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

Preterm Birth Clinical Trial

— ALA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03952533
• Other study ID #: 0013213/19
• Status: Completed
• Phase: N/A
• Start date: May 5, 2019
• Est. completion date: June 1, 2021

Study information

• Verified date: May 2022
• Source: University of Modena and Reggio Emilia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: June 1, 2021
• Est. primary completion date: September 25, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 41 Years

Eligibility

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

Related Conditions & MeSH terms

• Cervical Shortening
• Premature Birth
• Preterm Birth

Intervention

Dietary Supplement:
• Dav
Daily oral administration of a food supplement constituted by a-lipoic acid, magnesium, vitamin B6 and vitamin D in tablets of 1,2 g (Dav®, Lo.Li. Pharma, Rome, Italy)

Locations

Country	Name	City	State
Italy	University of Modena and Reggio Emilia	Modena	Mo

Sponsors (1)

Lead Sponsor	Collaborator
University of Modena and Reggio Emilia

Country where clinical trial is conducted

Italy, 

References & Publications (6)

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. — View Citation

De-Regil LM, Palacios C, Lombardo LK, Peña-Rosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2016 Jan 14;(1):CD008873. doi: 10.1002/14651858.CD008873.pub3. Review. Update in: Cochrane Database Syst Rev. 2019 Jul 2 — View Citation

Grandi G, Mueller M, Bersinger N, Papadia A, Nirgianakis K, Cagnacci A, McKinnon B. Progestin suppressed inflammation and cell viability of tumor necrosis factor-a-stimulated endometriotic stromal cells. Am J Reprod Immunol. 2016 Oct;76(4):292-8. doi: 10. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

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