4):1132-41. doi: 10.1542/peds.2008-0526.
PubMed 19336372Natarajan G, Shankaran S, McDonald SA, DAS A, Stoll BJ, Higgins RD, Thorsen P, Skogstrand K, Hougaard DM, Carlo WA; NICHD neonatal research network. Circulating beta chemokine and MMP 9 as markers of oxidative injury in extremely low birth weight infants. Pediatr Res. 2010 Jan;67(1):77-82. doi: 10.1203/PDR.0b013e3181c0b16c.
PubMed 19755933Sood BG, Madan A, Saha S, Schendel D, Thorsen P, Skogstrand K, Hougaard D, Shankaran S, Carlo W; NICHD neonatal research network. Perinatal systemic inflammatory response syndrome and retinopathy of prematurity. Pediatr Res. 2010 Apr;67(4):394-400. doi: 10.1203/PDR.0b013e3181d01a36.
PubMed 20032809Carlo WA, McDonald SA, Tyson JE, Stoll BJ, Ehrenkranz RA, Shankaran S, Goldberg RN, Das A, Schendel D, Thorsen P, Skogstrand K, Hougaard DM, Oh W, Laptook AR, Duara S, Fanaroff AA, Donovan EF, Korones SB, Stevenson DK, Papile LA, Finer NN, O'Shea TM, Poindexter BB, Wright LL, Ambalavanan N, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines and neurodevelopmental outcomes in extremely low birth weight infants. J Pediatr. 2011 Dec;159(6):919-25.e3. doi: 10.1016/j.jpeds.2011.05.042. Epub 2011 Jul 27.
PubMed 21798559
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Determine If Inflammatory Cytokines Are Associated With Perinatal Brain Injury and Long Term Neurodevelopmental Handicap or Death
- ClinicalTrials.gov ID
- NCT01035697
- Acronym / sponsor ID
- Cytokines / NICHD-NRN-0022
- Conditions
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Cerebral Palsy
- Keywords
- NICHD Neonatal Research Network, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity, Pro-inflammatory cytokines, Anti-inflammatory cytokines, Interleukin-1 (IL-1β), Interleukin-2 (IL-2)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,067 participants (actual)
- Lead sponsor
- NICHD Neonatal Research NetworkResearch network
- Collaborators
- Centers for Disease Control and Prevention, National Center for Research Resources (NCRR)
- Study start
- Jul 1999
- Primary completion
- Jul 2002 (actual)
- Study completion
- May 2004 (actual)
- First posted
- 21 Dec 2009 (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 observational study assessed whether measurements of certain pro-inflammatory and anti-inflammatory cytokines in the blood (either singly or in combination) at birth and/or up to day of life 21 can predict cerebral palsy at 18-22 months corrected age.
Detailed description
Inflammatory cytokines [interleukin-1 (IL-1β), IL-8, IL-9, tumor necrosis factor-α (TNF-α), and RANTES] but not anti-inflammatory cytokines released during the perinatal period have been associated with the development of periventricular leukomalacia (PVL) and cerebral palsy (CP) in near term and term infants. However, because blood samples were obtained on any day between day 1 and 18, these data cannot distinguish between prenatal and postnatal effects on neurological outcome. Furthermore, very low birth weight infants who are at the highest risk have not been studies.
The goal of this study was to measure pro-inflammatory and anti-inflammatory cytokine levels at various times in the perinatal period (at birth up to day of life 21), since they may be elevated at different points in the disease process. Blood samples (whole blood spots, dried on filter paper) were obtained on day 1 within 4 hours after birth, and on days 3, 7, 14, and 21. Neurodevelopmental assessments were conducted at 18-22 months corrected age.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 72 hours
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Infants 401-1,000 grams at birth of both genders and all racial/ethnic groups.
Key inclusion criteria (1 listed)
- Infants 401-1,000 grams at birth
Key exclusion criteria (1 listed)
- >72 hours of age
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Pro-cytokines increased and anti-inflammatory cytokines decreased
Time frame: At birth and/or up to Day 3±1
4 secondary outcomes
Type and severity of CP and other neurodevelopmental handicaps, the appearance of PVL, and neonatal mortality
Time frame: 18-22 months corrected age
Abnormal pro-inflammatory and anti-inflammatory cytokines at birth are associated with prenatal insults (e.g., chorioamnionitis, occult intrauterine infection, early-onset neonatal sepsis, perinatal asphyxia, early death)
Time frame: At birth
Abnormal postnatal cytokine levels associated with postnatal insults (e.g., postnatal intraventricular hemorrhage, late-onset neonatal sepsis, bronchopulmonary dysplasia, chronic lung disease, and/or necrotizing enterocolitis)
Time frame: Up to Day of life 21
Pro-inflammatory cytokine elevations at the time of a workup for possible sepsis occur in infants with a positive bacterial blood culture and those with negative blood cultures who are treated with a full course of antibiotics
Time frame: Up to Day of life 21
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 22 Mar 2019.
- Results publication: PubMed 19336372Ambalavanan N, Carlo WA, D'Angio CT, McDonald SA, Das A, Schendel D, Thorsen P, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants. Pediatrics. 2009 Apr;123(4):1132-41. doi: 10.1542/peds.2008-0526.
- Results publication: PubMed 19755933Natarajan G, Shankaran S, McDonald SA, DAS A, Stoll BJ, Higgins RD, Thorsen P, Skogstrand K, Hougaard DM, Carlo WA; NICHD neonatal research network. Circulating beta chemokine and MMP 9 as markers of oxidative injury in extremely low birth weight infants. Pediatr Res. 2010 Jan;67(1):77-82. doi: 10.1203/PDR.0b013e3181c0b16c.
- Results publication: PubMed 20032809Sood BG, Madan A, Saha S, Schendel D, Thorsen P, Skogstrand K, Hougaard D, Shankaran S, Carlo W; NICHD neonatal research network. Perinatal systemic inflammatory response syndrome and retinopathy of prematurity. Pediatr Res. 2010 Apr;67(4):394-400. doi: 10.1203/PDR.0b013e3181d01a36.
- Results publication: PubMed 21798559Carlo WA, McDonald SA, Tyson JE, Stoll BJ, Ehrenkranz RA, Shankaran S, Goldberg RN, Das A, Schendel D, Thorsen P, Skogstrand K, Hougaard DM, Oh W, Laptook AR, Duara S, Fanaroff AA, Donovan EF, Korones SB, Stevenson DK, Papile LA, Finer NN, O'Shea TM, Poindexter BB, Wright LL, Ambalavanan N, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines and neurodevelopmental outcomes in extremely low birth weight infants. J Pediatr. 2011 Dec;159(6):919-25.e3. doi: 10.1016/j.jpeds.2011.05.042. Epub 2011 Jul 27.
- 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.
William Oh, MD principal investigator
Brown University, Women & Infants Hospital of Rhode Island
Michele C. Walsh, MD MS principal investigator
Case Western Reserve University, Rainbow Babies & Children's Hospital
Ronald N. Goldberg, MD principal investigator
Duke University
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 18 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 1 inclusion and 1 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 22 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Pro-cytokines increased and anti-inflammatory cytokines decreased (time frame: At birth and/or up to Day 3±1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01035697, which also lists 4 linked publications.
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 22 Mar 2019.