Preterm LaborPhase 1NCT03992534
The FLIP-1 Study: Vaginal Lactobacillus Supplementation in Women at High Risk of Preterm Birth
A Phase 1 study testing LACTIN-V in people with Preterm Labor and Preterm Birth, run by Imperial College London at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women only
- Conditions the study is for
- Preterm Labor, Preterm Birth, Preterm Premature Rupture of Membrane
- What is being tested?
- LACTIN-V
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 16 Sep 2019to 1 Oct 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- HIV positive women
- Women who are unable to provide informed consent
- Women aged <18
- Women receiving antibiotic treatment within 1 week of recruitment
Trial locations and contacts
1 site in 1 country.
David MacIntyre, BSc PhD contact
United Kingdom1 site, 1 recruiting
- Recruiting
Institute of Reproductive Developmental Biology, Hammersmith Hospital
London, W12 0UQ
Erna Bayar, MBBS BSc (Hons) MSc FHEA, e.bayar@imperial.ac.uk
About this study
Official title: Feasibility, Safety, Tolerance and Assessment of LACTIN-V Use in a Cohort of Pregnant Women at Risk of Preterm Birth
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.
Read the 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.
- Conditions
- Preterm Labor, Preterm Birth, Preterm Premature Rupture of Membrane, Cervical Incompetence, Miscarriage in Second Trimester, Miscarriage in Third Trimester
- Being tested
- LACTIN-V
- Keywords
- Pregnancy, Preterm labour, Preterm delivery, Vaginal microbiome, Infection, Next generation sequencing, Lactobacillus
- Medical subject headings
- Obstetric Labor, Premature, Premature Birth, Preterm Premature Rupture of the Membranes, Uterine Cervical Incompetence, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LACTIN-VCombination product
Also called Lactobacillus crispatus
Vaginal supplementation with L. crispatus CTV-05.
| Study group | Role | What they receive |
|---|---|---|
| LACTIN-V | Experimental | 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. Receives: Combination Product: LACTIN-V |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2-4 years
Secondary outcomes (2)
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.
Measured: 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
Measured: 2-4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2019
- Study start16 Sep 2019
- Primary completion1 Oct 2021 (estimated)
- Study completion1 Oct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Preterm LaborStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College Healthcare NHS Trust
- Responsible party
- Sponsor
- Investigators
- Phillip Bennett, BSc PhD MD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03992534
- Sponsor's protocol ID
- 19QC5168
- Status last verified
- May 2020
- First submitted
- 1 May 2019
- Last updated
- 28 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes
Publications
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.
PubMed 25758319Brown 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.
PubMed 29361936Kindinger 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.
PubMed 28103952Kindinger 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.
PubMed 27488896Stapleton 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.
PubMed 21498386Ravel 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.
PubMed 20534435
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility, Safety, Tolerance and Assessment of LACTIN-V Use in a Cohort of Pregnant Women at Risk of Preterm Birth
- ClinicalTrials.gov ID
- NCT03992534
- Acronym / sponsor ID
- 19QC5168
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Imperial College Healthcare NHS Trust
- Study start
- 16 Sep 2019 (actual)
- Primary completion
- 1 Oct 2021 (estimated)
- Study completion
- 1 Oct 2021 (estimated)
- First posted
- 20 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LACTIN-V | Experimental | Combination Product: LACTIN-VName 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- HIV positive women
- Women who are unable to provide informed consent
- Women aged <18
- Women receiving antibiotic treatment within 1 week of recruitment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LACTIN-VAlso: Lactobacillus crispatusVaginal supplementation with L. crispatus CTV-05. | Combination product | LACTIN-V |
Primary outcome
The number of participants that demonstrate a change in vaginal colonisation during and following LACTIN-V use.
Time frame: 2-4 years
Microbiological effects of LACTIN-V by laboratory analysis, next generation sequencing
2 secondary outcomes
The number of participants with treatment related adverse events following LACTIN-V supplementation in pregnant women at high risk of preterm birth.
Time frame: 2-4 years
The number of patients using LACTIN-V that go on to experience preterm birth, PPROM or cervical shortening.
Time frame: 2-4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2020.
- Background: PubMed 25758319MacIntyre 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.
- Background: PubMed 29361936Brown 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.
- Background: PubMed 28103952Kindinger 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.
- Background: PubMed 27488896Kindinger 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.
- Background: PubMed 21498386Stapleton 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.
- Background: PubMed 20534435Ravel 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David MacIntyre, BSc PhD contact
Phillip Bennett, BSc PhD MD principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LACTIN-V in people with Preterm Labor and Preterm Birth, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Phillip Bennett, BSc PhD MD (+442075942176, p.bennett@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of participants that demonstrate a change in vaginal colonisation during and following LACTIN-V use. (time frame: 2-4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03992534, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2020; AzTrials last refreshed its copy on 7 Nov 2026.