Preterm LaborNCT07305519
The Combined Effect of Magnesium, Palmitoylethanolamide, High-Molecular-weight Hyaluronic Acid, Vitamin B6, and Vitamin D in Preventing Preterm Birth:
A study testing Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal Progesterone and Standard Treatment (Guideline-Based) in people with Preterm Labor, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
The aim of the study is to assess the effect of a combination of Magnesium, Palmitoylethanolamide, high-molecular-weight Hyaluronic Acid, Vitamin B6, and Vitamin D in women at risk of preterm birth (PTB). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Preterm Labor
- What is being tested?
- Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal Progesterone and Standard Treatment (Guideline-Based)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteItaly
- Study dates
- 1 Apr 2026to 1 Jan 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent
- Singleton pregnancy
- Maternal age ≥ 18 years
- Gestational age between 20+0 and 34+0 weeks at enrollment
- Cervical length between 15 mm and 30 mm measured by transvaginal ultrasound
Who cannot join
- Fetal structural anomalies
- Maternal chronic diseases or pregnancy-related conditions, including diabetes, hypertension, preeclampsia, cardiovascular disease, infections, or autoimmune disorders
- Multiple gestation
- Fetal growth abnormalities (estimated fetal weight <10th or >90th percentile)
- Prelabor rupture of membranes (PROM)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: The Combined Effect of Magnesium, Palmitoylethanolamide, High-Molecular-weight Hyaluronic Acid, Vitamin B6, and Vitamin D in Preventing Preterm Birth: A Randomized Controlled Trial
The aim of the study is to assess the effect of a combination of Magnesium, Palmitoylethanolamide, high-molecular-weight Hyaluronic Acid, Vitamin B6, and Vitamin D in women at risk of preterm birth (PTB).
Read the detailed description
Preterm birth (PTB) remains one of the leading causes of neonatal morbidity and mortality worldwide. The transition of the myometrium from a quiescent state to active contractility is driven by a complex interplay of genetic predisposition, inflammatory mediators, endocrine factors, and uterine environmental conditions. Increased expression of pro-inflammatory cytokines (including IL-6, IL-1β, TNF-α), activation of NF-κB pathways, prostaglandin synthesis, cervical remodeling, and alterations in progesterone signaling contribute to the premature onset of labor.
Several natural molecules have demonstrated potential roles in modulating uterine quiescence, inflammatory pathways, and cervical integrity. Magnesium participates in more than 600 enzymatic reactions and reduces inflammatory cytokine production, while low serum magnesium levels have been associated with a higher risk of PTB. Vitamin B6 contributes to fetal neurodevelopment and has been linked to reduced rates of preeclampsia and preterm birth. High-molecular-weight hyaluronic acid (HMWHA) plays a crucial role in immune tolerance at the maternal-fetal interface, promotes anti-inflammatory cytokine secretion, and supports progesterone-mediated uterine quiescence through upregulation of the progesterone receptor membrane component-1 (PGRMC1). Palmitoylethanolamide (PEA), an endogenous bioactive lipid, exerts anti-inflammatory and mast-cell-stabilizing properties and has been found at significantly higher levels in women with PTB as part of a compensatory physiological response. Vitamin D, a steroid-like hormone, modulates immune pathways and downregulates CRH, prostaglandin production, and oxytocin signaling, all of which are implicated in the initiation of labor.
This randomized, prospective, open-label pilot study aims to evaluate whether the combination of Magnesium, Palmitoylethanolamide, high-molecular-weight Hyaluronic Acid, Vitamin B6, and Vitamin D, administered in addition to standard vaginal progesterone, can reduce the incidence of preterm birth in women at increased risk due to a sonographic cervical length of 15-30 mm between 20 and 34 weeks' gestation.
A total of 150 women with singleton pregnancies will be randomized 1:1 to receive either standard care with vaginal progesterone alone (control group) or vaginal progesterone plus the oral combination supplement (treatment group). Cervical length will be assessed at baseline, 1 week, and 2 weeks after enrollment. Participants will be followed until 37 weeks of gestation or delivery.
The primary outcome is the proportion of women delivering at or beyond 36 weeks of gestation. Secondary outcomes include the incidence of preterm uterine contractions, emergency department visits for uterine contractions, time interval from treatment initiation to delivery, and longitudinal changes in cervical length.
As the first study to investigate this specific molecular association for PTB prevention, it is designed as a pilot trial to generate preliminary efficacy data and inform future larger randomized controlled studies.
- Conditions
- Preterm Labor
- Being tested
- Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal Progesterone, Standard Treatment (Guideline-Based)
- Keywords
- preterm labor, preterm birth, prematurity, magnesium, hyaluronic acid, vitamin B6, Vitamin D
- Medical subject headings
- Obstetric Labor, Premature, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal ProgesteroneDrug
Participants randomized to the treatment arm will receive a combination oral supplement containing Magnesium (450 mg), Palmitoylethanolamide (200 mg), high-molecular-weight Hyaluronic Acid (200 mg), Vitamin B6 (2.6 mg), and Vitamin D (50 µg / 2000 IU), administered as two tablets per day. The supplement will be given in addition to standard vaginal progesterone (200 mg once daily). Treatment begins at enrollment (20-34 weeks' gestation) and continues until 37 weeks of gestati
Standard Treatment (Guideline-Based)Other
Participants randomized to the control arm will receive standard therapy consisting of vaginal progesterone (200 mg once daily) from enrollment (20-34 weeks' gestation) until 37 weeks of gestation. No additional supplements or investigational products will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Treatment: Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal Progesterone | Experimental | Not described Receives: Drug: Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal Progesterone |
| Control: Vaginal Progesterone Only | Active comparator | Not described Receives: Other: Standard Treatment (Guideline-Based) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preterm Birth before 37 weeks
Proportion of participants who deliver before 37+0 weeks of gestation in each study arm.
Measured: Up to 37 weeks of gestation or delivery, whichever occurs first.
Secondary outcomes (5)
Incidence of Preterm Uterine Contractions
Number of episodes of uterine contractions requiring clinical evaluation, as reported by participants or documented during hospital visits.
Measured: From enrollment until 37 weeks of gestation or delivery.
Emergency Department Visits for Preterm Contraction
Number of emergency department or obstetric triage visits due to symptoms of preterm uterine activity.
Measured: From enrollment until 37 weeks of gestation or delivery.
Interval From Treatment Initiation to Delivery
Number of days between study enrollment (start of therapy) and delivery.
Measured: From baseline (T0) to delivery.
Change in Cervical Length at 1 Week
Difference in transvaginal cervical length (mm) between baseline and 1 week after randomization.
Measured: Baseline (T0) and 1 week (T1).
Change in Cervical Length at 2 Weeks
Difference in transvaginal cervical length (mm) between baseline and 2 weeks after randomization.
Measured: Baseline (T0) and 2 weeks (T2).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2025
- Study start1 Apr 2026
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Preterm LaborStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giuseppe Rizzo, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07305519
- Sponsor's protocol ID
- PEATB_2025
- Status last verified
- Apr 2026
- First submitted
- 12 Dec 2025
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Combined Effect of Magnesium, Palmitoylethanolamide, High-Molecular-weight Hyaluronic Acid, Vitamin B6, and Vitamin D in Preventing Preterm Birth: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07305519
- Acronym / sponsor ID
- PEATB_2025
- Conditions
- Preterm Labor
- Keywords
- preterm labor, preterm birth, prematurity, magnesium, hyaluronic acid, vitamin B6, Vitamin D
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- 1 Apr 2026 (actual)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 26 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to assess the effect of a combination of Magnesium, Palmitoylethanolamide, high-molecular-weight Hyaluronic Acid, Vitamin B6, and Vitamin D in women at risk of preterm birth (PTB).
Detailed description
Preterm birth (PTB) remains one of the leading causes of neonatal morbidity and mortality worldwide. The transition of the myometrium from a quiescent state to active contractility is driven by a complex interplay of genetic predisposition, inflammatory mediators, endocrine factors, and uterine environmental conditions. Increased expression of pro-inflammatory cytokines (including IL-6, IL-1β, TNF-α), activation of NF-κB pathways, prostaglandin synthesis, cervical remodeling, and alterations in progesterone signaling contribute to the premature onset of labor.
Several natural molecules have demonstrated potential roles in modulating uterine quiescence, inflammatory pathways, and cervical integrity. Magnesium participates in more than 600 enzymatic reactions and reduces inflammatory cytokine production, while low serum magnesium levels have been associated with a higher risk of PTB. Vitamin B6 contributes to fetal neurodevelopment and has been linked to reduced rates of preeclampsia and preterm birth. High-molecular-weight hyaluronic acid (HMWHA) plays a crucial role in immune tolerance at the maternal-fetal interface, promotes anti-inflammatory cytokine secretion, and supports progesterone-mediated uterine quiescence through upregulation of the progesterone receptor membrane component-1 (PGRMC1). Palmitoylethanolamide (PEA), an endogenous bioactive lipid, exerts anti-inflammatory and mast-cell-stabilizing properties and has been found at significantly higher levels in women with PTB as part of a compensatory physiological response. Vitamin D, a steroid-like hormone, modulates immune pathways and downregulates CRH, prostaglandin production, and oxytocin signaling, all of which are implicated in the initiation of labor.
This randomized, prospective, open-label pilot study aims to evaluate whether the combination of Magnesium, Palmitoylethanolamide, high-molecular-weight Hyaluronic Acid, Vitamin B6, and Vitamin D, administered in addition to standard vaginal progesterone, can reduce the incidence of preterm birth in women at increased risk due to a sonographic cervical length of 15-30 mm between 20 and 34 weeks' gestation.
A total of 150 women with singleton pregnancies will be randomized 1:1 to receive either standard care with vaginal progesterone alone (control group) or vaginal progesterone plus the oral combination supplement (treatment group). Cervical length will be assessed at baseline, 1 week, and 2 weeks after enrollment. Participants will be followed until 37 weeks of gestation or delivery.
The primary outcome is the proportion of women delivering at or beyond 36 weeks of gestation. Secondary outcomes include the incidence of preterm uterine contractions, emergency department visits for uterine contractions, time interval from treatment initiation to delivery, and longitudinal changes in cervical length.
As the first study to investigate this specific molecular association for PTB prevention, it is designed as a pilot trial to generate preliminary efficacy data and inform future larger randomized controlled studies.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment: Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal Progesterone | Experimental | Drug: Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal Progesterone |
| Control: Vaginal Progesterone Only | Active comparator | Other: Standard Treatment (Guideline-Based) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Signed informed consent
- Singleton pregnancy
- Maternal age ≥ 18 years
- Gestational age between 20+0 and 34+0 weeks at enrollment
- Cervical length between 15 mm and 30 mm measured by transvaginal ultrasound
Key exclusion criteria (5 listed)
- Fetal structural anomalies
- Maternal chronic diseases or pregnancy-related conditions, including diabetes, hypertension, preeclampsia, cardiovascular disease, infections, or autoimmune disorders
- Multiple gestation
- Fetal growth abnormalities (estimated fetal weight <10th or >90th percentile)
- Prelabor rupture of membranes (PROM)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal ProgesteroneParticipants randomized to the treatment arm will receive a combination oral supplement containing Magnesium (450 mg), Palmitoylethanolamide (200 mg), high-molecular-weight Hyaluronic Acid (200 mg), Vitamin B6 (2.6 mg), and Vitamin D (50 µg / 2000 IU), administered as two tablets per day. The supplement will be given in addition to standard vaginal progesterone (200 mg once daily). Treatment begins at enrollment (20-34 weeks' gestation) and continues until 37 weeks of gestati | Drug | Treatment: Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal Progesterone |
| Standard Treatment (Guideline-Based)Participants randomized to the control arm will receive standard therapy consisting of vaginal progesterone (200 mg once daily) from enrollment (20-34 weeks' gestation) until 37 weeks of gestation. No additional supplements or investigational products will be administered. | Other | Control: Vaginal Progesterone Only |
Primary outcome
Preterm Birth before 37 weeks
Time frame: Up to 37 weeks of gestation or delivery, whichever occurs first.
Proportion of participants who deliver before 37+0 weeks of gestation in each study arm.
5 secondary outcomes
Incidence of Preterm Uterine Contractions
Time frame: From enrollment until 37 weeks of gestation or delivery.
Emergency Department Visits for Preterm Contraction
Time frame: From enrollment until 37 weeks of gestation or delivery.
Interval From Treatment Initiation to Delivery
Time frame: From baseline (T0) to delivery.
Change in Cervical Length at 1 Week
Time frame: Baseline (T0) and 1 week (T1).
Change in Cervical Length at 2 Weeks
Time frame: Baseline (T0) and 2 weeks (T2).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Magnesium-PEA-HMW Hyaluronic Acid-Vitamin B6-Vitamin D + Vaginal Progesterone and Standard Treatment (Guideline-Based) in people with Preterm Labor, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giuseppe RIZZO, Professor (+393386973001, giuseppe.rizzo@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Preterm Birth before 37 weeks (time frame: Up to 37 weeks of gestation or delivery, whichever occurs first.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.