mtDNA as Novel Biomarker for Intra-amniotic Infection

Preterm Premature Rupture of Membrane Clinical Trial

— mtDNA  

Official title:

Circulating Cell-free Mitochondrial as a Novel Biomarker for Intra-amniotic Infection in Obstetrics

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03306719
• Other study ID #: 1115/2017
• Status: Recruiting
• Phase: N/A
• First received: October 1, 2017
• Last updated: October 10, 2017
• Start date: April 5, 2017
• Est. completion date: December 31, 2018

Study information

• Verified date: October 2017
• Source: Medical University of Vienna
• Contact: Herbert Kiss, MD, PhD
• Phone: +43140400
• Email: herbert.kiss[@]meduniwien.ac.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Finding a predictive biomarker for IAI could improve the clinical outcome for the mother and the neonate. The aim of this study is to quantify the copy number of circulating cell-free mitochondrial DNA in maternal serum and the placenta compared to controls.the investigators hypothesise that circulating cell-free mitochondrial DNA levels could help predict the likelihood of early inflammation in IAI. In addition, mitochondrial DNA could be a promotor triggering the pathogenesis of systemic inflammation.

Description:

Background: Intra-amniotic infection (IAI) or chorioamnionitis is a common condition seen in obstetrics leading to labor abnormalities such as uterine atony, postpartum bleeding and preterm labor (Schrag et al., 2006). Further adverse effects such as perinatal death, asphyxia, sepsis, pneumonia, respiratory distress and especially neurodevelopmental delay and cerebral palsy are associated with IAI (Buhimschi et al., 2009; Holzman, Lin, Senagore, & Chung, 2007). Diagnosing IAI can be challenging due to its very heterogeneous clinical signs, which are often very insensitive for this condition. Clinical findings such as fever, tachycardia and maternal leukocytosis leave room for multiple differential diagnoses. During apoptosis (due to hypoxia, cell damage or infection) the cell membrane integrity is disturbed, releasing the cytoplasm into the blood circulation. Circulating cell-free mitochondrial DNA acts as a damage associated molecular pattern (DAMP) by activating the innate immune system leading to inflammation (Matzinger, 1994). These DAMPs are evolutionary conserved and have structural similarity to their bacterial ancestor (Zhang et al., 2010). Therefore, cell-free mitochondria can act as a potent agent triggering the immune system in an autoimmune manner as well as a biomarker for cell damage due to infection.

Objective: Finding a predictive biomarker for IAI could improve the clinical outcome for the mother and the neonate. The aim of this study is to quantify the copy number of circulating cell-free mitochondrial DNA in maternal serum and the placenta compared to controls. Investigators hypothesize that circulating cell-free mitochondrial DNA levels could help predict the likelihood of early inflammation in IAI. In addition, mitochondrial DNA could be a promotor triggering the pathogenesis of systemic inflammation.

Methods: For this study the investiagtors planned 2 groups each consisting of 30 patients. The control group are pregnant women without IAI. The intervention group will be women with premature preterm rupture of membranes (pProm), suffering from IAI (meeting the diagnostic criteria for IAI suggested by the National Institute of Child Health and Human Development Workshop). 12ml of venous blood will be drawn from a peripheral venous line in addition to routine blood tests, when the patient arrives at the ward (2 weeks before delivery). A further 12ml of venous blood will be taken from the peripheral venous line, during delivery (during delivery). In addition, 12ml of venous blood will be drawn from the placenta postpartum. In total, 36 ml of blood will be withdrawn in each patient. Circulating cell-free mitochondrial DNA will be quantified in maternal and placental serum by real time quantitative PCR and statistical analysis will be performed by non-parametric tests.

Design: Single center, prospective, observational pilot trial.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2018
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Pregnant women 2 weeks before scheduled elective caesarian section at term (control group)

• Pregnant women in week 22+0 until week 28+0 who are admitted because of pPROM (intervention group)

• aged between 18 and 45 years

• Provide signed and dated informed consent

Exclusion Criteria:

• Women younger than 18 years

• No written consent

• Patients suffering from any autoimmune disease

Related Conditions & MeSH terms

• Fetal Membranes, Premature Rupture
• Preterm Premature Rupture of Membrane
• Rupture

Intervention

Biological:
• Blood sampling
Serial blood sampling

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mtDNA in Plasma		through study completion, an average of 1 year