Melatonin for Uterine Contractions in Pregnancy

(MelPreg Trial)

Overseen By Shadab A Rahman, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Must not be taking: Beta blockers, NSAIDs, CNS depressants, others

Disqualifiers: Color blind, Diabetes, Immunosuppressants, others

Compensation: Varies

Number of Visits: 2

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether melatonin affects uterine contractions in full-term pregnant women. Researchers administer melatonin at different times of the day and under various lighting conditions to observe its influence on contractions. The study compares results using both melatonin and a placebo (a harmless pill that resembles the real thing but has no effect). Women who are at least 38 weeks pregnant, have no previous births, and do not take certain medications might be suitable candidates. The goal is to understand how melatonin impacts labor, potentially improving care for pregnant women. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance labor care for future mothers.

Will I have to stop taking my current medications?

If you are taking prescription drugs that affect sleep, melatonin, or circadian rhythms, or medications that might interact with melatonin, you may need to stop them to participate in this trial. It's best to discuss your specific medications with the study team to determine eligibility.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that melatonin, a hormone often used to aid sleep, is generally safe for pregnant women. Studies have found that melatonin can reduce the risk of issues such as high blood pressure during pregnancy (pre-eclampsia), early birth, and growth problems in the baby.

In studies where pregnant women took melatonin, researchers found no major safety concerns. This suggests that melatonin is well-tolerated, with most people experiencing no serious side effects. Although melatonin has been studied in these contexts, individuals should consult their healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using melatonin for managing uterine contractions during pregnancy because it takes a different approach compared to traditional treatments like tocolytics, which often work by relaxing uterine muscles through hormonal pathways. Melatonin is a natural hormone known for regulating sleep, but it also has antioxidant and anti-inflammatory properties that might help calm uterine activity without the side effects associated with conventional medications. This treatment explores melatonin in both daytime and nighttime dosages, potentially offering a novel, more natural method to manage contractions and enhance maternal and fetal well-being.

What evidence suggests that this trial's treatments could be effective for uterine contractions in pregnancy?

Research has shown that melatonin might help manage uterine contractions during pregnancy. Studies have found a link between melatonin levels and these contractions, suggesting it could assist in labor. Melatonin appears to boost certain body processes that initiate labor. Some research also indicates that melatonin can improve pregnancy outcomes, such as increasing the chances of conception. This trial will evaluate different dosages of melatonin, including daytime and nighttime administration, to determine its effectiveness in controlling uterine contractions. These findings suggest that melatonin could be a useful treatment for managing uterine contractions. ^{1 3 4 6 7}

Who Is on the Research Team?

Elizabeth B Klerman, MD PhD

Principal Investigator

MGH

Are You a Good Fit for This Trial?

This trial is for first-time pregnant women aged 18-35, with a BMI under 36 before pregnancy, and at least 40 weeks into a single-fetus pregnancy. They must be receiving care from MassGeneralBrigham and planning to deliver at an MGB-affiliated institution. Women taking certain medications or with conditions affecting sleep, melatonin levels, or uterine contractions are excluded.

Inclusion Criteria

Planned admission for delivery at a MGB affiliated institution

BMI<36 pre-pregnancy

Pregnancy-associated obstetrical care by nurse midwife or physician associated with MassGeneralBrigham (MGB) (including hospital and community health centers)

Exclusion Criteria

Color blind

I am not taking any medications that could interact badly with melatonin.

I have a condition that could affect my melatonin levels or uterine contractions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Daytime Treatment

Participants receive exogenous melatonin during the day when endogenous levels are low

10 hours

1 visit (in-person)

Nighttime Treatment

Participants receive exogenous melatonin during the evening under lighting conditions expected to suppress endogenous melatonin

4 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Melatonin
• Placebo

Trial Overview The study tests if melatonin affects uterine contractions in full-term pregnant women. It involves giving exogenous melatonin during the day when natural levels are low and in the evening under light that suppresses natural melatonin production. Participants will either receive actual melatonin or a placebo.

How Is the Trial Designed?

Group I: Nighttime melatonin 0.5 mg Experimental Treatment 1 Intervention

Nighttime melatonin 0.5 mg

Group II: Daytime melatonin 3.0 mg Experimental Treatment 1 Intervention

Daytime melatonin 3.0 mg

Group III: Daytime melatonin 0.5 mg Experimental Treatment 1 Intervention

Daytime melatonin 0.5 mg

Group IV: Nighttime melatonin 0.0 mg Placebo Group 1 Intervention

Nighttime melatonin 0.0 mg

Group V: Daytime melatonin 0.0 mg Placebo Group 1 Intervention

Daytime melatonin 0.0 mg

Melatonin is already approved in European Union, United States for the following indications:

Approved in European Union as Circadin for:

• Insomnia in adults aged 55 and over
• Sleep disorders in children with autism spectrum disorder

Approved in European Union as Slenyto for:

• Insomnia in children and adolescents aged 2-18 with autism spectrum disorder

Approved in United States as Melatonin for:

• Sleep disorders in children with autism spectrum disorder
• Insomnia in adults

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Circadian rhythms, regulated by the suprachiasmatic nucleus and melatonin production, play a crucial role in pregnancy, influencing physiological processes and the timing of birth.

Melatonin may offer therapeutic benefits in improving pregnancy outcomes, potentially reducing risks of complications like preeclampsia and preterm birth by helping to align maternal and fetal circadian systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riding the Rhythm of Melatonin Through Pregnancy to Deliver on Time. McCarthy, R., Jungheim, ES., Fay, JC., et al.[2020]

A systematic review of 50 studies on oral melatonin supplementation found that 26 studies reported no significant adverse events, indicating a generally favorable safety profile for melatonin, especially when used according to natural circadian rhythms.

While most adverse events were minor and manageable, some studies noted potential impacts on endocrine and cardiovascular functions, suggesting that dosage and timing are important factors to consider in melatonin use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with oral administration of melatonin: A critical systematic review of clinical evidence. Foley, HM., Steel, AE.[2019]

Melatonin is a crucial hormone during pregnancy, as it crosses the placenta easily and helps regulate biological rhythms, which may be essential for a successful pregnancy.

The hormone has multiple roles, including acting as an endocrine modulator and antioxidant, and it may help address complications such as abortion, pre-eclampsia, and fetal brain damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin and pregnancy in the human. Tamura, H., Nakamura, Y., Terron, MP., et al.[2018]

Melatonin does not directly affect uterine contractility on its own, but it enhances contractions when combined with noradrenaline, suggesting a potential role in modulating uterine activity.

The study, which involved uterine tissue samples from women at full term during caesarean sections, indicates that melatonin may influence the timing of labor, particularly since labor often starts in the evening when melatonin levels are higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin together with noradrenaline augments contractions of human myometrium. Mårtensson, LG., Andersson, RG., Berg, G.[2019]

Melatonin has demonstrated a tocolytic effect, meaning it can help inhibit uterine contractions, based on experiments conducted on isolated uterine horns in various animal models.

The research suggests that melatonin works by antagonizing the effects of oxytocin, which is known to induce uterine contractions, indicating a potential mechanism of action for its tocolytic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The tocolytic activity of melatonin]. Drogovoz, SM., Ryzhenko, IM.[2014]

Melatonin receptors (MT1 and MT2) are expressed in the myometrial tissues of both pregnant and nonpregnant women, suggesting that melatonin may play a role in regulating uterine contractions during childbirth.

The study found that melatonin can differentially affect cAMP signaling in myocytes based on the reproductive state, indicating its potential to modulate myometrial function and possibly lead to new treatments for childbirth-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The human myometrium as a target for melatonin. Schlabritz-Loutsevitch, N., Hellner, N., Middendorf, R., et al.[2015]

Melatonin receptors, specifically MTNR1B, are present in the human myometrium during late-term pregnancy and play a crucial role in enhancing uterine contractions by working together with oxytocin signaling.

Exposure to white light can inhibit melatonin levels, which in turn reversibly suppresses uterine contractions, highlighting the importance of melatonin in regulating labor timing and intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical significance of melatonin receptors in the human myometrium. Olcese, J., Beesley, S.[2014]

A study involving women in the late third trimester of pregnancy found a significant positive relationship between circulating melatonin levels and the frequency of uterine contractions, suggesting that melatonin may play a role in initiating labor.

For every 10 pg/mL*h increase in melatonin concentration, there was an increase of 1.4 to 2.1 contractions per 30 minutes, indicating that melatonin levels can be influenced by light exposure and may have clinical implications for managing labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between endogenous melatonin concentrations and uterine contractions in late third trimester of human pregnancy. Rahman, SA., Bibbo, C., Olcese, J., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9775355/

The Role of Melatonin in Pregnancy and the Health Benefits ... The result of this study confirmed that there is a positive relationship between melatonin concentrations and uterine contractions in women ...

2. frontiersin.org frontiersin.org/journals/reproductive-health/articles/10.3389/frph.2025.1680984/pdf

Melatonin improved the outcomes of women with ART Data sources: PubMed/MEDLINE, Embase, and Cochrane Library. Results: Melatonin supplementation significantly improved clinical pregnancy rate.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6753220/

Riding the Rhythm of Melatonin Through Pregnancy to ... Together, these data suggest that melatonin enhances noradrenaline-dependent contractions to help initiate labor. Second, melatonin acts in cooperation with ...

4. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.14951

A double‐blind, randomized, placebo‐controlled trial of ... The melatonin group had significantly lower rates of spontaneous vaginal birth within 24 h (35.0% vs. 50.0%; RR 0.70 95% CI 0.50–0.98). The ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0890623824000017

Melatonin-mediated actions and circadian functions that ... The data summarized in this report indicate that melatonin use may enhance the functional efficiency of the placenta-uterine unit. A deficiency in this ...

6. womensmentalhealth.org womensmentalhealth.org/posts/you-asked-is-it-safe-to-take-melatonin-during-pregnancy/

You Asked: Is It Safe to Take Melatonin During Pregnancy? It has been shown that supplementation with melatonin decreases the risk of pre-eclampsia, preterm birth and intrauterine growth retardation (IUGR).

7. womensmentalhealth.org womensmentalhealth.org/posts/update-2020-melatonin-pregnancy/

Clinical Update 2020: Melatonin and Pregnancy It has been shown that supplementation with melatonin decreases the risk of pre-eclampsia, preterm birth and intrauterine growth retardation (IUGR).