Clinical trial NCT03952533: α-lipoic Acid (ALA), Magnesium, Vitamin B6 and Vitamin D and Risk Factor for Pre-term Birth
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cervical Shortening
Preterm Birth
Keywords: alpha-lipoic Acid
vitamin D
cervical shortening
pretermbirth
food supplement
Lead sponsor: University of Modena and Reggio Emilia
Sponsor class: OTHER
First posted: 2019-05-16
Enrollment: 122
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Monocentric open label randomized controlled study
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Cervical shortening
timeFrame: from 11-14 weeks to 19-21 weeks of Gestational age
measure: Rate of Short Cervix
timeFrame: at 19-21 weeks of Gestational age
measure: Rate of Preterm birth
timeFrame: from 11-14 weeks to 37 weeks of Gestational age
Secondary outcomes:
measure: Accesses to the ET for Threatened PTB
timeFrame: from 11-14 weeks to 37 weeks of Gestational age
measure: Maternal hospitalization for threatened preterm labor
timeFrame: from 11-14 weeks to 37 weeks of Gestational age
Other outcomes:
Locations:
city: Modena
country: Italy
facility: University of Modena and Reggio Emilia
state: Mo
Study officials:
References:
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.
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-alpha-stimulated endometriotic stromal cells. Am J Reprod Immunol. 2016 Oct;76(4):292-8. doi: 10.1111/aji.12552. Epub 2016 Aug 12.
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. doi: 10.1038/emm.2007.12.
citation: 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.
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. doi: 10.1046/j.1469-0705.1992.02060402.x.
citation: 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.