A randomised controlled trial of antenatal melatonin supplementation in fetal growth restriction for fetal neuroprotection.

A triple-blind, randomized, parallel-group, placebo controlled trial to assess the impact of maternal antenatal melatonin supplementation on early childhood neurodevelopmental outcomes in the setting of severe preterm fetal growth restriction.

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12617001515381

Acronym

The Protect Me Trial

Enrollment

338

Registered

2017-10-30

Start date

2019-05-30

Completion date

2025-01-30

Last updated

2026-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

During pregnancy, fetal growth restriction (FGR) is a recognised causal pathway to neurodevelopmental injury, which manifests, following birth, as cognitive and behavioural impairment as well as cerebral palsy. Currently, antenatal care is focused on detecting FGR and assessment of fetal wellbeing to guide timing of delivery. This approach seeks to maximize gestational age at birth to minimise the risks of prematurity, while delivering the fetus in time to minimise the likelihood of stillbirth. However, no therapies exist that can maximize fetal wellbeing in the setting of FGR and minimise the frequency of antenatally acquired brain injury. This double-blind RCT seeks to recruit n=332 women with FGR pregnancies to determine if antenatal maternal Melatonin administration can PROTECT the fetal brain and lead to improved neurodevelopmental outcomes.

Interventions

The intervention for this trial is: melatonin (10mg) -the dose administered, 10mg three times daily (tds) - the duration of administration: from the time of recruitment to the trial until birth - the mode of administration: oral tablet

Study design

Allocation

Randomised controlled trial

Intervention model

Parallel

Primary purpose

Prevention

Masking

Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1) Women, with a singleton pregnancy 2) Severe fetal growth restriction (FGR), defined as: Estimated fetal weight equal to, or less than, 3rd centile for gestational age according to charts from Mikolajczyk et al (2011) or an estimated fetal weight that is less than the 10th centile (Mikolajcyk et al 2011) in combination with at least one abnormal fetoplacental doppler study, these being: - Uterine artery (raised pulsatility index equal to, or more than, 95th centile) - Umbilical artery (pulsatility index equal to, or more than, 95th centile or absent/reversed end-diastolic flow) - Ductus venosus (abnormal A wave and/or pulsatility index equal to, or more than, 95th centile) 3) Gestation: (confirmed) 23+0 to 31+6 weeks’ 4) Age: 18 years or more 5) Understands English Reference: Mikolajczyk, R.T., et al., A global reference for fetal-weight and birthweight percentiles. Lancet, 2011. 377 (9780): pp. 1855-61

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 (eg 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 is the trial intervention.

Outcome results