Genetic Variations in Toll-like Receptors and Susceptibility to Chronic Lung Disease in Very Low Birth Weight Babies (CLD)

This study is currently recruiting participants.
Verified August 2013 by Medical College of Wisconsin
Sponsor:
Collaborators:
Wheaton Franciscan Healthcare
Children's Hospitals and Clinics of Minnesota
Waukesha Memorial Hospital
Information provided by (Responsible Party):
Venkatesh Sampath, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT00710112
First received: June 19, 2008
Last updated: August 28, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to determine whether genetic variations in the immune system influence susceptibility to infection and chronic lung disease in premature infants.


Condition Intervention
Chronic Lung Disease
Genetic: gene variations

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genetic Variations in Toll-like Receptors and Susceptibility to Chronic Lung Disease in Very Low Birth Weight Babies

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. [ Time Frame: through discharge from hospital ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

whole blood


Estimated Enrollment: 600
Study Start Date: June 2006
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (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 those who do not.
Other Name: toll like receptors

Detailed Description:

Chronic lung disease of prematurity (CLD) is diagnosed in >30% of Very low birth-weight infants (<1500gms) and is a major cause of mortality and long-term morbidity in this population. While multiple factors have been implicated in the pathogenesis of CLD, a body of evidence suggests that exposure to antenatal chorioamnionitis and postnatal infections substantially increase the risk of CLD. Environmental and genetic factors which increase susceptibility of the premature infant to infection mediated inflammation in the lung may result in CLD. 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 CLD. Our hypothesis will be tested in VLBW infants in two 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 and 2) To detect by DNA sequencing if novel genetic variations in TLR4, TLR2, TLR9 and MyD88 genes increases the risk of CLD. VLBW infants who develop CLD (oxygen requirement at 36 weeks postconceptional age) will serve as cases while VLBW infants who do not develop CLD will serve as controls. 1 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 will be detected using DNA sequencing. Benefits include the possibility of development of risk-based preventive and therapeutic strategies to prevent CLD, decreasing morbidity and mortality from the disease.

  Eligibility

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

Contacts
Contact: Venkatesh Sampath, MD 414.337.7162 vsampath@mcw.edu
Contact: Kathleen M Meskin, BSN 414.337.7171 kmeskin@mcw.edu

Locations
United States, Minnesota
Children's Hospitals and Clinics Recruiting
Minneapolis, Minnesota, United States, 55404
Contact: Neil Mulrooney, MD    612-813-6288    neil.mulrooney@childrensmn.org   
Contact: Cathy Worwa, BSN, RN    612.813.6864    Cathy.Worwa@childrensmn.org   
United States, Wisconsin
Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Venkatesh Sampath, MD       vsampath@mcw.edu   
Contact: Kathleen Meskin, RN, BSN       kmeskin@mcw.edu   
Principal Investigator: Venkatesh Sampath, MD         
Sponsors and Collaborators
Medical College of Wisconsin
Wheaton Franciscan Healthcare
Children's Hospitals and Clinics of Minnesota
Waukesha Memorial Hospital
Investigators
Principal Investigator: Venkatesh Sampath, MD Medical College of Wisconsin
Study Chair: Laura L Lane, BSN Medical College of Wisconsin
Study Chair: Kathleen M Meskin, BSN Medical College of Wisconsin
  More Information

No publications provided

Responsible Party: Venkatesh Sampath, Assistant Professor, Neonatology, 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: August 28, 2013
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Birth Weight
Disease Susceptibility
Lung Diseases
Body Weight
Signs and Symptoms
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 14, 2014