Melatonin to Prevent Brain Injury in Unborn Growth Restricted Babies

Study Overview
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Brief Summary
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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.

Official Title
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A Pilot Study of Maternally Administered Melatonin to Decrease the Level of Oxidative Stress in Human Pregnancies Affected by Intrauterine Growth Restriction.

Conditions
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Fetal Growth Retardation

Intervention / Treatment
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* Drug: Melatonin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin<br>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<br>* 4mg prolonged release melatonin oral tablets twice daily<br>* Other names: Circadin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative stress in maternal venous serum | 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). | 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 | 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. | 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 | 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) | Once, at birth. | 
| Gestational age at birth. | Gestational age at birth will be calculated using the last menstrual period and ultrasound characteristics. | Once, at birth. | 
| Composite neonatal outcome. | 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. | Participants will be followed for the duration of hospital stay, up to 12 months. |