Correction of Neonatal Glutathione by N-acetylcysteine in Pregnant Women at Risk of Premature Birth (GSH MAP)

NCT03596125 | Terminated Phase 2

• 1 other identifier: RC15_0476
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Birth exposes the newborn to oxidative stress, as due to the switch from a protected, relatively hypoxic intrauterine milieu into an environment with a high oxygen pressure. The full-term newborn is well prepared to this massive redox challenge at the time of birth due to his well-integrated antioxidant defenses. On the contrary, numerous bibliographical data and our own work demonstrate the fragility of preterm newborns in this context of oxidative stress, linked to the immaturity of his antioxidant defenses. Premature birth abruptly propels the fetus from the protected, relatively hypoxic intrauterine milieu to an environment at risk of free radical injury caused by mechanical ventilation strategies, including the use of high inspired oxygen fractions or inhaled nitric oxide, generating excessive reactive oxidative species (ROS). Several studies highlight the key role of ROS in adverse outcomes of preterm infant suffering from low birth weight, bronchopulmonary dysplasia, necrotizing enterocolitis or retinopathy. This project aims to evaluate a therapeutic anti-oxidative strategy in order to correct the oxidative status of preterm infants. The investigators propose an early intervention that consists in an antenatal maternal supplementation with N-acetylcysteine (NAC), the acetylated precursor of both cysteine and glutathione, a key physiological antioxidant. This strategy could be promising for the development of simplified and personalized care of preterm infants. GSH MAP is a randomized, single-blind, placebo-controlled study that aims to determine if NAC supplementation in women admitted to hospital care due to preterm labor (prior to 34 weeks of gestational age) may correct glutathione deficiency in neonatal cord blood.

Conditions

Preterm Delivery

Keywords

Glutathione; Antioxidant; Oxidative stress; Preterm

Outcome Measures

Primary Outcomes (1)

• Venous umbilical cord blood concentration of glutathione (micromoles/L) following antenatal NAC supplementation.

  The venous umbilical cord blood concentration of glutathione will be measured in red blood cell lysates on C18-reverse phase column using liquid-chromatography combined to mass spectrometry. Homocysteine, cysteine, reduced (GSH) and oxidized (GSSG) glutathione levels will be measured in erythrocytes by comparing an experimental arm versus a placebo arm

  13 weeks

Secondary Outcomes (15)

• Number of days between the NAC-therapeutic initialization and childbirth.

  until childbirth

• Glutathione concentration in arterial blood at birth

  13 weeks

• Maternal blood concentrations of glutathione (micromoles/L) and their total antioxidant capacity at inclusion.

  18 weeks

• Maternal blood concentrations of glutathione (micromoles/L) and their total antioxidant capacity at delivery, following antenatal NAC supplementation.

  18 weeks

• Placental total antioxidant capacity at delivery

  at delivery

Study Arms (2)

N-acetylcysteine (NAC)

EXPERIMENTAL

High risk of prematurity: 9g intravenously then 6g (per os) a day until day 7, then 1,8g (per os) a day until 37 weeks of gestational age. Moderate risk of prematurity: 6g (per os) a day until day 7 then 1,8g ( per os) a day until 37 weeks of gestational age.

Drug: N-acetylcysteine

Placebo

PLACEBO COMPARATOR

High risk of prematurity: 9g intravenously then 6g (per os) a day until day 7, then 1,8g (per os) a day until 37 weeks of gestational age. Moderate risk of prematurity: 6g (per os) a day until day 7 then 1,8g ( per os) a day until 37 weeks of gestational age.

Drug: Placebo

Interventions

N-acetylcysteine DRUG

N-acetylcysteine supplementation

Also known as: NAC

N-acetylcysteine (NAC)

Placebo DRUG

per os: jelly tablets Intravenous Route: Glucidion G5

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years old
• Moderate or severe risk of prematurity
• Mono-fetal pregnancy
• And a term of pregnancy \> = 24 weeks and \<34 weeks of gestation at diagnosis
• subjects affiliated with an appropriate social security system
• written signed informed consent form

You may not qualify if:

• Age \< 18 years old
• Major under trusteeship or curatorship
• Maternal refusal and / or Incapacity to understand the benefits and potential risks of the protocol and to sign an informed consent form.
• A sonographic cervix ≥ 20 mm
• Mothers WITH:
• A Body mass index less than 18 kg/m2 and greater than 40 kg/m2 before pregnancy
• Type I, II diabetes
• Epileptic disorders
• A history of asthma
• A hemorrhagic pathology
• Maternal infection (HIV, hepatitis B and C) other than chorioamnionitis
• Patients in labour treated with magnesium sulphate
• Multiple pregnancy
• A known allergy/ hypersensitivity to N-acetylcysteine
• Fetal pathology other than intrauterine growth retardation (such as: karyotype abnormality, malformation, intrauterine growth retardation \<10th percentile)

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

Chu de Nantes

Nantes, 44000, France

Location

MeSH Terms

Conditions

Premature Birth

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Alice Küster, Dr

  Nantes University Hospital Nantes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2018
• First Posted: July 23, 2018
• Study Start: November 5, 2018
• Primary Completion: November 11, 2021
• Study Completion: November 11, 2021
• Last Updated: December 19, 2022

Record last verified: 2022-12

Locations

FR (1)