α-lipoic Acid (ALA), Magnesium, Vitamin B6 and Vitamin D and Risk Factor for Pre-term Birth

Study Overview
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Brief Summary
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Effects of oral administration of a food supplement constituted by α-lipoic acid, magnesium, vitamin B6 and vitamin D in tablets of 1,2 g administered daily to women presenting risk factors for preterm birth (PTB). The aim is to reduce the rate of short cervix at 19-21 weeks of gestational age and consequently reduce the occurrence of PTB.

Detailed Description
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The physiological course of pregnancy can be threatened by the onset of rhythmic and progressive uterine contractions, associated with a shortening and dilation of the cervix. These modifications occur as a consequence of inflammatory processes that involve important changes in the extracellular matrix of connective tissues. For this reason, in the event of a threat of preterm birth, the appropriate tocolytic therapies should be associated with interventions able to counteract morphological changes in the uterine cervix. Women presenting high or low BMI, presence of uterine myomas, metrorrhagia during the first trimester and hypertensive disorders are at risk for PTB. Current management practices remain profoundly various, without a therapeutic tocolytic strategy, especially because most of the first-line tocolytic drugs used present important side effects [8]. It is to be assessed whether a supplementation during pregnancy with minerals, vitamins, anti-inflammatory and anti-oxidant agents can avoid PTB in women with risk factors. ALA may interact synergistically with magnesium, vitamin B6 and vitamin D, limiting some of the main factors related to the risk of preterm delivery - probably via the inhibition of nuclear factor k beta (NF-kB)-signaling pathway - and reducing therefore the rate of uterine contractions. Moreover, the administration of ALA, magnesium, vitamin B6 and vitamin D have been demonstrated to be safe in pregnancy. The aim of the present study is to evaluate whether pregnant women presenting risk factors for PTB, treated with a combination of ALA, magnesium, vitamin 6 and vitamin D from 11-14 weeks of gestational age, until delivery, could present a reduced rate of cervical shortening measured by transvaginal ultrasound (TVS) at 11-14 weeks and 19-21 weeks of gestational age.

Official Title
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Effects of the Supplementation of α-lipoic Acid (ALA), Magnesium, Vitamin B6 and Vitamin D to Women Presenting Risk Factor for Pre-term Birth

Conditions
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Cervical Shortening, Preterm Birth

Intervention / Treatment
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* Dietary Supplement: Dav


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nulliparous, Previous History of preterm birth, Age between 18 - 41 years, 11-14 weeks of gestation, BMI < 18 kg/m2 or ≥ 30 kg/m2, Uterine myoma, Hypertensive disorders either chronic or induced by the pregnancy Exclusion Criteria: PPROM, Cervical dilation ≥ 1 cm

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 41 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Monocentric open label randomized controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALA<br>ALA Group will be composed of women allocated to the Treatment Group. These women will receive 2 tablets of Alpha lipoic Acid (ALA) as Dav® food supplement 1,2 g (Dav®, Lo.Li. Pharma, Rome, Italy) daily until delivery. | Dietary Supplement: Dav<br>* Daily oral administration of a food supplement constituted by α-lipoic acid, magnesium, vitamin B6 and vitamin D in tablets of 1,2 g (Dav®, Lo.Li. Pharma, Rome, Italy)<br>|
| No Intervention: Control<br>Control Group will be composed by women allocated in the Control Group and will not receive any supplementation but the standard care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cervical shortening | Cervical shortening detected by the transvaginal ultrasound (TVS) | from 11-14 weeks to 19-21 weeks of Gestational age | 
| Rate of Short Cervix | Rate of cervical length < 25mm at the TVS exam | at 19-21 weeks of Gestational age | 
| Rate of Preterm birth | Number of preterm birth occurred | from 11-14 weeks to 37 weeks of Gestational age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accesses to the ET for Threatened PTB | Number of accesses to the ER for threatened PTB due to episodes of preterm uterine contractions and/or cervical shortening | from 11-14 weeks to 37 weeks of Gestational age | 
| Maternal hospitalization for threatened preterm labor | Maternal need for hospital admission for threatened preterm labor | from 11-14 weeks to 37 weeks of Gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alpha-lipoic Acid, vitamin D, cervical shortening, pretermbirth, food supplement