Clinical trial NCT03992534: The FLIP-1 Study: Vaginal Lactobacillus Supplementation in Women at High Risk of Preterm Birth
Official title: Feasibility, Safety, Tolerance and Assessment of LACTIN-V Use in a Cohort of Pregnant Women at Risk of Preterm Birth
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Preterm Labor
Preterm Birth
Preterm Premature Rupture of Membrane
Cervical Incompetence
Miscarriage in Second Trimester
Miscarriage in Third Trimester
Keywords: Pregnancy
Preterm labour
Preterm delivery
Vaginal microbiome
Infection
Next generation sequencing
Lactobacillus
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Imperial College Healthcare NHS Trust
First posted: 2019-06-20
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Preterm birth (PTB) is the primary cause of infant death worldwide. It has been shown that a vaginal microbiota deplete in Lactobacillus species is a risk factor for preterm labour. Conversely a vaginal microbiota dominated by Lactobacillus crispatus appears to be protective for these adverse outcomes. A wide range of 'over the counter' Lactobacillus spp. containing products targeted at 'vaginal health' and formulated for vaginal administration are available, but most of them do not contain vaginal species of Lactobacillus. The primary aim of this study is to determine whether vaginal supplementation with L. crispatus CTV-05 is associated with colonisation.

Detailed description: Pregnant women at Queen Charlotte's and Chelsea Hospital and St Mary's Hospital London who are defined as being at a higher than background risk for preterm labour will be recruited into this study. Women at risk of pre-term labour will include those with either previous LLETZ, previous preterm birth, previous second trimester pregnancy loss or a combination of these indications.

As part of this interventional study, subjects will be offered supplementation with L. crispatus CTV-05. The preparation of LACTIN-V is administered vaginally using a specially designed applicator.

The primary aim of this study is to determine whether vaginal supplementation with L. crispatus CTV-05 is associated with colonisation.

Eligibility criteria: Inclusion Criteria:

* Women at risk of preterm labour
* Women referred to the prematurity clinic
* Women with previous LLETZ (large loop excision of the transformation zone)
* Women with previous preterm birth
* Women with previous second trimester loss

Exclusion Criteria:

* HIV positive women
* Women who are unable to provide informed consent
* Women aged \<18
* Women receiving antibiotic treatment within 1 week of recruitment

Primary outcomes:
measure: The number of participants that demonstrate a change in vaginal colonisation during and following LACTIN-V use.
timeFrame: 2-4 years
Secondary outcomes:
measure: The number of participants with treatment related adverse events following LACTIN-V supplementation in pregnant women at high risk of preterm birth.
timeFrame: 2-4 years
measure: The number of patients using LACTIN-V that go on to experience preterm birth, PPROM or cervical shortening.
timeFrame: 2-4 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Institute of Reproductive Developmental Biology, Hammersmith Hospital
Study officials:
affiliation: Imperial College London
name: Phillip Bennett, BSc PhD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: MacIntyre DA, Chandiramani M, Lee YS, Kindinger L, Smith A, Angelopoulos N, Lehne B, Arulkumaran S, Brown R, Teoh TG, Holmes E, Nicoholson JK, Marchesi JR, Bennett PR. The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci Rep. 2015 Mar 11;5:8988. doi: 10.1038/srep08988.
citation: Brown RG, Marchesi JR, Lee YS, Smith A, Lehne B, Kindinger LM, Terzidou V, Holmes E, Nicholson JK, Bennett PR, MacIntyre DA. Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin. BMC Med. 2018 Jan 24;16(1):9. doi: 10.1186/s12916-017-0999-x.
citation: Kindinger LM, Bennett PR, Lee YS, Marchesi JR, Smith A, Cacciatore S, Holmes E, Nicholson JK, Teoh TG, MacIntyre DA. The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk. Microbiome. 2017 Jan 19;5(1):6. doi: 10.1186/s40168-016-0223-9.
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citation: Stapleton AE, Au-Yeung M, Hooton TM, Fredricks DN, Roberts PL, Czaja CA, Yarova-Yarovaya Y, Fiedler T, Cox M, Stamm WE. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis. 2011 May;52(10):1212-7. doi: 10.1093/cid/cir183. Epub 2011 Apr 14.
citation: Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1(Suppl 1):4680-7. doi: 10.1073/pnas.1002611107. Epub 2010 Jun 3.