Antenatal Melatonin Supplementation for Neuroprotection in Fetal Growth Restriction
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexFemale
Age18+
SponsorMonash University
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Singleton Pregnancy
Abdominal circumference ≤3rd centile for gestational age according to charts supplied that have been adapted from Westerway et al; or
Uterine artery (raised pulsatility index ≥95th centile)
Umbilical artery (pulsatility index ≥95th centile or absent/reversed end-diastolic flow)
Disqualifiers
A fetus with a known chromosomal, major structural anomaly or non-placental cause of fetal growth restriction
Pregnancies requiring immediate delivery (e.g. absent A wave in ductus venosus, preterminal CTG or biophysical profile)
Co-recruitment in another clinical trial where a pharmaceutical product or nutritional supplement impacting on oxidative stress is the trial intervention.
Currently prescribed Fluvoxamine
Trial design
Design model
Parallel
Treatments tested in this trial
Placebo
Other interventionTablets, visually identical to the melatonin tablets, but containing no active ingredient are administered three times a day.
Melatonin 10 MG
DrugMelatonin 10 mg tablets will be administered three times a day, up to a maximum of 30 mg daily
Treatment groups
336 Participants
are divided into 2 treatment groupsGroup A: PlaceboPlacebo comparator 1 intervention
Group B: MelatoninActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Neurodevelopmental performance at 2 years of life among survivors of early onset FGR.
The primary outcome will be identified by a change in the Bayley-IV Cognitive score of 5 or more points.
Time frame
24-36 months corrected ageSecondary outcomes
1
Incidence of patient reported side effects and adverse events with melatonin use in pregnancy
Maternal side effect profiles experienced, such as symptoms of abdominal cramps, flushing, migraines, gastrointestinal disturbance. This will be collected from the patient medication diary completed during treatment with reported side effects expressed as incidence (% patients).
Time frame
From randomisation until cessation of trial medication at birth, assessed for up to 18 weeks.2
Incidence of patient reported daytime somnolence with melatonin use in pregnancy
Maternal symptoms of drowsiness, obtained from the patient completed medication diary, will be expressed as an average somnolence score (scale 1-10).
Time frame
From randomisation until cessation of trial medication at birth, assessed for up to 18 weeks.3
Rate of altered maternal end-organ performance with melatonin supplementation
Haematological and biochemical investigations undertaken pre- and post- commencement of trial medication will be used to assess the rate of change in maternal end-organ function, particularly renal and liver function.
Time frame
Pre-intervention until 2 weeks post-commencement of intervention4
Impact of melatonin on fetal growth
The antenatal use of melatonin on estimated fetal growth (grams) will be assessed using ultrasound biometry parameters performed fortnightly following trial recruitment until birth. The fetal growth trajectory across gestation will be compared to the placebo group.
Time frame
From randomisation until birth, for up to 17 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
Monash University
Lead sponsor
National Health and Medical Research Council, Australia
Collaborator
Cerebral Palsy Alliance
Collaborator
Equity Trustees
Collaborator
Source ClinicalTrials.gov