Genetic Variants and Susceptibility to Diseases of Prematurity in Very Low Birth-Weight Infants (CLD)

January 23, 2026 updated by: G. Ganesh Konduri, Medical College of Wisconsin
The purpose of this study is to determine if sequence variations in genes involved in the development and function of vulnerable organs increases susceptibility to chronic lung disease (CLD) and other diseases affecting premature infants, such as necrotizing enterocolitis (NEC), sepsis, patent ductus arteriosus (PDA) and intraventricular hemorrhage (IVH). The study will also determine whether measurement of certain biomarkers in serum will identify infants who will develop these complications of prematurity. Previous studies from this institution and others have identified genetic variants in some genes, such as toll like receptor genes are associated with higher risk of CLD or NEC. The interaction of these variants with other gene variants that can influence the risk of these diseases remains unclear.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Chronic lung disease of prematurity (CLD) is diagnosed in 30-40% of very low birth weight (VLBW) infants (<1500gms) and remains a leading cause of mortality and long-term morbidity in this population. Other diseases such as necrotizing enterocolitis (NEC), sepsis, patent ductus arteriosus (PDA), and intraventricular hemorrhage (IVH) also contribute to mortality and morbidity in this population. A central tenet in the pathogenesis of NEC, CLD and sepsis is the failure of host genome-regulated immune defenses to surmount the challenges posed by microbial pathogens in the presence of risk-factors that induce intestinal, pulmonary and systemic injury, respectively. Toll like receptors (TLRs) are pathogen recognition receptors which serve as the recognition and effector arm of the innate immune system. Since the premature infant is predominantly dependent on the innate immune system for host defense our hypothesis is that hypomorphic genetic variations in TLRs will increase susceptibility to diseases of prematurity such as CLD and sepsis.The increased risk of inflammation, decreased potential for repair and growth of lung may be reflected in the levels of biomarkers, such as, cytokines, micro-RNAs (miRNA) or peptides that are secreted into biological fluids, like blood and tracheal aspirates. It is likely that the genetic variants that increase the risk of inflammation or decreased repair and growth will be also associated with altered levels of these biomarkers. Measurement of the biomarkers and genetic variants together can increase the precision of the early predictors of these complications of prematurity. Measurement of biomarkers in biological fluids can be done with a shorter turnaround time than gene sequencing at the present time. Biomarkers can also provide longitudinal changes in the severity of disease and response to therapy. Newer multiplex assays make it feasible to measure the levels of biomarkers in very small quantities of biological fluids. These complementary strengths make gene sequencing and biomarker detection ideal 1-2 approach for the early identification and disease progression evaluation in premature infants. Our hypothesis will be tested in VLBW infants in four specific aims: (1) To determine whether the presence of previously described single nucleotide polymorphisms (SNPs) in TLR4 (Asp299Gly, Thr399Ile) TLR2 (Arg753Gln) and TLR5 (Arg392STOP) genes is associated with an increased risk of CLD ; (2) to detect by DNA sequencing if novel genetic variations in TLR4, TLR2, TLR9, MyD88 and other innate immune genes increases the risk of CLD or other disease in premature infants; (3) to identify by gene sequence approach whether variants in other repair and growth genes alter susceptibility to diseases affecting premature infants such as CLD,NEC or sepsis or PDA or IVH; and (4) whether alterations in cytokines, miRNA and other biomarker levels in serum from the same blood samples can provide additional predictive value in recognizing the risk of diseases of prematurity. VLBW infants who develop CLD (oxygen requirement at 36 weeks postconceptional age), NEC, sepsis, PDA, or IVH will serve as cases while VLBW infants who do not develop the diseases of interest will serve as controls. A 0.5cc sample of blood will be collected from enrolled infants via indwelling catheter or heel-stick for DNA analysis after consent is obtained. The TLR4 (Asp299Gly, Thr399Ile) TLR2 (Arg753Gln) and TLR5 (Arg392STOP) SNPs will be evaluated using a multiplex Single Base extension based technique, using commercially available primers. Novel genetic variations in these genes of interest and other variants proposed to be related to NEC will be detected using conventional Sanger or Next Generation DNA sequencing. Serum will be separated from the same blood sample obtained for DNA isolation. A second 0.5cc sample of blood will be collected for biomarker measurement. Biomarker levels in serum will be analyzed using multiplex EIA for cytokines, sequencing for miRNA profile and ELISA for peptide levels of interest (VEGF, angiopoietin-2 and Nogo-B peptide). Benefits include the possibility of development of risk-based preventive and therapeutic strategies to prevent CLD, NEC, sepsis, PDA, or IVH in this population.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: G. Ganesh Konduri, MD
  • Phone Number: 414.266.6820
  • Email: gkonduri@mcw.edu

Study Contact Backup

  • Name: Kathleen M Meskin, BSN
  • Phone Number: 414.337.7171
  • Email: kmeskin@mcw.edu

Study Locations

  • United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Children's Wisconsin
        • Contact:
        • Principal Investigator:
          • G. Ganesh Konduri, MD
        • Contact:
          • Kathleen Meskin, RN, BSN
          • Phone Number: 414-337-7171
          • Email: kmeskin@mcw.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Infants born weighing less than 1500 grams

Description

Inclusion Criteria:

  • Infants born weighing less than 1500 grams

Exclusion Criteria:

  • Infants born with congenital heart disease (other than patent ductus arteriosus)
  • major congenital anomalies of the GI tract, respiratory tract, or kidneys

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
VLBW
infants less than 1500 grams at birth
Genetic: gene variations
comparing variations in genes in infants who develop chronic lung disease and other diseases of prematurity and those who do not.
Other Names:
  • toll like receptors, biomarkers

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
To determine if small variations in certain genes predispose infants to the development of chronic lung disease and other diseases of prematurity
Time Frame: participants will be followed for the duration of hospital stay, an expected average of 6 to 8 weeks
participants will be followed for the duration of hospital stay, an expected average of 6 to 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical College of Wisconsin

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: G. Ganesh Konduri, MD, Medical College of Wisconsin

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2006

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 19, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 3, 2008

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 4, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 26, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRO44242

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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