Preterm DeliveryPhase 2/3NCT03596125
Correction of Neonatal Glutathione by N-acetylcysteine in Pregnant Women at Risk of Premature Birth (GSH MAP)
A Phase 2/3 study testing N-acetylcysteine in people with Preterm Delivery, run by Nantes University Hospital at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Preterm Delivery
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 1 siteFrance
- Study dates
- 5 Nov 2018to 11 Nov 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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)
- Current high doses of antioxidants treatments (vitamin supplements, ...)
- Patient with proven pre-eclampsia
- Patient with heart failure
- Patient with nephropathy
- Patient with medically known lactose intolerance
- Patient not affiliated with an appropriate social security system
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Correction of Neonatal Glutathione by N-acetylcysteine in Pregnant Women at Risk of Premature Birth
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.
Read more
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.
Read the detailed description
GSH MAP is a randomized single-blind, placebo-controlled study. The design will include the recruitment of 120 pregnant women admitted to hospital care due to preterm labor (above 18 yrs of age, gestational age between 24 and 34 weeks). According to the risk of preterm delivery, women will be treated following two different schedules :
- High risk of prematurity: NAC supplementation -9 g intravenously-6g/day per os until day 7-1,8g/day per os until 37 weeks of gestational age.
- Moderate risk of prematurity: NAC supplementation -6g/day per os until day 7-1,8g/day per os until 37 weeks of gestational age.
Biological samples collected: maternal blood at inclusion, maternal/cord blood and placenta at delivery, breast milk samples during the first week of lactation in case of exclusive breastfeeding.
Levels of glutathione and related metabolites will be measured in plasma, red blood cells, placenta and breast milk.
In ancillary studies, metabolome and lipidome profilings will be performed on maternal and cord blood and on breast milk samples.
- Conditions
- Preterm Delivery
- Being tested
- N-acetylcysteine, Placebo
- Keywords
- Glutathione, Antioxidant, Oxidative stress, Preterm
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called NAC
N-acetylcysteine supplementation
PlaceboDrug
per os: jelly tablets Intravenous Route: Glucidion G5
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 13 weeks
Secondary outcomes (15)
Number of days between the NAC-therapeutic initialization and childbirth.
The delay time (days) between delivery and inclusion of pregnant women admitted to hospital care due to preterm labor will be compared in an experimental arm versus a placebo arm.
Measured: until childbirth
Glutathione concentration in arterial blood at birth
The arterial 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
Measured: 13 weeks
Maternal blood concentrations of glutathione (micromoles/L) and their total antioxidant capacity at inclusion.
Changes in glutathione concentration (micromoles/L) in maternal red blood cells will be measured at inclusion and compared in an experimental arm versus a placebo arm. The maternal blood concentration of glutathione will be assessed as in the primary outcome measurement description. Total antioxidant capacity of maternal blood will be measured in plasma using kits such as Trolox Equivalent Antioxidant Capacity (TEAC) assay or lipid-peroxide secretion, measured by TBARS levels, combined to the measurement of levels of oxidized (carbonylated) proteins by mass spectrometry.
Measured: 18 weeks
Maternal blood concentrations of glutathione (micromoles/L) and their total antioxidant capacity at delivery, following antenatal NAC supplementation.
Changes in glutathione concentration (micromoles/L) in maternal red blood cells will be measured at delivery and compared in an experimental arm versus a placebo arm. The maternal blood concentration of glutathione will be assessed as in the primary outcome measurement description. Total antioxidant capacity of maternal blood will be measured in plasma using kits such as Trolox Equivalent Antioxidant Capacity (TEAC) assay or lipid-peroxide secretion, measured by TBARS levels, combined to the measurement of levels of oxidized (carbonylated) proteins by mass spectrometry.
Measured: 18 weeks
Placental total antioxidant capacity at delivery
Placental gene expression patterns of various enzymes involved in oxidative status such as superoxide dismutase, catalase and glutathione peroxidase and reductase will be measured in an experimental arm versus a placebo arm. Levels of free radical scavengers such as glutathione will be measured using liquid-chromatography combined to mass spectrometry. Placental total antioxidant capacity will be measured using TEAC or TBARS assays, combined to the measurement of levels of oxidized (carbonylated) proteins.
Measured: at delivery
Breast milk sulphur amino acid pattern on day 7 of the postpartum period following NAC supplementation.
Colostrum or native breastmilk collected at day 7 will serve for determination of glutathione levels and other sulphur amino acids measured using liquid-chromatography combined to mass spectrometry.
Measured: 19 weeks
Total antioxidant capacity on day 7 of the postpartum period following NAC supplementation.
Total antioxidant capacity will be measured using TEAC or TBARS assays in combination with mass spectrometry assessment of oxidized (carbonylated) proteins.
Measured: 19 weeks
Maternal metabolome and lipidome at delivery following the antenatal NAC supplementation.
Metabolomic, lipidomic and amino acid patterns will be measured in maternal blood at GSH MAP-inclusion and at delivery using liquid-chromatography combined to mass spectrometry. The significance of the impact of NAC supplementation on these patterns will be assessed in link with maternal clinical data.
Measured: 18 weeks
Weight variations
Weight will be evaluated in the fetus by maternal ultra-sound scans and measured on the newborn at birth and during his hospital stay. The significance of the impact of antenatal NAC supplementation on the anthropometric fetal and newborn data will be assessed taking into account clinical data.
Measured: Hospital discharge (4 months)
Lenght variations
Length will be evaluated in the fetus by maternal ultra-sound scans and measured on the newborn at birth and during his hospital stay. The significance of the impact of antenatal NAC supplementation on the anthropometric fetal and newborn data will be assessed taking into account clinical data.
Measured: Hospital discharge (4 months)
Head circumference variations
Head circumference will be evaluated in the fetus by maternal ultra-sound scans and measured on the newborn at birth and during his hospital stay. The significance of the impact of antenatal NAC supplementation on the anthropometric fetal and newborn data will be assessed taking into account clinical data.
Measured: Hospital discharge (4 months)
Postnatal follow up of newborn blood concentration of glutathione during his first days of life.
Newborn blood currently collected for clinical assessment during hospitalization will be analyzed in order to determine glutathione using liquid-chromatography combined to mass spectrometry. .
Measured: from birth until hospital discharge (4 months)
Postnatal follow up of newborn blood concentration of total antioxidant capacity during his first days of life.
Newborn blood total antioxidant capacity will be measured using TEAC or TBARS assays.
Measured: from birth until hospital discharge (4 months)
Postnatal follow up of newborn blood concentration of and metabolome/lipidome during his first days of life.
Newborn blood currently collected for clinical assessment during hospitalization will be analyzed in order to determine metabolome/lipidome using liquid-chromatography combined to mass spectrometry.
Measured: from birth until hospital discharge (4 months)
Improvement of the clinical outcome of the newborn until discharge from hospital.
Clinical data in newborn until his discharge and frequency of postnatal pathologies associated with prematurity.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2018
- Study start5 Nov 2018
- Primary completion11 Nov 2021
- Study completion11 Nov 2021
Why it stopped: difficulty of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Preterm DeliveryStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alice Küster, Dr, Principal investigator, Nantes University Hospital Nantes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03596125
- Sponsor's protocol ID
- RC15_0476
- Status last verified
- Dec 2022
- First submitted
- 28 May 2018
- Last updated
- 19 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correction of Neonatal Glutathione by N-acetylcysteine in Pregnant Women at Risk of Premature Birth
- ClinicalTrials.gov ID
- NCT03596125
- Acronym / sponsor ID
- RC15_0476
- Conditions
- Preterm Delivery
- Keywords
- Glutathione, Antioxidant, Oxidative stress, Preterm
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: difficulty of recruitment
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 5 Nov 2018 (actual)
- Primary completion
- 11 Nov 2021 (actual)
- Study completion
- 11 Nov 2021 (actual)
- First posted
- 23 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
GSH MAP is a randomized single-blind, placebo-controlled study. The design will include the recruitment of 120 pregnant women admitted to hospital care due to preterm labor (above 18 yrs of age, gestational age between 24 and 34 weeks). According to the risk of preterm delivery, women will be treated following two different schedules :
- High risk of prematurity: NAC supplementation -9 g intravenously-6g/day per os until day 7-1,8g/day per os until 37 weeks of gestational age.
- Moderate risk of prematurity: NAC supplementation -6g/day per os until day 7-1,8g/day per os until 37 weeks of gestational age.
Biological samples collected: maternal blood at inclusion, maternal/cord blood and placenta at delivery, breast milk samples during the first week of lactation in case of exclusive breastfeeding.
Levels of glutathione and related metabolites will be measured in plasma, red blood cells, placenta and breast milk.
In ancillary studies, metabolome and lipidome profilings will be performed on maternal and cord blood and on breast milk samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| N-acetylcysteine (NAC) | Experimental | Drug: N-acetylcysteineHigh 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. |
| Placebo | Placebo comparator | Drug: PlaceboHigh 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (21 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: NACN-acetylcysteine supplementation | Drug | N-acetylcysteine (NAC) |
| Placeboper os: jelly tablets Intravenous Route: Glucidion G5 | Drug | Placebo |
Primary outcome
Venous umbilical cord blood concentration of glutathione (micromoles/L) following antenatal NAC supplementation.
Time frame: 13 weeks
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
15 secondary outcomes
Number of days between the NAC-therapeutic initialization and childbirth.
Time frame: until childbirth
Glutathione concentration in arterial blood at birth
Time frame: 13 weeks
Maternal blood concentrations of glutathione (micromoles/L) and their total antioxidant capacity at inclusion.
Time frame: 18 weeks
Maternal blood concentrations of glutathione (micromoles/L) and their total antioxidant capacity at delivery, following antenatal NAC supplementation.
Time frame: 18 weeks
Placental total antioxidant capacity at delivery
Time frame: at delivery
Breast milk sulphur amino acid pattern on day 7 of the postpartum period following NAC supplementation.
Time frame: 19 weeks
Total antioxidant capacity on day 7 of the postpartum period following NAC supplementation.
Time frame: 19 weeks
Maternal metabolome and lipidome at delivery following the antenatal NAC supplementation.
Time frame: 18 weeks
Weight variations
Time frame: Hospital discharge (4 months)
Lenght variations
Time frame: Hospital discharge (4 months)
Head circumference variations
Time frame: Hospital discharge (4 months)
Postnatal follow up of newborn blood concentration of glutathione during his first days of life.
Time frame: from birth until hospital discharge (4 months)
Postnatal follow up of newborn blood concentration of total antioxidant capacity during his first days of life.
Time frame: from birth until hospital discharge (4 months)
Postnatal follow up of newborn blood concentration of and metabolome/lipidome during his first days of life.
Time frame: from birth until hospital discharge (4 months)
Improvement of the clinical outcome of the newborn until discharge from hospital.
Time frame: 4 months
Results and safety
The study was stopped early (reason given: difficulty of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alice Küster, Dr principal investigator
Nantes University Hospital Nantes
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing N-acetylcysteine in people with Preterm Delivery, run by Nantes University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: difficulty of recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Venous umbilical cord blood concentration of glutathione (micromoles/L) following antenatal NAC supplementation. (time frame: 13 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2022.