Study of the Effect of Beta-3 Adrenergic Receptor Agonists on Oxidative Stress and Signalling Pathways Implicated in Remodelling of the Uteroplacental Space: Experimental in Vitro Approach on Myometrial Tissue Explants

Pregnancy Clinical Trial

— STRESSOX  

Official title:

Study of the Effect of Beta-3 Adrenergic Receptor Agonists on Oxidative Stress and Signalling Pathways Implicated in Remodelling of the Uteroplacental Space: Experimental in Vitro Approach on Myometrial Tissue Explants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02862886
• Other study ID #: LIONNAIS-COUVREUR AOI 2009
• Status: Completed
• Phase: N/A
• First received: August 5, 2016
• Last updated: August 10, 2016
• Start date: July 2010

Study information

• Verified date: May 2011
• Source: Centre Hospitalier Universitaire Dijon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

CHRONOLOGICAL DESCRIPTION OF THE STUDY

1. Information provided to study participants

2. Collection of written informed consent

3. Harvesting of myometrial biopsies

4. Creation of tissue explants using myometrial biopsies

5. Stimulation of the explants with LPS

6. Study of the effect of SAR150640 (beta3-adrenergic agonist) on LPS-induced oxidative stress Moreover, demonstrating the ability of beta3-adrenergic receptor agonists to prevent the appearance of oxidative stress and its consequences on tissues, as a complement to previous studies, is an additional argument for the clinical development of this class of pharmaceuticals in the management of threatened premature delivery and labour induction.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed informed consent

• Patients with national health insurance cover

• Patients with a normal pregnancy requiring a caesarean section for obstetrical reasons

• No obvious infectious context

Exclusion Criteria:

• Obvious inflammatory or autoimmune diseases

• Suspected or confirmed infectious context, including HIV, HCV HBV

• Coagulation disorders

• Preexisting or gestational diabetes

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Pregnancy

Intervention

Other:
• myometrium biopsy

Locations

Country	Name	City	State
France	CHU Dijon Bourgogne	Dijon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Dijon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	simultaneous assays of 4-amino-5-methylamino-2,7-difluorescein (DAF) / Dihydroethidium (DHE) markers by the technique of high pressure liquid chromatography	In vitro measurement of the ability of SAR150640 to prevent the release of free radicals (oxidative stress) induced by an inflammatory stimulus on tissue explants of the human myometrium. The level of oxidative stress will be determined using simultaneous assays of DAF/DHE using HPLC. This reference technique for the overall evaluation of oxidative stress is perfectly mastered at the LPPCE (Laboratoire de Physiopathologie et Pharmacologie Cardiovasculaire et Experimentales)	The biopsy of myometrium is done specifically for this study in a surgical unit after delivery of the child, in women with a normal pregnancy but requiring a caesarean	No
Secondary	Characterization of signalling pathways induced by oxidative stress during inflammation	Characterization of the implication of NADPH oxidase (luminometry) and the subunits of NADPH oxidase (gp91, p22fox, p67phox, p47phox, p40phox as well as Rac1/2) and NO synthases (eNOS & iNOS), as the source of the oxidative stress induced by an inflammatory stimulus, using Western blot	The biopsy of myometrium is done specifically for this study in a surgical unit after delivery of the child, in women with a normal pregnancy but requiring a caesarean	No