Antenatal Melatonin Supplementation for Neuroprotection in Fetal Growth Restriction
NCT ID: NCT05651347
Last Updated: 2025-06-06
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
RECRUITING
Clinical Phase
PHASE3
Total Enrollment
336 participants
Study Classification
INTERVENTIONAL
Study Start Date
2019-05-29
Study Completion Date
2027-04-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Fetal growth restriction (FGR) is a significant health care issue, affecting 20,000 Australian pregnancies every year. Undetected FGR is one of the key risk factors for stillbirth, but FGR can also cause significant impairments in short and long-term health outcomes for the child.
It is a major risk factor for preterm birth and is a recognised causal pathway to the neurodevelopmental injury underlying cognitive and behavioural impairment and cerebral palsy. Current obstetric care is focused on the detection of the growth restricted fetus and then ultrasound assessment of fetal wellbeing to guide timing of delivery. This approach seeks to maximize the gestational age of the fetus at delivery to minimise the risks of prematurity, while delivering the fetus in time to reduce the likelihood of stillbirth. Currently, no therapies exist that can maximize fetal wellbeing in the setting of growth restriction and minimise the frequency of antenatally acquired brain injury due to in-utero hypoxia.
This triple-blind, randomized, parallel group, placebo-controlled trial will administer maternal melatonin or placebo supplementation antenatally in the setting of early-onset severe FGR to determine whether melatonin can PROTECT the fetal brain and lead to improved neurodevelopmental outcomes.
It is a major risk factor for preterm birth and is a recognised causal pathway to the neurodevelopmental injury underlying cognitive and behavioural impairment and cerebral palsy. Current obstetric care is focused on the detection of the growth restricted fetus and then ultrasound assessment of fetal wellbeing to guide timing of delivery. This approach seeks to maximize the gestational age of the fetus at delivery to minimise the risks of prematurity, while delivering the fetus in time to reduce the likelihood of stillbirth. Currently, no therapies exist that can maximize fetal wellbeing in the setting of growth restriction and minimise the frequency of antenatally acquired brain injury due to in-utero hypoxia.
This triple-blind, randomized, parallel group, placebo-controlled trial will administer maternal melatonin or placebo supplementation antenatally in the setting of early-onset severe FGR to determine whether melatonin can PROTECT the fetal brain and lead to improved neurodevelopmental outcomes.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
The Use of Gastrografin to Help Alleviate Bowel Obstruction in Gastroschisis Patients.
NCT03334578
Gastroschisis
Bowel Obstruction
Birth Defect
WITHDRAWN
PHASE4
Maternal B12 Supplementation to Improve Infant B12 Deficiency and Neurodevelopment
NCT03783104
Child Developmental Delay
Child Malnutrition
Maternal Exposure
+1 more
UNKNOWN
NA
Oral Melatonin as Neuroprotectant in Preterm Infants
NCT04235673
Malondialdehyde
Melatonin
COMPLETED
NA
Use of Prokinetics in Early Enteral Feeding in Preterm Infants
NCT01569633
Feeding Disorder
Nutrition Disorder
Infant,Premature
WITHDRAWN
NA
Pharmacokinetics of Melatonin Niosomes Oral Gel in Healthy Volunteers
NCT02845778
Pharmacokinetics of Melatonin
UNKNOWN
PHASE1/PHASE2
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Following detection of FGR, current goals in clinical care center on assessment of fetal wellbeing and evidence of a physiological adaption to placental insufficiency. This information guides the timing of steroids, if indicated, and planning of delivery to minimise the likelihood of stillbirth. Magnesium sulphate is the only available therapy shown to improve fetal brain development in the setting of placental insufficiency and hypoxia. Magnesium sulphate works through reducing glutamate release in a hypoxic environment, likely minimising hypoxic brain injury. It appears to reduce the risk of subsequent cerebral palsy by approximately 30%. However, magnesium sulphate is only used in the hours immediately before birth, while a significant proportion of underlying brain injury in FGR probably occurs over the preceding days to weeks. The use of a safe, maternally administered supplement commenced in the weeks prior to birth could provide further significant benefits in reducing the complications faced by premature infants in the setting of placental insufficiency.
Melatonin (5-methoxy-N-acetyltryptamine) is an endogenous lipid-soluble hormone produced primarily by the pineal gland in humans. It provides circadian and seasonal timing cues due to neuroendocrine control in response to daylight. As such, melatonin secretion is relatively low during the daytime, with an exponential increase in synthesis and secretion occurring from mid-afternoon and peaking at midnight.
In addition to timing cues, melatonin is a powerful antioxidant, acting both as a direct scavenger of oxygen free radicals, especially the highly damaging hydroxyl radical, and indirectly via up-regulation of antioxidant enzymes including glutathione peroxidase, glutathione-reductase, superoxide dismutase and catalase. The metabolites of melatonin provide further anti-oxidant effect.
Melatonin is an appealing treatment for use as a fetal neuroprotectant in pregnancy, as it freely crosses the placenta and blood-brain barrier. It also has an excellent safety profile with no known adverse effects. Placentae express receptors for melatonin, and thus melatonin may protect against oxidative stress generated by ischaemia-reperfusion injury of the placenta.
Melatonin has been studied in several clinical trials related to human reproduction and for different purposes. However, no randomized trial assessing the role of melatonin in fetal neuroprotection has been completed. Melatonin has been evaluated in assisted reproductive technology where the quality of oocytes is vital for the success of in-vitro fertilization (IVF). Melatonin and myo-inositol are two compounds found in the follicular fluid that are important for oocyte maturation and quality. Tamura et al. (in 2008) and Rizzo et al. (in 2010) conducted clinical studies where they co-treated patients with 2milligram (mg) and 3mg melatonin respectively. The patients in the Tamura et al. study were given melatonin from the fifth day of the previous menstrual cycle until the day of oocyte retrieval. Both studies revealed improved oocyte quality, but the tendency to increase pregnancy rates failed to reach statistical significance. A study conducted by Unfer et al. in 2011 administered 2g myo-inositol, 200µg folic acid plus 3mg melatonin per day for 3-months to women who failed to become pregnant in previous IVF cycles, at the commencement of a new IVF cycle. This treatment resulted in a total of 13 pregnancies, 9 of which were confirmed ultrasonographically and 4 undergoing spontaneous abortion. Treatment continued after completion of the IVF cycle, throughout pregnancy until delivery. Treatment was associated with better quality oocytes and more successful pregnancies. All babies that were born from melatonin-treated pregnancies were in healthy condition with no abnormalities.
To evaluate the maternal-fetal transfer of melatonin a study by Okatani et al. in 1998 administered a single oral dose of 3mg melatonin to 33 women at term (37-40 weeks gestation) 1- to 4-hours before a planned caesarean section. Levels of melatonin were evaluated in maternal venous blood and umbilical venous and arterial blood. A total of 12 healthy pregnant women delivered by vaginal birth served as controls. Administration of melatonin led to a rapid (\<120 minutes) and marked (\>20-fold) increase in the fetal serum levels. There were no differences between maternal and fetal serum levels of melatonin, suggesting a rapid and unrestricted transfer of melatonin from mother to fetus.
The same investigators tested whether melatonin could up-regulate antioxidant enzymes. No longer than 12 hours before voluntary termination of pregnancy (between 7- and 9-weeks gestation), an oral dose of 6mg melatonin was administered to 47 pregnant women. A significant increase of the antioxidant enzyme glutathione peroxidase was observed in chorionic homogenates derived after the procedure, leading to the conclusion that melatonin might provide an indirect protection against injury caused by reactive oxygen species as seen in preeclampsia, FGR and fetal hypoxia.
The dose used in this trial is based on data from a clinical trial of melatonin for preeclampsia showing that 30mg per day was safe for mother and baby without any apparent adverse effects. Venous cord blood concentrations of melatonin achieved were unchanged between a mother receiving 8mg and 30mg per day of melatonin (melatonin concentration \~2100pg/mL). This cord blood concentration would appear sufficient for neuroprotection according to information in sheep models. However, the degree of oxidative stress reduction achieved within the placental bed was less in mothers receiving 8mg melatonin per day. As such, it was felt that the higher dose of 30mg per day was more likely to achieve a clinically significant result.
The investigating team has shown that melatonin supplementation exerts multiple anti-oxidant and anti-inflammatory effects, leading to a significant reduction in oxidative stress and lipid peroxidation within the fetal brain in an ovine model of FGR. In the absence of melatonin, this study showed that lipid peroxidation within the fetal brain led to significant white matter hypomyelination and axonal injury, causing impaired neurological performance in the lambs. Injury was ameliorated entirely in those exposed to melatonin supplementation, with no structural brain injury seen and neurodevelopmental outcomes normalised.
As a result, a small (n=12) phase 1 trial was conducted at Monash Health supplementing pregnancies affected by severe FGR with 8mg of melatonin per day. Melatonin use was well tolerated with no adverse effects seen. A reduction in the degree of placental lipid peroxidation was seen (n=6).
Early-onset FGR carries significant fetal risks of premature birth. Following diagnosis, those babies requiring delivery \<32 weeks gestation carry approximately an 8% risk of stillbirth or neonatal death, with those born \<28 weeks gestation having a significantly higher perinatal mortality rate. Around 30% of survivors will suffer serious neonatal morbidity. Furthermore, 8% are found to have neurodevelopmental impairment at two years of life. These numbers are likely to be an underrepresentation as they are from a trial population, which was closely surveyed compared to the general population.
With approximately 97% of FGR infants born \<32 weeks delivered by caesarean section, the mother of a preterm FGR fetus faces the risks associated with morbidity and mortality relating to caesarean birth. Furthermore, the mother also faces a significant risk of morbidity and mortality from pre-eclampsia, which develops among 15 - 40% of women who have a growth-restricted fetus.
The most common side effects of melatonin are headache, dizziness, nausea and sleepiness. Melatonin does not have any acute pharmacological effects on the nervous or vascular systems, apart from its benign but active impact on sleep mechanisms. Extremely high doses of up to 800mg/kg of melatonin were safely administered to animals without deaths, meaning a median lethal dose could not be established. In humans, long-term treatment with high, daily doses of up to 10g melatonin did not cause any toxicity except for isolated cases of cutaneous flushing, abdominal cramps, diarrhoea, scotoma lucidum and migraine.
Prolonged ingestion of 1g melatonin per day caused only subjective drowsiness but did not provoke any toxicity in the eyes, liver, kidneys and bone marrow. In a phase II clinical trial conducted in the Netherlands, 1400 women were given 75mg melatonin nightly over 4-years, with no side effects reported.
The safety of melatonin use in pregnancy was explored in early pregnant Sprague-Dawley rats, at doses ranging from 1 to 200mg/kg/day and did not affect antenatal mortality, fetal body weight or other measures of fetal wellbeing. Maternal adverse effects seen at high doses, included mild sedation, reduced maternal weight gain and reduced food intake. This study sought to determine the maternal and fetal no adverse effect level (NOAEL). The NOAEL is the exposure level where a particular substance does not statistically or biologically significantly increase the frequency or severity of adverse effects in an exposed population compared to a suitable control population. The maternal NOAEL in this study was found to be 100mg/kg/day, the fetal NOAEL was established at ≥200mg/kg/day when administered to the mother. The maternal lowest observed adverse effect level toxicity was 200mg/kg/day. With the above information taken in context, the Australian Therapeutic Goods Administration (TGA) has assigned melatonin a Pregnancy Category B3 classification.
The investigators have recently completed a phase 1 trial (NCT01695070) using melatonin supplementation in pregnancy, as well as a clinical trial in women with pre-eclampsia (ACTRN12613000476730) using the same dose as proposed for this trial, and to date no adverse effects have been identified in the mother, fetus or neonate.
PROTECT Me aims to be a multicentre, triple-blinded, randomized, parallel group, placebo controlled trial. This trial will be undertaken and co-ordinated by Monash Health.
Other perinatal hospitals across Australia and New Zealand have agreed to join the trial so far. Each centre will nominate a local investigator +/- a researcher to oversee local recruitment.
The required sample size has been calculated to detect if melatonin supplementation affords a clinically relevant difference in neurodevelopmental outcomes among survivors. An increase of 4-5 quotient points in the Bayley-IV Cognitive scale has been deemed sufficiently clinically meaningful to drive changes in health policy previously. Power analysis shows that 69 participants per group will allow the detection of a difference in the Bayley-IV cognitive score of 5 points between the two groups, with a power of 90% and an alpha level of 0.05, using 2 sided T test for comparison. This assumes a standard deviation of 9 and that, on average, the growth restricted infant has been shown to have a cognitive score 5 points lower than the healthy preterm infant and 8 points lower than the healthy term infant. Typically, the Bayley IV score has a standard deviation of 15, however reduced variability has been seen in the FGR population and this has informed the standard deviation used here. Among pregnancies complicated by early onset FGR a perinatal loss rate of \~15% is commonly observed. Allowing for a perinatal loss rate of 15%, an extra 44 women will be recruited. Assuming an additional 5% loss to follow-up rate, the investigators will aim to recruit an extra 14 participants.
This trial also aims to assess whether the impact of melatonin is different at different gestational ages. Therefore, a sub-analysis will be undertaken to compare those with early onset FGR identified \<28 weeks' gestation to those with late-onset FGR identified between 28-31+6 weeks gestation. To ensure that this sub-analysis is adequately powered, participants recruited will be randomized to either melatonin or placebo based on their gestational age at diagnosis. Therefore, recruiting 84 participants per group will see the overall trial aiming to recruit 336 participants.
Melatonin (5-methoxy-N-acetyltryptamine) is an endogenous lipid-soluble hormone produced primarily by the pineal gland in humans. It provides circadian and seasonal timing cues due to neuroendocrine control in response to daylight. As such, melatonin secretion is relatively low during the daytime, with an exponential increase in synthesis and secretion occurring from mid-afternoon and peaking at midnight.
In addition to timing cues, melatonin is a powerful antioxidant, acting both as a direct scavenger of oxygen free radicals, especially the highly damaging hydroxyl radical, and indirectly via up-regulation of antioxidant enzymes including glutathione peroxidase, glutathione-reductase, superoxide dismutase and catalase. The metabolites of melatonin provide further anti-oxidant effect.
Melatonin is an appealing treatment for use as a fetal neuroprotectant in pregnancy, as it freely crosses the placenta and blood-brain barrier. It also has an excellent safety profile with no known adverse effects. Placentae express receptors for melatonin, and thus melatonin may protect against oxidative stress generated by ischaemia-reperfusion injury of the placenta.
Melatonin has been studied in several clinical trials related to human reproduction and for different purposes. However, no randomized trial assessing the role of melatonin in fetal neuroprotection has been completed. Melatonin has been evaluated in assisted reproductive technology where the quality of oocytes is vital for the success of in-vitro fertilization (IVF). Melatonin and myo-inositol are two compounds found in the follicular fluid that are important for oocyte maturation and quality. Tamura et al. (in 2008) and Rizzo et al. (in 2010) conducted clinical studies where they co-treated patients with 2milligram (mg) and 3mg melatonin respectively. The patients in the Tamura et al. study were given melatonin from the fifth day of the previous menstrual cycle until the day of oocyte retrieval. Both studies revealed improved oocyte quality, but the tendency to increase pregnancy rates failed to reach statistical significance. A study conducted by Unfer et al. in 2011 administered 2g myo-inositol, 200µg folic acid plus 3mg melatonin per day for 3-months to women who failed to become pregnant in previous IVF cycles, at the commencement of a new IVF cycle. This treatment resulted in a total of 13 pregnancies, 9 of which were confirmed ultrasonographically and 4 undergoing spontaneous abortion. Treatment continued after completion of the IVF cycle, throughout pregnancy until delivery. Treatment was associated with better quality oocytes and more successful pregnancies. All babies that were born from melatonin-treated pregnancies were in healthy condition with no abnormalities.
To evaluate the maternal-fetal transfer of melatonin a study by Okatani et al. in 1998 administered a single oral dose of 3mg melatonin to 33 women at term (37-40 weeks gestation) 1- to 4-hours before a planned caesarean section. Levels of melatonin were evaluated in maternal venous blood and umbilical venous and arterial blood. A total of 12 healthy pregnant women delivered by vaginal birth served as controls. Administration of melatonin led to a rapid (\<120 minutes) and marked (\>20-fold) increase in the fetal serum levels. There were no differences between maternal and fetal serum levels of melatonin, suggesting a rapid and unrestricted transfer of melatonin from mother to fetus.
The same investigators tested whether melatonin could up-regulate antioxidant enzymes. No longer than 12 hours before voluntary termination of pregnancy (between 7- and 9-weeks gestation), an oral dose of 6mg melatonin was administered to 47 pregnant women. A significant increase of the antioxidant enzyme glutathione peroxidase was observed in chorionic homogenates derived after the procedure, leading to the conclusion that melatonin might provide an indirect protection against injury caused by reactive oxygen species as seen in preeclampsia, FGR and fetal hypoxia.
The dose used in this trial is based on data from a clinical trial of melatonin for preeclampsia showing that 30mg per day was safe for mother and baby without any apparent adverse effects. Venous cord blood concentrations of melatonin achieved were unchanged between a mother receiving 8mg and 30mg per day of melatonin (melatonin concentration \~2100pg/mL). This cord blood concentration would appear sufficient for neuroprotection according to information in sheep models. However, the degree of oxidative stress reduction achieved within the placental bed was less in mothers receiving 8mg melatonin per day. As such, it was felt that the higher dose of 30mg per day was more likely to achieve a clinically significant result.
The investigating team has shown that melatonin supplementation exerts multiple anti-oxidant and anti-inflammatory effects, leading to a significant reduction in oxidative stress and lipid peroxidation within the fetal brain in an ovine model of FGR. In the absence of melatonin, this study showed that lipid peroxidation within the fetal brain led to significant white matter hypomyelination and axonal injury, causing impaired neurological performance in the lambs. Injury was ameliorated entirely in those exposed to melatonin supplementation, with no structural brain injury seen and neurodevelopmental outcomes normalised.
As a result, a small (n=12) phase 1 trial was conducted at Monash Health supplementing pregnancies affected by severe FGR with 8mg of melatonin per day. Melatonin use was well tolerated with no adverse effects seen. A reduction in the degree of placental lipid peroxidation was seen (n=6).
Early-onset FGR carries significant fetal risks of premature birth. Following diagnosis, those babies requiring delivery \<32 weeks gestation carry approximately an 8% risk of stillbirth or neonatal death, with those born \<28 weeks gestation having a significantly higher perinatal mortality rate. Around 30% of survivors will suffer serious neonatal morbidity. Furthermore, 8% are found to have neurodevelopmental impairment at two years of life. These numbers are likely to be an underrepresentation as they are from a trial population, which was closely surveyed compared to the general population.
With approximately 97% of FGR infants born \<32 weeks delivered by caesarean section, the mother of a preterm FGR fetus faces the risks associated with morbidity and mortality relating to caesarean birth. Furthermore, the mother also faces a significant risk of morbidity and mortality from pre-eclampsia, which develops among 15 - 40% of women who have a growth-restricted fetus.
The most common side effects of melatonin are headache, dizziness, nausea and sleepiness. Melatonin does not have any acute pharmacological effects on the nervous or vascular systems, apart from its benign but active impact on sleep mechanisms. Extremely high doses of up to 800mg/kg of melatonin were safely administered to animals without deaths, meaning a median lethal dose could not be established. In humans, long-term treatment with high, daily doses of up to 10g melatonin did not cause any toxicity except for isolated cases of cutaneous flushing, abdominal cramps, diarrhoea, scotoma lucidum and migraine.
Prolonged ingestion of 1g melatonin per day caused only subjective drowsiness but did not provoke any toxicity in the eyes, liver, kidneys and bone marrow. In a phase II clinical trial conducted in the Netherlands, 1400 women were given 75mg melatonin nightly over 4-years, with no side effects reported.
The safety of melatonin use in pregnancy was explored in early pregnant Sprague-Dawley rats, at doses ranging from 1 to 200mg/kg/day and did not affect antenatal mortality, fetal body weight or other measures of fetal wellbeing. Maternal adverse effects seen at high doses, included mild sedation, reduced maternal weight gain and reduced food intake. This study sought to determine the maternal and fetal no adverse effect level (NOAEL). The NOAEL is the exposure level where a particular substance does not statistically or biologically significantly increase the frequency or severity of adverse effects in an exposed population compared to a suitable control population. The maternal NOAEL in this study was found to be 100mg/kg/day, the fetal NOAEL was established at ≥200mg/kg/day when administered to the mother. The maternal lowest observed adverse effect level toxicity was 200mg/kg/day. With the above information taken in context, the Australian Therapeutic Goods Administration (TGA) has assigned melatonin a Pregnancy Category B3 classification.
The investigators have recently completed a phase 1 trial (NCT01695070) using melatonin supplementation in pregnancy, as well as a clinical trial in women with pre-eclampsia (ACTRN12613000476730) using the same dose as proposed for this trial, and to date no adverse effects have been identified in the mother, fetus or neonate.
PROTECT Me aims to be a multicentre, triple-blinded, randomized, parallel group, placebo controlled trial. This trial will be undertaken and co-ordinated by Monash Health.
Other perinatal hospitals across Australia and New Zealand have agreed to join the trial so far. Each centre will nominate a local investigator +/- a researcher to oversee local recruitment.
The required sample size has been calculated to detect if melatonin supplementation affords a clinically relevant difference in neurodevelopmental outcomes among survivors. An increase of 4-5 quotient points in the Bayley-IV Cognitive scale has been deemed sufficiently clinically meaningful to drive changes in health policy previously. Power analysis shows that 69 participants per group will allow the detection of a difference in the Bayley-IV cognitive score of 5 points between the two groups, with a power of 90% and an alpha level of 0.05, using 2 sided T test for comparison. This assumes a standard deviation of 9 and that, on average, the growth restricted infant has been shown to have a cognitive score 5 points lower than the healthy preterm infant and 8 points lower than the healthy term infant. Typically, the Bayley IV score has a standard deviation of 15, however reduced variability has been seen in the FGR population and this has informed the standard deviation used here. Among pregnancies complicated by early onset FGR a perinatal loss rate of \~15% is commonly observed. Allowing for a perinatal loss rate of 15%, an extra 44 women will be recruited. Assuming an additional 5% loss to follow-up rate, the investigators will aim to recruit an extra 14 participants.
This trial also aims to assess whether the impact of melatonin is different at different gestational ages. Therefore, a sub-analysis will be undertaken to compare those with early onset FGR identified \<28 weeks' gestation to those with late-onset FGR identified between 28-31+6 weeks gestation. To ensure that this sub-analysis is adequately powered, participants recruited will be randomized to either melatonin or placebo based on their gestational age at diagnosis. Therefore, recruiting 84 participants per group will see the overall trial aiming to recruit 336 participants.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Fetal Growth Retardation
Stillbirth and Fetal Death
Pregnancy Preterm
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
PROTECT Me aims to be a multicentre, triple-blinded, randomized, parallel group, placebo controlled trial
Primary Study Purpose
TREATMENT
Blinding Strategy
QUADRUPLE
Participants
Caregivers
Investigators
Outcome Assessors
Triple-blinded, parallel group, placebo controlled trial
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Placebo
Visually identical placebo tablets containing no active ingredient to the active treatment, administered three times a day.
Group Type
PLACEBO_COMPARATOR
Placebo
Intervention Type
OTHER
Tablets, visually identical to the melatonin tablets, but containing no active ingredient are administered three times a day.
Melatonin
10mg Melatonin tablets, administered three times a day (a total daily dose of 30mg per day)
Group Type
ACTIVE_COMPARATOR
Melatonin 10 MG
Intervention Type
DRUG
Melatonin 10 mg tablets will be administered three times a day, up to a maximum of 30 mg daily
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Placebo
Tablets, visually identical to the melatonin tablets, but containing no active ingredient are administered three times a day.
Intervention Type
OTHER
Melatonin 10 MG
Melatonin 10 mg tablets will be administered three times a day, up to a maximum of 30 mg daily
Intervention Type
DRUG
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. Singleton Pregnancy
2. Severe fetal growth restriction, defined as:
* Abdominal circumference ≤3rd centile for gestational age according to charts supplied that have been adapted from Westerway et al; or
* Abdominal circumference \<10th centile in combination with at least one abnormal fetoplacental Doppler study, being:
* Uterine artery (raised pulsatility index ≥95th centile)
* Umbilical artery (pulsatility index ≥95th centile or absent/reversed end-diastolic flow)
3. Confirmed 23+0 - 31+6 weeks' gestation
4. Age ≥18 years
5. Understand English
2. Severe fetal growth restriction, defined as:
* Abdominal circumference ≤3rd centile for gestational age according to charts supplied that have been adapted from Westerway et al; or
* Abdominal circumference \<10th centile in combination with at least one abnormal fetoplacental Doppler study, being:
* Uterine artery (raised pulsatility index ≥95th centile)
* Umbilical artery (pulsatility index ≥95th centile or absent/reversed end-diastolic flow)
3. Confirmed 23+0 - 31+6 weeks' gestation
4. Age ≥18 years
5. Understand English
Exclusion Criteria
1. A fetus with a known chromosomal, major structural anomaly or non-placental cause of fetal growth restriction
2. Pregnancies requiring immediate delivery (e.g. absent A wave in ductus venosus, preterminal CTG or biophysical profile)
3. Co-recruitment in another clinical trial where a pharmaceutical product or nutritional supplement impacting on oxidative stress is the trial intervention.
4. Currently prescribed Fluvoxamine
2. Pregnancies requiring immediate delivery (e.g. absent A wave in ductus venosus, preterminal CTG or biophysical profile)
3. Co-recruitment in another clinical trial where a pharmaceutical product or nutritional supplement impacting on oxidative stress is the trial intervention.
4. Currently prescribed Fluvoxamine
Minimum Eligible Age
18 Years
Eligible Sex
FEMALE
Accepts Healthy Volunteers
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Health and Medical Research Council, Australia
OTHER
Sponsor Role
collaborator
Cerebral Palsy Alliance
OTHER
Sponsor Role
collaborator
Equity Trustees
UNKNOWN
Sponsor Role
collaborator
Monash University
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Dr Kirsten R. Palmer
Principal Investigator
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Kirsten Palmer, PhD
Role: PRINCIPAL_INVESTIGATOR
Monash University & Monash Health
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Royal Prince Alfred
Camperdown, New South Wales, Australia
Site Status
RECRUITING
John Hunter Hospital
Newcastle, New South Wales, Australia
Site Status
RECRUITING
Mater Misericordiae
South Brisbane, Queensland, Australia
Site Status
RECRUITING
Gold Coast University Hospital
Southport, Queensland, Australia
Site Status
RECRUITING
Women's and Children's Hospital
North Adelaide, South Australia, Australia
Site Status
RECRUITING
Monash Health
Clayton, Victoria, Australia
Site Status
RECRUITING
Mercy Hospital
Heidelberg, Victoria, Australia
Site Status
RECRUITING
Royal Women's Hospital
Parkville, Victoria, Australia
Site Status
RECRUITING
Joan Kirner Hospital
Saint Albans, Victoria, Australia
Site Status
RECRUITING
Auckland Hospital
Auckland, , New Zealand
Site Status
RECRUITING
Middlemore Hospital
Auckland, , New Zealand
Site Status
RECRUITING
Wellington Regional Hospital
Wellington, , New Zealand
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
Australia
New Zealand
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Bronni Simpson, PhD
Role: backup
+61 478 257 621
References
Explore related publications, articles, or registry entries linked to this study.
Palmer KR, Mockler JC, Davies-Tuck ML, Miller SL, Goergen SK, Fahey MC, Anderson PJ, Groom KM, Wallace EM. Protect-me: a parallel-group, triple blinded, placebo-controlled randomised clinical trial protocol assessing antenatal maternal melatonin supplementation for fetal neuroprotection in early-onset fetal growth restriction. BMJ Open. 2019 Jun 22;9(6):e028243. doi: 10.1136/bmjopen-2018-028243.
Reference Type
BACKGROUND
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
U1111-1203-6718
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Efficacy of Combination Therapy vs Placebo for Pediatric Functional Abdominal Pain
NCT01269671
WITHDRAWN
PHASE1
Melatonin CR for the Treatment of Impaired Sleep Maintenance in 4-8 Year Old Children With Autism Spectrum Disorders
NCT01033565
TERMINATED
PHASE4
Postnatal Choline Supplementation in Children With Prenatal Alcohol Exposure
NCT01149538
COMPLETED
PHASE1/PHASE2
Copeptin for Prediction of Treatment Response in Children With Monosymptomatic Nocturnal Enuresis (MEN).
NCT02621736
COMPLETED
Pilot Study of the Effects of the Desipramine on the Neurovegetative Parameters of the Child With Rett Syndrome
NCT00990691
COMPLETED
PHASE2
Effects of Fat-soluble Vitamins Supplementation on Common Complications and Neural Development in Very Low Birth Weight Infants
NCT03876704
UNKNOWN
PHASE3
Use of Mometasone Eluting Stent in Choanal Atresia
NCT03605537
WITHDRAWN
PHASE4
Independent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome
NCT00069550
UNKNOWN
PHASE3
Single-Dose AAV-MECP2 Safety/Tolerability and Efficacy in Rett Syndrome
NCT06856759
RECRUITING
EARLY_PHASE1
Metoclopramide Pilot Trial
NCT02098915
TERMINATED
PHASE3
Electrogastrography (EGC) in Premature Infants With Feeding Intolerance
NCT00008736
COMPLETED
PHASE2
Open-Label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome
NCT04279314
COMPLETED
PHASE3
Enteral Zinc to Improve Growth in Infants at Risk for Bronchopulmonary Dysplasia
NCT03532555
TERMINATED
NA
Oral Vitamin A Supplementation in Neonates With Birth Weight < 1500 g
NCT02102711
COMPLETED
NA
Osteopathic Manipulative Treatment for Constipation in People With Rett Syndrome
NCT05687214
COMPLETED
NA
Intratracheal Vitamin A Administration With Surfactant for Newborn Respiratory Distress Syndrome
NCT01265589
UNKNOWN
PHASE3
Metoclopramide Use in Very Low Birth Weight Newborns
NCT00242450
COMPLETED
PHASE4
Effect of Vitamin A in the Treatment of Neonatal Sepsis and Necrotizing Enterocolitis
NCT00707785
COMPLETED
PHASE3
Open-Label Extension Study of Trofinetide for Rett Syndrome
NCT04776746
TERMINATED
PHASE3
Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03088189
TERMINATED
Effects of Cyproheptadine on Growth and Behavior in Pediatric Feeding Disorders
NCT02568007
TERMINATED
PHASE4
Vitamin A Supplementation in Preterm Infants
NCT00063596
UNKNOWN
NA
Effects of Creatine Supplementation in Rett Syndrome
NCT01147575
COMPLETED
NA
Melatonin Studies of Totally Blind Children
NCT00795236
TERMINATED
NA
Vitamin A and Very Low Birthweight Babies (VitAL)
NCT00417404
COMPLETED
PHASE4