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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2015 by Medical College of Wisconsin
Sponsor:
Information provided by (Responsible Party):
G. Ganesh Konduri, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT00710112
First received: June 19, 2008
Last updated: September 2, 2015
Last verified: September 2015
  Purpose
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 CLD and other diseases affecting premature infants, such as necrotizing enterocolitis (NEC), sepsis, patent ductus arteriosus (PDA) and intraventricular hemorrhage (IVH).

Condition Intervention
Chronic Lung Disease
Genetic: gene variations

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genetic Variants and Susceptibility to Diseases of Prematurity in Very Low Birth-Weight Infants

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA
whole blood

Estimated Enrollment: 800
Study Start Date: June 2006
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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 Name: toll like receptors

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. Our hypothesis will be tested in VLBW infants in three specific aims: 1) to determine if 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 diseases in premature infants; and 3) to identify by genome-based approaches whether other genetic variants alter susceptibility to diseases affecting premature infants such as CLD, NEC, sepsis, PDA, or IVH. 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. 0.5 ml of blood will be collected from enrolled infants via indwelling catheters or venipuncture for DNA analysis after consent is obtained. The detection of TLR4 (Asp299Gly, Thr399Ile) TLR2 (Arg753Gln) and TLR5 (Arg392STOP) SNPs will be done using a multiplex Single Base extension based technique. Novel genetic variations in the genes of interest and others proposed to be related to NEC will be detected using conventional Sanger or Next Generation DNA sequencing. Benefits include the possibility of development of risk-based preventive and therapeutic strategies to prevent CLD, NEC, sepsis, PDA, or IVH in this population.
  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Infants born weighing less than 1500 grams
Criteria

Inclusion Criteria:

  • Infants born weighing less than 1500grams

Exclusion Criteria:

  • Infants born with congenital heart disease (other than patent ductus arterioses)
  • major congenital anomalies of the GI tract, renal or respiratory tract
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00710112

Contacts
Contact: G. Ganesh Konduri, MD 414.266.6820 gkonduri@mcw.edu
Contact: Kathleen M Meskin, BSN 414.337.7171 kmeskin@mcw.edu

Locations
United States, Wisconsin
Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: G. Ganesh Konduri, MD    414-266-6820    gkonduri@mcw.edu   
Contact: Kathleen Meskin, RN, BSN       kmeskin@mcw.edu   
Principal Investigator: G. Ganesh Konduri, MD         
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
Principal Investigator: G. Ganesh Konduri, MD Medical College of Wisconsin
  More Information

Responsible Party: G. Ganesh Konduri, Chief, Division of Neonatology; Professor, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00710112     History of Changes
Other Study ID Numbers: CHW 06/92, GC151 
Study First Received: June 19, 2008
Last Updated: September 2, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Medical College of Wisconsin:
CLD
VLBW infants
Toll like Receptors

Additional relevant MeSH terms:
Lung Diseases
Birth Weight
Premature Birth
Disease Susceptibility
Respiratory Tract Diseases
Body Weight
Signs and Symptoms
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on July 24, 2016