Melatonin to Prevent Brain Injury in Unborn Growth Restricted Babies

• ClinicalTrials.gov Identifier: NCT01695070
• Recruitment Status: Completed
• First Posted: September 27, 2012
• Last Update Posted: November 18, 2014
• Sponsor: Monash University
• Information provided by (Responsible Party): Nicole Alers, Monash University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fetal Growth Retardation	Drug: Melatonin	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Maternally Administered Melatonin to Decrease the Level of Oxidative Stress in Human Pregnancies Affected by Intrauterine Growth Restriction.
• Study Start Date: September 2012
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: November 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Melatonin; 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; 4mg prolonged release melatonin oral tablets twice daily; Other Name: Circadin

Outcome Measures

Primary Outcome Measures :

1. Oxidative stress in the umbilical artery [ Time Frame: Once, at birth. ]
   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).

Secondary Outcome Measures :

1. Oxidative stress in maternal venous serum [ Time Frame: Once within one week before start treatment and once per week during the treatment period (estimated to be an average of 4 weeks). ]
   Maternal serum oxidative stress will be assessed 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).
2. Fetoplacental Doppler studies [ Time Frame: Once within one week before start treatment and twice per week during the treatment period (estimated to be an average of 4 weeks). ]
   Fetoplacental Doppler studies (umbilical artery, uterine artery, middle cerebral artery, ductus venosus). Fetoplacental Doppler studies are performed in the clinical assessment of women diagnosed with intrauterine growth restriction by sonography.
3. Placental oxidative stress [ Time Frame: Once, at birth. ]
   Placental oxidative stress is assessed 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)
4. Gestational age at birth. [ Time Frame: Once, at birth. ]
   Gestational age at birth will be calculated using the last menstrual period and ultrasound characteristics.
5. Composite neonatal outcome. [ Time Frame: Participants will be followed for the duration of hospital stay, up to 12 months. ]
   Composite neonatal outcome (admission to NICU, duration of admission, need and duration of respiratory support, intraventricular haemorrhage, necrotising enterocolitis, abnormal neurological assessment, mortality before discharge). This composite neonatal outcome will be measured by collecting medical record data after clinical assessments.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.
• 18 years or older.
• Consent obtained.

Exclusion Criteria:

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

Contacts and Locations

Locations

Australia, Victoria

Southern Health: Monash Medical Centre and Jessie McPherson Private Hospital

Clayton, Victoria, Australia, 3168

Sponsors and Collaborators

Monash University

Investigators

• Principal Investigator: 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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Nicole Alers, MD, Monash University
• ClinicalTrials.gov Identifier: NCT01695070
• Other Study ID Numbers: U1111-1133-4541; ACTRN12612000858897 ( Registry Identifier: Australian New Zealand Clinical Trial Registry )
• First Posted: September 27, 2012
• Last Update Posted: November 18, 2014
• Last Verified: November 2014

Additional relevant MeSH terms:

Fetal Growth Retardation; Fetal Diseases; Pregnancy Complications; Growth Disorders; Pathologic Processes; Melatonin; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Central Nervous System Depressants