Melatonin and Perinatal Outcomes in MVM-Related Fetal Growth Restriction (MIMVMFGR) (MIMVMFGR)

A Randomized Controlled Clinical Trial to Explore the Effectiveness of Melatonin as a Perinatal Intervention in Maternal Vascular Malperfusion-Associated Fetal Growth Restriction

The goal of this clinical trial is to evaluate the efficacy and safety of melatonin in the treatment of early-onset severe maternal vascular malperfusion-related fetal growth restriction (MVM-FGR), and to determine its effects on fetal growth and perinatal outcomes. The study will enroll pregnant women with singleton pregnancies diagnosed with severe MVM-FGR between 24+0 and 31+6 weeks of gestation.

The main questions it aims to answer are:

• Whether melatonin treatment can reduce the incidence of a composite adverse neonatal outcome, including neonatal death and severe neonatal complications.
• Whether melatonin treatment can improve pregnancy and neonatal outcomes, including the interval from treatment initiation to delivery, gestational age at delivery, fetal growth trajectory throughout pregnancy (Z-score slope over time estimated using linear mixed models), neonatal birthweight, Apgar scores, neonatal complications (such as respiratory distress syndrome), maternal adverse events (such as hypertensive disorders of pregnancy), and placental pathological findings.

Researchers will compare participants receiving a placebo (one capsule taken at bedtime, identical in appearance and size to melatonin) with those receiving melatonin to determine whether melatonin improves these maternal and neonatal outcomes.

Participants will:

• Take melatonin 10 mg orally once nightly at bedtime.

Study Overview

• Status: Enrolling by invitation
• Conditions: Fetal Growth Restriction (FGR)
• Intervention / Treatment: Drug: Melatonin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200092
      • Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Singleton pregnancy
2. intact membranes
3. detectable fetal cardiac activity, and normal fetal movements.
4. Diagnosis of isolated maternal vascular malperfusion-related fetal growth restriction (MVM-FGR) between 24+0 and 31+6 weeks of gestation, defined as:

1) Estimated fetal weight (EFW) or abdominal circumference (AC) below the 10th percentile for gestational age, and uterine artery pulsatility index (UtA-PI) or umbilical artery pulsatility index (UA-PI) ≥95th percentile; or 2) Absent or reversed end-diastolic flow in the umbilical artery, regardless of estimated fetal weight.

(5) Willingness to participate in the study, ability to comply with the observation and treatment protocol, and provision of written informed consent.

Exclusion Criteria:

1. Presence of severe acute or chronic maternal diseases that make continuation of pregnancy unsafe.
2. Fetal structural anomalies, genetic abnormalities, or intrauterine infections.
3. Immediate need for pregnancy termination prior to enrollment, such as absent a-wave in the ductus venosus, preterminal cardiotocography (CTG), or a critically abnormal biophysical profile (BPP).
4. Treatment within 1 month prior to enrollment with medications such as low-molecular-weight heparin, aspirin, sildenafil, or traditional Chinese medicine aimed at preventing miscarriage or supporting pregnancy.
5. Individuals with legally defined disabilities (including visual impairment, hearing impairment, speech impairment, intellectual disability, mental disorders, or physical disability) and patients with psychiatric illness.
6. Participation in another clinical trial within the past 3 months.
7. A history of smoking more than 10 cigarettes per day within 3 months prior to screening.
8. Suspected or confirmed alcohol or substance abuse.
9. Known allergy to melatonin or any component of the investigational product.
10. Any other condition that, in the investigator's judgment, makes the participant unsuitable for this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: melatonin group; Take melatonin 10 mg orally once nightly at bedtime	Drug: Melatonin; Take melatonin 10 mg orally once nightly at bedtime
Placebo Comparator: placebo group; receiving a placebo (one capsule taken at bedtime, identical in appearance and size to melatonin)	Drug: Placebo; receiving a placebo (one capsule taken at bedtime, identical in appearance and size to melatonin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IUFD and neonatal death	intrauterine fetal death and neonatal death	during the whole pregnancy and born within 28 days
severe neonatal complications.	severe neonatal complications ( including neonatal necroticing enterocolitis, Respiratory Distress Syndrome, neonatal septicemnia, Periventricular-intraventricular hemorrhage).	born within 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
interval from treatment to delivery	the interval from treatment initiation to delivery (day);	during the whole pregnancy
delivery GA	gestational age at delivery (week)	the day at delivery
fetal growth trajectory throughout pregnancy	fetal growth trajectory throughout pregnancy (slope of Z-score over time estimated using a linear mixed model, LMM);	during the whole pregnancy
neonatal birth weight	neonatal birth weight(g)	the day at delivery
Apgar score	neonatal Apgar score	the day at delivery
maternal complications	including gestational hypertension, preeclampsia, and placental abruption	during pregnancy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term neurodevelopmental outcomes of the infant	Incidence of cerebral palsy, and neurodevelopmental assessment (the Bayley Scales of Infant and Toddler Development).	within 2 years after baby is born
effect of melatonin on placental oxidative stress levels	placental Malondialdehyde (MDA) levels, superoxide dismutase (SOD), and placental growth factor (PlGF) activity	the delivery day

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: melatonin; FGR
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Fetal Diseases; Growth Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Fetal Growth Retardation; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Tryptamines; Melatonin
• Other Study ID Numbers: XH-26-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be publicly posted in a repository. After publication of the main study results, de-identified IPD may be made available upon reasonable request to the study investigators by email, subject to review of the request, institutional approvals, applicable regulations, and data use agreements intended to protect participant privacy and confidentiality.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No