The FLIP-1 Study: Vaginal Lactobacillus Supplementation in Women at High Risk of Preterm Birth

Preterm Birth Clinical Trial

Official title:

Feasibility, Safety, Tolerance and Assessment of LACTIN-V Use in a Cohort of Pregnant Women at Risk of Preterm Birth

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03992534
• Other study ID #: 19QC5168
• Status: Recruiting
• Phase: Phase 1
• Start date: September 16, 2019
• Est. completion date: October 1, 2021

Study information

• Verified date: May 2020
• Source: Imperial College London
• Contact: Phillip Bennett, BSc PhD MD
• Phone: +442075942176
• Email: p.bennett[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 1, 2021
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Abortion, Spontaneous
• Cervical Incompetence
• Fetal Membranes, Premature Rupture
• Miscarriage in Second Trimester
• Miscarriage in Third Trimester
• Obstetric Labor, Premature
• Premature Birth
• Preterm Birth
• Preterm Labor
• Preterm Premature Rupture of Membrane
• Rupture
• Uterine Cervical Incompetence

Intervention

Combination Product:
• LACTIN-V
Vaginal supplementation with L. crispatus CTV-05.

Locations

Country	Name	City	State
United Kingdom	Institute of Reproductive Developmental Biology, Hammersmith Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	Imperial College Healthcare NHS Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (6)

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. — View 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. — View Citation

Kindinger LM, MacIntyre DA, Lee YS, Marchesi JR, Smith A, McDonald JA, Terzidou V, Cook JR, Lees C, Israfil-Bayli F, Faiza Y, Toozs-Hobson P, Slack M, Cacciatore S, Holmes E, Nicholson JK, Teoh TG, Bennett PR. Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage. Sci Transl Med. 2016 Aug 3;8(350):350ra102. doi: 10.1126/scitranslmed.aag1026. — View 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. — View 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 1:4680-7. doi: 10.1073/pnas.1002611107. Epub 2010 Jun 3. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of participants that demonstrate a change in vaginal colonisation during and following LACTIN-V use.	Microbiological effects of LACTIN-V by laboratory analysis, next generation sequencing	2-4 years
Secondary	The number of participants with treatment related adverse events following LACTIN-V supplementation in pregnant women at high risk of preterm birth.	Participants will be asked about adverse events during clinical review and the safety profile will be recorded.	2-4 years
Secondary	The number of patients using LACTIN-V that go on to experience preterm birth, PPROM or cervical shortening.	Clinical outcomes of participants will be analysed, in accordance with colonisation results	2-4 years