Melatonin to Prevent Brain Injury in Unborn Growth Restricted Babies

NCT01695070 | Completed Phase 4

• 2 other identifiers: U1111-1133-4541ACTRN12612000858897
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Intrauterine growth restriction is the term used to describe a condition where an unborn baby does not reach its optimum size. In the short and long term, intrauterine growth restricted babies have a higher risk of serious disease and even death. It is well established that very low levels of oxygen in the baby's blood can harm the baby's health through a state known as oxidative stress. Currently, there is no established treatment available to treat intrauterine growth restriction or its complications. In experimental animal studies however, the naturally occuring hormone, melatonin, has been shown to significantly reduce oxidative stress and improve health of the unborn babies that have suffered from intrauterine growth restriction. This study aims to find out if the use melatonin twice per day throughout pregnancies affected by intrauterine growth restriction will lower the level of oxidative stress experienced by the unborn baby. If this is the case melatonin may help protect the unborn baby from damage caused by oxidative stress, this will be studied in a separate future study.

Conditions

Fetal Growth Retardation

Outcome Measures

Primary Outcomes (1)

• Oxidative stress in the umbilical artery

  Umbilical artery oxidative stress by measuring levels of malondialdehyde (MDA) and 8-isoprostane. Levels of MDA will be assessed using a Thiobarbituric Acid Reactive Substances Assay Kit (Cayman Chemical Item Number 10009055). Levels of 8-isoprostane will be assessed using an 8-Isoprostane Enzyme Immuno Assay Kit (Cayman Chemical Item Number 516351).

  Once, at birth.

Secondary Outcomes (5)

• Oxidative stress in maternal venous serum

  Once within one week before start treatment and once per week during the treatment period (estimated to be an average of 4 weeks).

• Fetoplacental Doppler studies

  Once within one week before start treatment and twice per week during the treatment period (estimated to be an average of 4 weeks).

• Placental oxidative stress

  Once, at birth.

• Gestational age at birth.

  Once, at birth.

• Composite neonatal outcome.

  Participants will be followed for the duration of hospital stay, up to 12 months.

Study Arms (1)

Melatonin

EXPERIMENTAL

Women with IUGR will take 4mg prolonged release melatonin oral tablets twice daily. Treatment will occur as soon as the diagnosis of intrauterine growth restriction is made and the patient has been enrolled to this study until birth. The overall duration of treatment will vary due to the nature of intrauterine growth restriction.

Drug: Melatonin

Interventions

Melatonin DRUG

4mg prolonged release melatonin oral tablets twice daily

Also known as: Circadin

Melatonin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Estimated fetal weight \<10th percentile in combination with abnormal fetoplacental Doppler studies.
• Singleton pregnancy.
• Live fetus.
• Gestational age: from 23+0 weeks until 34+0 weeks.
• Normal fetal anatomy on ultrasound.
• Confirmed gestational age.
• No indication for immediate delivery.
• Basic understanding of the English language.
• years or older.
• Consent obtained.

You may not qualify if:

• Fetal demise.
• Multiple pregnancy.
• Known abnormal karyotype.
• Presence of any congenital abnormality.
• Unknown duration of pregnancy.
• IUGR attributable to non-placental factors.

Sponsors & Collaborators

• Monash University: lead

Study Sites (1)

Southern Health: Monash Medical Centre and Jessie McPherson Private Hospital

Clayton, Victoria, 3168, Australia

Location

Related Publications (2)

• Miller SL, Yawno T, Alers NO, Castillo-Melendez M, Supramaniam VG, VanZyl N, Sabaretnam T, Loose JM, Drummond GR, Walker DW, Jenkin G, Wallace EM. Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury caused by fetal growth restriction. J Pineal Res. 2014 Apr;56(3):283-94. doi: 10.1111/jpi.12121. Epub 2014 Feb 22.

  PMID: 24456220 DERIVED

• Alers NO, Jenkin G, Miller SL, Wallace EM. Antenatal melatonin as an antioxidant in human pregnancies complicated by fetal growth restriction--a phase I pilot clinical trial: study protocol. BMJ Open. 2013 Dec 23;3(12):e004141. doi: 10.1136/bmjopen-2013-004141.

  PMID: 24366583 DERIVED

MeSH Terms

Conditions

Fetal Growth Retardation

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Nicole O Alers, MD

  The Ritchie Centre, Monash Institute of Medical Research, Monash University

  PRINCIPAL INVESTIGATOR

• Euan M Wallace, MBChB MD FRCOG FRANZCOG

  Southern Health, The Ritchie Centre, Monash Institute of Medical Research, Monash University

  PRINCIPAL INVESTIGATOR

• Graham Jenkin, BSc PhD

  The Ritchie Centre, Monash Institute of Medical Research

  PRINCIPAL INVESTIGATOR

• Suzanne L Miller, BSc PhD

  The Ritchie Centre, Monash Institute of Medical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 7, 2012
• First Posted: September 27, 2012
• Study Start: September 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 18, 2014

Record last verified: 2014-11

Locations

AU (1)