Melatonin in Pregnancy (MEL-P2)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03609086|
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : August 1, 2018
|Condition or disease||Intervention/treatment|
|Pregnancy||Other: Melatonin analysis|
Background Melatonin, a substance produced by the pineal gland, is well known for its role in the sleep-wake cycle but it is less well known as an effective antioxidant. It is able to access all parts of the cell, and can cross the blood-brain and placental barrier.
Melatonin has been reported to be synthesised in the placenta and may have both receptor mediated and non-receptor mediated protective functions during pregnancy. Severe pre-eclampsia has been reported to be associated with low levels of melatonin in the placenta although it is not known if the placental melatonin contributes to circulating levels.1,2 Despite this, melatonin levels have been proposed as a biomarker of pre-eclampsia. More information on the role of melatonin and metabolism of melatonin in pregnancy would inform planning of larger research studies to investigate the potential role for melatonin as a bio-marker for obstetric disease and potentially as a therapeutic agent in future.
Melatonin is synthesized endogenously from serotonin via two steps; the first, rate limiting step is arylalkylamine N-acetyltransferase mediated acetylation of serotonin to N-acetyl serotonin. The second step is methylation of N-acetyl serotonin via the enzyme hydroxyindole O-methyltransferase (also called N-acetylserotonin O-methyl-transferase).3,4 Interrogation of our database of next generation sequencing analysis of 80 human foetal livers revealed that the genes encoding these enzymes were not present although those encoding related acetyltransferases were. We can conclude that the human foetal liver is not a site of melatonin synthesis.
Our previous work found melatonin levels do however increase markedly during pregnancy and are up to 50-100 times higher than non-pregnant women in the third trimester (Figure). The physiological role of these elevated melatonin levels remains a supposition and the relationship of melatonin levels in the placenta with the maternal and foetal circulations at different stages of pregnancy are unclear. Melatonin synthesizing enzymes have been found in human placental tissue, however it is not clear whether placental production of melatonin is directly related to the elevated circulating maternal melatonin levels.
The production of melatonin is catalysed by specific enzymes and although these enzymes have been found in placental tissue, it is not known if the high melatonin levels in pregnancy come from the placenta and what the role of this melatonin is. It is proposed to measure melatonin in placentas and maternal/cord blood from women undergoing planned Caesarean section. The results should enable defining as to whether the placenta is a major source of melatonin and how the pattern of production changes in pregnancy. The blood samples taken from women having a Caesarean section and the umbilical cord will provide information about the role of melatonin at delivery.
If melatonin levels in the maternal circulation falls after delivery and placental tissue melatonin levels are well above limits of detection, then a firm conclusion that the placenta is the source of elevated maternal melatonin would be justified. This observational pilot study aims to measure 6-hydroxymelatonin sulphate levels in blood from women undergoing Caesarean section and umbilical cords, and from placental tissue.
This is an observational pilot study to investigate 6-hydroxymelatonin sulphate levels in blood from pregnant women immediately before and after delivery, from umbilical cord blood at the time of delivery and in samples of placental tissue.
Healthy pregnant women will be recruited at the pre-Caesarean section pre-assessment clinic.
|Study Type :||Observational|
|Estimated Enrollment :||15 participants|
|Official Title:||Investigation of Melatonin Production in Pregnancy: a Pilot Study to Define the Contribution of the Placenta|
|Actual Study Start Date :||June 6, 2018|
|Estimated Primary Completion Date :||August 31, 2018|
|Estimated Study Completion Date :||March 30, 2019|
- Other: Melatonin analysis
Measurement of 6-hydroxymelatonin
- 6-hydroxymelatonin sulphate in serum [ Time Frame: 24 hours after delivery ]Change in serum 6-hydroxymelatonin sulphate levels after delivery
- 6-hydroxymelatonin sulphate in serum [ Time Frame: Immediately after delivery ]Serum 6-hydroxymelatonin sulphate levels in umbilical cord blood after delivery
- 6-hydroxymelatonin sulphate in placental tissue [ Time Frame: Immediately after delivery ]Serum 6-hydroxymelatonin sulphate levels in placental tissue after delivery
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03609086
|Contact: Helen F Galley, phDfirstname.lastname@example.org|
|Contact: Andrea Woolner, MBChBemail@example.com|
|University of Aberdeen/NHS Grampian||Recruiting|
|Aberdeen, If Already Stated Select NOT Listed, United Kingdom, AB25 2ZD|
|Contact: Helen o Galley, PhD 01224437363 firstname.lastname@example.org|
|Contact: Helen F Galley 07900603649 email@example.com|
|Principal Investigator: Helen Galley, PhD|
|Aberdeen Maternity Hospital||Recruiting|
|Ellon, Lowland Scotland, United Kingdom, AB25 2ZB|
|Contact: Andrea MF Woolner, PhD FRCA 07900603649 firstname.lastname@example.org|
|Principal Investigator: Helen Galley, PhD FRCA|