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Trial registered on ANZCTR


Registration number
ACTRN12612000858897
Ethics application status
Approved
Date submitted
13/08/2012
Date registered
14/08/2012
Date last updated
10/09/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Melatonin to prevent brain injury in unborn growth restricted babies
Scientific title
A pilot study of maternally administered melatonin to decrease the level of oxidative stress in human pregnancies affected by intrauterine growth restriction.
Secondary ID [1] 280972 0
nil
Universal Trial Number (UTN)
U1111-1133-4541
Trial acronym
MEL trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intrauterine fetal growth restriction 287084 0
Condition category
Condition code
Reproductive Health and Childbirth 287411 287411 0 0
Fetal medicine and complications of pregnancy
Neurological 287412 287412 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 285418 0
Treatment: Drugs
Comparator / control treatment
No treatment. An historical control group will be used as a comparator. These women/pregnancies have been studied in 2011 and 2012. The historical group are women with healthy pregnancies and women with pregnancies affected by intrauterine growth restriction who have not received melatonin treatment, both groups of women have been treated at Monash Medical Centre. Data collected from these patients are derived from medical histories (clinical data regarding pregnancy and outcome) and from Monash Medical Centre maternal and umbilical cord blood, amniotic fluid and placental samples assessed for levels of oxidative stress (malondialdehyde and 8-isoprostane).
Control group
Historical

Outcomes
Primary outcome [1] 287674 0
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).
Timepoint [1] 287674 0
Birth
Secondary outcome [1] 298618 0
Maternal serum 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).
Timepoint [1] 298618 0
Before and during treatment. One bloodsample will be taken before treatment and weekly blood samples will be taken from the initiation of treatment until birth.
Secondary outcome [2] 298755 0
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.
Timepoint [2] 298755 0
Before and during treatment. Fetoplacental Doppler studies will be performed at least once before the start of melatonin treatment. During the period of melatonin treatment fetoplacental Doppler studies will be performed at least bi-weekly .
Secondary outcome [3] 298756 0
Placental 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).
Timepoint [3] 298756 0
Birth
Secondary outcome [4] 298757 0
Gestation at birth. This is calculated based using the last menstrual period in combination with data derived from ultrasound studies.
Timepoint [4] 298757 0
Birth
Secondary outcome [5] 298758 0
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.
Timepoint [5] 298758 0
Birth to discharge from hospital

Eligibility
Key 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
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Fetal demise
Multiple pregnancy
Known abnormal karyotype
Presence of any congenital abnormality
Unknown duration of pregnancy
IUGR attributable to non-placental factors

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment procedures are not applicable to this study as it is a small non-randomized pilot study.

The study population will consist of pregnant women undergoing prenatal care at Southern Health: Monash Medical Centre or Jessie McPherson Private Hospital, who meet the study's inclusion criteria. Potential participants will be identified through the antenatal clinic and the maternal fetal medicine unit at Monash Medical Centre. If considered eligible, the woman will be approached by the researcher, introduced to the trial, given the patient information sheet, counselled and invited to participate. Potential participants will be informed of the aims, methods and any reasonably anticipated benefits or potential hazards of the study. Subjects will be informed that their participation is voluntary and that they may withdraw consent to participate at any time during the study and that choosing not to participate will, in no way affect their care. Encouragement will be given to take as much time as necessary to consider participation and discuss their involvement with their partner and family. The women are informed that the researchers and other medical personnel are available to answer all their questions. Women are recruited to the study once written informed consent is obtained.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
7/09/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 285760 0
Charities/Societies/Foundations
Name [1] 285760 0
5-point foundation
Country [1] 285760 0
Australia
Funding source category [2] 285761 0
Other Collaborative groups
Name [2] 285761 0
The Ritchie Centre
Country [2] 285761 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Monash Institute of Medical Research
27-31 Wright Street,
Clayton, 3168
Victoria
Australia
Country
Australia
Secondary sponsor category [1] 284639 0
None
Name [1] 284639 0
Address [1] 284639 0
Country [1] 284639 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287771 0
Southern Health Human Research Ethics Committee B (EC00383)
Ethics committee address [1] 287771 0
Research Directorate
Level 4, Main Block,
Monash Medical Centre
246 Clayton Road
CLAYTON VIC 3168
Ethics committee country [1] 287771 0
Australia
Date submitted for ethics approval [1] 287771 0
Approval date [1] 287771 0
24/05/2012
Ethics approval number [1] 287771 0
12133B

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34532 0
Address 34532 0
Country 34532 0
Phone 34532 0
Fax 34532 0
Email 34532 0
Contact person for public queries
Name 17779 0
Nicole Alers
Address 17779 0
The Ritchie Centre
Monash Institute of Medical Research
P.O. Box 5418
Clayton, 3168
Victoria
Australia
Country 17779 0
Australia
Phone 17779 0
+61416000539
Fax 17779 0
Email 17779 0
[email protected]
Contact person for scientific queries
Name 8707 0
Nicole Alers
Address 8707 0
The Ritchie Centre
Monash Institute of Medical Research
P.O. Box 5418
Clayton, 3168
Victoria
Australia
Country 8707 0
Australia
Phone 8707 0
+61416000539
Fax 8707 0
Email 8707 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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