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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Preterm Labor, Preterm Birth, Preterm Premature Rupture of Membrane, Cervical Incompetence, Miscarriage in Second Trimester, Miscarriage in Third Trimester

Intervention / Treatment
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* Combination Product: LACTIN-V


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LACTIN-V<br>Name of Product: LACTIN-V (Lactobacillus crispatus CTV-05) Dosage: LACTINV is a powder formulation of Lactobacillus crispatus CTV-05 provided in a prefilled vaginal applicator at a dose of 2 x 10^9 CFU of L. crispatus CTV-05. Route of Administration: LACTIN-V powder is administered vaginally using a specially designed applicator. Formulation: LACTIN-V is supplied as a pre-filled, single-use applicator. Each applicator contains LACTIN-V powder at a dose of 2 x 10^9 CFU. The LACTIN-V powder formulation contains L. crispatus CTV-05 and a preservation matrix containing inactive excipients of non-animal origin. | Combination Product: LACTIN-V<br>* Vaginal supplementation with L. crispatus CTV-05.<br>* Other names: Lactobacillus crispatus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy, Preterm labour, Preterm delivery, Vaginal microbiome, Infection, Next generation sequencing, Lactobacillus