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

• ClinicalTrials.gov Identifier: NCT03952533
• Recruitment Status: Completed
• First Posted: May 16, 2019
• Last Update Posted: May 18, 2022
• Sponsor: University of Modena and Reggio Emilia
• Information provided by (Responsible Party): Prof. Fabio Facchinetti, University of Modena and Reggio Emilia

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cervical Shortening; Preterm Birth	Dietary Supplement: Dav	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Monocentric open label randomized controlled study
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Effects of the Supplementation of α-lipoic Acid (ALA), Magnesium, Vitamin B6 and Vitamin D to Women Presenting Risk Factor for Pre-term Birth
• Actual Study Start Date: May 5, 2019
• Actual Primary Completion Date: September 25, 2020
• Actual Study Completion Date: June 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: ALA; 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; 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)
No Intervention: Control; Control Group will be composed by women allocated in the "Control Group" and will not receive any supplementation but the standard care.

Outcome Measures

Primary Outcome Measures :

1. Cervical shortening [ Time Frame: from 11-14 weeks to 19-21 weeks of Gestational age ]
   Cervical shortening detected by the transvaginal ultrasound (TVS)
2. Rate of Short Cervix [ Time Frame: at 19-21 weeks of Gestational age ]
   Rate of cervical length < 25mm at the TVS exam
3. Rate of Preterm birth [ Time Frame: from 11-14 weeks to 37 weeks of Gestational age ]
   Number of preterm birth occurred

Secondary Outcome Measures :

1. Accesses to the ET for Threatened PTB [ Time Frame: from 11-14 weeks to 37 weeks of Gestational age ]
   Number of accesses to the ER for threatened PTB due to episodes of preterm uterine contractions and/or cervical shortening
2. Maternal hospitalization for threatened preterm labor [ Time Frame: from 11-14 weeks to 37 weeks of Gestational age ]
   Maternal need for hospital admission for threatened preterm labor

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 41 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Pregnant Women
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Nulliparous,
2. Previous History of preterm birth,
3. Age between 18 - 41 years,
4. 11-14 weeks of gestation,
5. BMI < 18 kg/m2 or ≥ 30 kg/m2,
6. Uterine myoma,
7. Hypertensive disorders either chronic or induced by the pregnancy

Exclusion Criteria:

1. PPROM,
2. Cervical dilation ≥ 1 cm

Contacts and Locations

Locations

Italy

University of Modena and Reggio Emilia

Modena, Mo, Italy, 41100

Sponsors and Collaborators

University of Modena and Reggio Emilia

More Information

Publications of Results:

Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009 Oct;1790(10):1149-60. doi: 10.1016/j.bbagen.2009.07.026. Epub 2009 Aug 4.

Grandi G, Mueller M, Bersinger N, Papadia A, Nirgianakis K, Cagnacci A, McKinnon B. Progestin suppressed inflammation and cell viability of tumor necrosis factor-alpha-stimulated endometriotic stromal cells. Am J Reprod Immunol. 2016 Oct;76(4):292-8. doi: 10.1111/aji.12552. Epub 2016 Aug 12.

Kim HS, Kim HJ, Park KG, Kim YN, Kwon TK, Park JY, Lee KU, Kim JG, Lee IK. Alpha-lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity. Exp Mol Med. 2007 Feb 28;39(1):106-13. doi: 10.1038/emm.2007.12.

De-Regil LM, Palacios C, Lombardo LK, Pena-Rosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2016 Jan 14;(1):CD008873. doi: 10.1002/14651858.CD008873.pub3.

Okitsu O, Mimura T, Nakayama T, Aono T. Early prediction of preterm delivery by transvaginal ultrasonography. Ultrasound Obstet Gynecol. 1992 Nov 1;2(6):402-9. doi: 10.1046/j.1469-0705.1992.02060402.x.

Berghella V, Roman A, Daskalakis C, Ness A, Baxter JK. Gestational age at cervical length measurement and incidence of preterm birth. Obstet Gynecol. 2007 Aug;110(2 Pt 1):311-7. doi: 10.1097/01.AOG.0000270112.05025.1d.

• Responsible Party: Prof. Fabio Facchinetti, Full Professor, University of Modena and Reggio Emilia
• ClinicalTrials.gov Identifier: NCT03952533
• Other Study ID Numbers: 0013213/19
• First Posted: May 16, 2019
• Last Update Posted: May 18, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Plan Description

All information required for this study in a manner strictly reserved to the norms of Good Clinical Practice (Legislative Decree 211/2003), as well as those relating to personal and sensitive data, c.d. Privacy Code (Legislative Decree 196/2003).

Personal data, including sensitive data, will be associated with a code, from which it will be impossible to trace back to its identity: only the investigating doctor will be able to link the code to his name.

The Specialist Doctor who follows the profession in the study, the people in charge of monitoring the study and the Regulatory Authorities have access to personal data, in compliance with and with the Guidelines of the Guarantor for the protection of personal data (Resolution No. 52 of 24 / 07/2008 and subsequent amendments and additions). The staff in charge of the study is in any case obliged to maintain the confidentiality of such information.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Prof. Fabio Facchinetti, University of Modena and Reggio Emilia:

alpha-lipoic Acid; vitamin D; cervical shortening; pretermbirth; food supplement

Additional relevant MeSH terms:

Premature Birth; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications