Abortion, SpontaneousPhase 2NCT04446572
Application of Lactobacillus Salivarius CECT5713 in Infertility of Unknown Origin
A Phase 2 study testing Lactobacillus salivarius CECT5713 in people with Abortion, Spontaneous and Abortion in First Trimester, run by Universidad Complutense de Madrid at 1 site in Spain.
Trial summary
In this study, we aimed to assess the cervicovaginal environment (pH, Nugent score, soluble immune factors and bacterial profile) in women with reproductive failure because of either repetitive abortion or infertility of unknown origin and compare it to that of healthy fertile women. Read more about this study
- Who is it for?
- Ages 33 to 41 years, women only
- Conditions the study is for
- Abortion, Spontaneous, Abortion in First Trimester, Infertility Unexplained
- What is being tested?
- Lactobacillus salivarius CECT5713
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteSpain
- Study dates
- 16 Oct 2018to 29 Nov 2019
- Phase
- Phase 2
- 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 33 to 41 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Recurrent miscarriage with three or more pregnancy losses during the first 12 weeks of pregnancy (RA group)
- Infertility (inability to conceive) despite being the recipients of ART for at least three times, including two cycles, at least, of in vitro fertilization (IVF) (INF group).
- Fertile women having at least two children after uncomplicated term pregnancies (Control group).
Who cannot join
- Antiphospholipid syndrome
- Hormonal therapy, antibiotics or probiotics in the 4 weeks previous to sampling.
- Lactose intolerance or cow's milk protein allergy (RA and INF groups)
Trial locations and contacts
1 site in 1 country.
Spain1 site
Dpt. Nutricion, Bromatologia y Tecnologia de los Alimentos
Madrid, 28040
About this study
Official title: Application of Lactobacillus Salivarius CECT5713 to Achieve Term Pregnancies in Women With Repetitive Abortion or Infertility of Unknown Origin by Microbiological and Immunological Modulation of the Vaginal Ecosystem
In this study, we aimed to assess the cervicovaginal environment (pH, Nugent score, soluble immune factors and bacterial profile) in women with reproductive failure because of either repetitive abortion or infertility of unknown origin and compare it to that of healthy fertile women. The second objective was to evaluate the ability of Lactobacillus salivarius CECT5713 to modulate such parameters and to increase pregnancy rates in women with reproductive failure. The administration of L. salivarius CECT5713 (~9 log10 colony-forming units (CFU)/day) for 6 months or until a diagnosis of pregnancy to women with reproductive failure resulted in an overall successful (term) pregnancy rate of 56%.
Read the detailed description
In this study, we aimed to assess the cervicovaginal environment (pH, Nugent score, soluble immune factors and bacterial profile) in women with reproductive failure because of either repetitive abortion or infertility of unknown origin and compare it to that of healthy fertile women. The second objective was to evaluate the ability of Lactobacillus salivarius CECT5713 to modulate such parameters and to increase pregnancy rates in women with reproductive failure. Vaginal pH and Nugent score were higher in women with reproductive failure than in fertile women. Differences were also noted regarding soluble immune factors transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF). Their concentrations in cervicovaginal lavage samples were reduced by about one-half in women with reproductive failure compared to fertile women. Lactobacilli were detected in a higher proportion, and at a higher concentration and having different species profile, in fertile women than in women with repetitive abortion or infertility. The study of the vaginal microbiome revealed that samples from fertile women were characterized by the high abundance of Lactobacillus sequences, while in about one third of samples from women with reproductive failure DNA from this genus was practically absent while there was an abundance of that of Gardnerella and Bifidobacterium. Lactobacillus salivarius CECT5713 seemed to be a suitable candidate to modulate the cervicovaginal microbiota because of its acidifying capacity, adhesion to vaginal cells and co-aggregation with vaginal pathogens. The administration of L. salivarius CECT5713 (~9 log10 CFU/day) for 6 months or until a diagnosis of pregnancy to women with reproductive failure resulted in an overall successful (term) pregnancy rate of 56%. In addition, the probiotic intervention modified significantly key microbiological, biochemical and immunological parameters in women who got pregnant being their post-intervention values similar or close to those of fertile women. The high concentrations of L. salivarius and the detection of L. salivarius DNA in vaginal samples confirmed that the probiotic was able to reach the vaginal mucosa. In conclusion, L. salivarius CECT5713 has proved to be a good candidate to improve reproductive success in women with reproductive failure.
- Being tested
- Lactobacillus salivarius CECT5713
- Keywords
- Infertility, Abortion
- Medical subject headings
- Abortion, Spontaneous, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus salivarius CECT5713Biological
Starting at day 0, women of the RA and INF groups consumed (oral route) a daily sachet with ~50 mg of freeze-dried probiotic (~9 log10 CFU of L. salivarius CECT5713) for 6 months or until a diagnosis of pregnancy (whatever happened first).
| Study group | Role | What they receive |
|---|---|---|
| Repetitive Abortion (RA) group | Experimental | Starting at day 0, women of the RA (n=21) group consumed (oral route) a daily sachet with ~50 mg of freeze-dried probiotic (~9 log10 CFU of L. salivarius CECT5713) for 6 months or until a diagnosis of pregnancy (whatever happened first). Receives: Biological: Lactobacillus salivarius CECT5713 |
| Infertility (INF) group | Experimental | Starting at day 0, women of the INF group (n=23) consumed (oral route) a daily sachet with ~50 mg of freeze-dried probiotic (~9 log10 CFU of L. salivarius CECT5713) for 6 months or until a diagnosis of pregnancy (whatever happened first). Receives: Biological: Lactobacillus salivarius CECT5713 |
| Control group | No intervention | The control group (n = 14) included fertile women having at least two children after uncomplicated term pregnancies. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pregnancies and successful pregnancies
Total number of pregnancies and number of pregnancies with delivery of a healthy baby
Measured: 6 months
Secondary outcomes (2)
Modification of the vaginal microbiota
Variation in the concentration of lactobacilli and other bacteria in cervicovaginal lavage samples
Measured: 6 months
Vaginal immunomodulation
Variation in the concentration of TGF-β and VEGF in cervicovaginal lavage
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2020
- Study start16 Oct 2018
- Primary completion29 Nov 2019
- Study completion29 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Abortion, SpontaneousStudies of the same condition, open and under way.
- More trials run by Universidad Complutense de MadridThe 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 2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Volunteers were classified into 3 groups. All women in the RA group (n = 21) had a history of recurrent miscarriage with three or more pregnancy losses during the first 12 weeks of pregnancy. All women of the INF group (n = 23) had a history of infertility (inability to conceive) despite being the recipients of assisted-reproduction techniques (ART) for at least three times, including two cycles, at least, of in vitro fertilization (IVF). Finally, the control group (n = 14) included fertile women having at least two children after uncomplicated term pregnancies. Starting at day 0, women of the RA and INF groups consumed (oral route) a daily sachet with \~50 mg of freeze-dried probiotic (\~9 log10 CFU of L. salivarius CECT5713) for 6 months or until a diagnosis of pregnancy (whatever happened first).
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universidad Complutense de Madrid
- Sponsor type
- University, hospital or other
- Collaborators
- Bisearch Life, Centro de Diagnóstico Médico. Ayuntamiento de Madrid.
- Responsible party
- Principal investigator, Juan M. Rodríguez, Universidad Complutense de Madrid
- Investigators
- Juan M Rodríguez, PhD, Principal investigator, Complutense University Madrid
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04446572
- Sponsor's protocol ID
- PREPROBIFERT01
- Status last verified
- Jun 2020
- First submitted
- 22 Jun 2020
- Last updated
- 26 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Global and individual microbiological and immunological data will be available to other researchers once the study is published.
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Application of Lactobacillus Salivarius CECT5713 to Achieve Term Pregnancies in Women With Repetitive Abortion or Infertility of Unknown Origin by Microbiological and Immunological Modulation of the Vaginal Ecosystem
- ClinicalTrials.gov ID
- NCT04446572
- Acronym / sponsor ID
- PREPROBIFERT01
- Keywords
- Infertility, Abortion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Universidad Complutense de MadridUniversity, hospital or other
- Collaborators
- Bisearch Life, Centro de Diagnóstico Médico. Ayuntamiento de Madrid.
- Study start
- 16 Oct 2018 (actual)
- Primary completion
- 29 Nov 2019 (actual)
- Study completion
- 29 Nov 2019 (actual)
- First posted
- 25 Jun 2020 (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.
In this study, we aimed to assess the cervicovaginal environment (pH, Nugent score, soluble immune factors and bacterial profile) in women with reproductive failure because of either repetitive abortion or infertility of unknown origin and compare it to that of healthy fertile women. The second objective was to evaluate the ability of Lactobacillus salivarius CECT5713 to modulate such parameters and to increase pregnancy rates in women with reproductive failure. The administration of L. salivarius CECT5713 (~9 log10 colony-forming units (CFU)/day) for 6 months or until a diagnosis of pregnancy to women with reproductive failure resulted in an overall successful (term) pregnancy rate of 56%.
Detailed description
In this study, we aimed to assess the cervicovaginal environment (pH, Nugent score, soluble immune factors and bacterial profile) in women with reproductive failure because of either repetitive abortion or infertility of unknown origin and compare it to that of healthy fertile women. The second objective was to evaluate the ability of Lactobacillus salivarius CECT5713 to modulate such parameters and to increase pregnancy rates in women with reproductive failure. Vaginal pH and Nugent score were higher in women with reproductive failure than in fertile women. Differences were also noted regarding soluble immune factors transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF). Their concentrations in cervicovaginal lavage samples were reduced by about one-half in women with reproductive failure compared to fertile women. Lactobacilli were detected in a higher proportion, and at a higher concentration and having different species profile, in fertile women than in women with repetitive abortion or infertility. The study of the vaginal microbiome revealed that samples from fertile women were characterized by the high abundance of Lactobacillus sequences, while in about one third of samples from women with reproductive failure DNA from this genus was practically absent while there was an abundance of that of Gardnerella and Bifidobacterium. Lactobacillus salivarius CECT5713 seemed to be a suitable candidate to modulate the cervicovaginal microbiota because of its acidifying capacity, adhesion to vaginal cells and co-aggregation with vaginal pathogens. The administration of L. salivarius CECT5713 (~9 log10 CFU/day) for 6 months or until a diagnosis of pregnancy to women with reproductive failure resulted in an overall successful (term) pregnancy rate of 56%. In addition, the probiotic intervention modified significantly key microbiological, biochemical and immunological parameters in women who got pregnant being their post-intervention values similar or close to those of fertile women. The high concentrations of L. salivarius and the detection of L. salivarius DNA in vaginal samples confirmed that the probiotic was able to reach the vaginal mucosa. In conclusion, L. salivarius CECT5713 has proved to be a good candidate to improve reproductive success in women with reproductive failure.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Volunteers were classified into 3 groups. All women in the RA group (n = 21) had a history of recurrent miscarriage with three or more pregnancy losses during the first 12 weeks of pregnancy. All women of the INF group (n = 23) had a history of infertility (inability to conceive) despite being the recipients of assisted-reproduction techniques (ART) for at least three times, including two cycles, at least, of in vitro fertilization (IVF). Finally, the control group (n = 14) included fertile women having at least two children after uncomplicated term pregnancies. Starting at day 0, women of the RA and INF groups consumed (oral route) a daily sachet with ~50 mg of freeze-dried probiotic (~9 log10 CFU of L. salivarius CECT5713) for 6 months or until a diagnosis of pregnancy (whatever happened first).
| Arm | Type | Receives |
|---|---|---|
| Repetitive Abortion (RA) group | Experimental | Biological: Lactobacillus salivarius CECT5713Starting at day 0, women of the RA (n=21) group consumed (oral route) a daily sachet with ~50 mg of freeze-dried probiotic (~9 log10 CFU of L. salivarius CECT5713) for 6 months or until a diagnosis of pregnancy (whatever happened first). |
| Infertility (INF) group | Experimental | Biological: Lactobacillus salivarius CECT5713Starting at day 0, women of the INF group (n=23) consumed (oral route) a daily sachet with ~50 mg of freeze-dried probiotic (~9 log10 CFU of L. salivarius CECT5713) for 6 months or until a diagnosis of pregnancy (whatever happened first). |
| Control group | No intervention | –The control group (n = 14) included fertile women having at least two children after uncomplicated term pregnancies. |
Who may qualify
- Ages
- 33 to 41 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Recurrent miscarriage with three or more pregnancy losses during the first 12 weeks of pregnancy (RA group)
- Infertility (inability to conceive) despite being the recipients of ART for at least three times, including two cycles, at least, of in vitro fertilization (IVF) (INF group).
- Fertile women having at least two children after uncomplicated term pregnancies (Control group).
Key exclusion criteria (3 listed)
- Antiphospholipid syndrome
- Hormonal therapy, antibiotics or probiotics in the 4 weeks previous to sampling.
- Lactose intolerance or cow's milk protein allergy (RA and INF groups)
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 |
|---|---|---|
| Lactobacillus salivarius CECT5713Starting at day 0, women of the RA and INF groups consumed (oral route) a daily sachet with ~50 mg of freeze-dried probiotic (~9 log10 CFU of L. salivarius CECT5713) for 6 months or until a diagnosis of pregnancy (whatever happened first). | Biological | Infertility (INF) group, Repetitive Abortion (RA) group |
Primary outcome
Pregnancies and successful pregnancies
Time frame: 6 months
Total number of pregnancies and number of pregnancies with delivery of a healthy baby
2 secondary outcomes
Modification of the vaginal microbiota
Time frame: 6 months
Vaginal immunomodulation
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2020.
- Individual participant dataSharing planned: Yes. Global and individual microbiological and immunological data will be available to other researchers once the study is published.
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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.
Juan M Rodríguez, PhD principal investigator
Complutense University Madrid
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lactobacillus salivarius CECT5713 in people with Abortion, Spontaneous and Abortion in First Trimester, run by Universidad Complutense de Madrid at 1 site in Spain.
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 3 inclusion and 3 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: finished, as of the sponsor's last update on 26 Jun 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 Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pregnancies and successful pregnancies (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Jun 2020.