Antenatal Melatonin Supplementation for Neuroprotection in Fetal Growth Restriction

NCT05651347 | Recruiting Phase 3 DMC

• 1 other identifier: U1111-1203-6718
• Study Type: interventional
• Target: 336
• Locations: 2 countries
• Sites: 12

Brief Summary

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.

Conditions

Fetal Growth Retardation; Stillbirth and Fetal Death; Pregnancy Preterm

Outcome Measures

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.

  24-36 months corrected age

Secondary Outcomes (5)

• Incidence of patient reported side effects and adverse events with melatonin use in pregnancy

  From randomisation until cessation of trial medication at birth, assessed for up to 18 weeks.

• Incidence of patient reported daytime somnolence with melatonin use in pregnancy

  From randomisation until cessation of trial medication at birth, assessed for up to 18 weeks.

• Rate of altered maternal end-organ performance with melatonin supplementation

  Pre-intervention until 2 weeks post-commencement of intervention

• Impact of melatonin on fetal growth

  From randomisation until birth, for up to 17 weeks

• Impact of melatonin on fetoplacental Dopplers

  From randomisation until birth, assessed for up to 17 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Visually identical placebo tablets containing no active ingredient to the active treatment, administered three times a day.

Other: Placebo

Melatonin

ACTIVE COMPARATOR

10mg Melatonin tablets, administered three times a day (a total daily dose of 30mg per day)

Drug: Melatonin 10 MG

Interventions

Placebo OTHER

Tablets, visually identical to the melatonin tablets, but containing no active ingredient are administered three times a day.

Placebo

Melatonin 10 MG DRUG

Melatonin 10 mg tablets will be administered three times a day, up to a maximum of 30 mg daily

Melatonin

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Singleton Pregnancy
• 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)
• Confirmed 23+0 - 31+6 weeks' gestation
• Age ≥18 years
• Understand English

You may not qualify if:

• 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

Sponsors & Collaborators

• Monash University: lead
• National Health and Medical Research Council, Australia: collaborator
• Cerebral Palsy Alliance: collaborator
• Equity Trustees: collaborator

Study Sites (12)

Royal Prince Alfred

Camperdown, New South Wales, 2050, Australia

RECRUITING

John Hunter Hospital

Newcastle, New South Wales, 2305, Australia

RECRUITING

Mater Misericordiae

South Brisbane, Queensland, 4101, Australia

RECRUITING

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

RECRUITING

Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

RECRUITING

Monash Health

Clayton, Victoria, 3168, Australia

RECRUITING

Mercy Hospital

Heidelberg, Victoria, 3084, Australia

RECRUITING

Royal Women's Hospital

Parkville, Victoria, 3052, Australia

RECRUITING

Joan Kirner Hospital

Saint Albans, Victoria, 3021, Australia

RECRUITING

Auckland Hospital

Auckland, 1023, New Zealand

RECRUITING

Middlemore Hospital

Auckland, 2025, New Zealand

RECRUITING

Wellington Regional Hospital

Wellington, 6021, New Zealand

RECRUITING

Related Publications (1)

• 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.

  PMID: 31230020 BACKGROUND

MeSH Terms

Conditions

Fetal Growth Retardation; Stillbirth; Fetal Death

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Death

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Kirsten Palmer, PhD

  Monash University & Monash Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kirsten Palmer, PhD

CONTACT

+61 3 9594 5145; kirsten.palmer@monash.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Triple-blinded, parallel group, placebo controlled trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: PROTECT Me aims to be a multicentre, triple-blinded, randomized, parallel group, placebo controlled trial

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: December 15, 2022
• Study Start: May 29, 2019
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: June 6, 2025

Record last verified: 2025-06

Locations

AU (9); NZ (3)