Periodontitis and PregnancyNCT03375125
L. Reuteri ATCC PTA 5289 + L. Reuteri DSM 17938 in Pregnant Women
A study testing Probiotic in people with Periodontitis and Pregnancy, run by Innovacion y Desarrollo de Estrategias en Salud at 2 sites in 2 countries.
Trial summary
Randomized controlled tril to evaluate the safety and efficacy for the combination of L. reuteri ATCC PTA 5289 \& L. reuteri DSM 17938 in pregnant women with periodontitis and/or gingivits to improve oral health and at the same time reduce the risk for prematurity or intrauterine growth retardation (IUGR). Read more about this study
- Who is it for?
- Ages 15 to 40 years, women only
- Conditions the study is for
- Periodontitis and Pregnancy
- What is being tested?
- Probiotic
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 20 Dec 2017to 30 Dec 2019
- Phase
- Interventional
- 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 15 to 40 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Healthy pregnant women
- Age (Italy: 18-40 years; Mexico: 15-40 years)
- Gestational week (Mexico: >8 weeks and 16 weeks; Italy: >8 weeks and 12 weeks)
- Mild to Severe Gingival and Periodontal disease verified by dentist using Lobene Modified Gingival Index, Plaque Index, Gingival Bleeding Index, probing pocket depth (PPD) and clinical attachment level (CAL)
- Signed Informed consent
Who cannot join
- Pathologic pregnancy (except for preeclampsia and/or bacteriuria)
- Severe obesity (Body Mass Index>35)
- Use of any product containing probiotics 2 weeks before randomization
- Use of any product containing chlorhexidine 2 weeks before randomization
- Antibiotic therapy within 2 weeks before randomization
- Known allergies towards the ingredients of the experimental product
- Inability to comprehend to the study protocol
- Systemic diseases differnt that periodontal disease
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Italy1 site, 1 recruiting
- Not yet recruiting
Department of Pediatric. Università di Bari; Ospedale Pediatrico Giovanni XXIII
Bari, 70121
Flavia Indrio, PhD, +393292938421, f.indrio@alice.it
Guisseppe Loverro, MD, +393292938421, giuseppe.loverro@uniba.it
Mexico1 site, 1 recruiting
- Recruiting
Hospital General Dr. Manuel Gea Gonzalez
Mexico City, Tlalpan, 14080
Cesar D Nieto, MSc, 525540003000 ext. 1246, cedav08@hotmail.com
Paola Juarez, MD, 525540003000 ext. 1246, pao_8816@hotmail.com
About this study
Official title: Safety and Efficacy of L. Reuteri ATCC PTA 5289 & L. Reuteri DSM 17938 in Pregnant Women to Improve Oral Health and Reduce the Risk for Prematurity or Intrauterine Growth Retardation (IUGR)
Randomized controlled tril to evaluate the safety and efficacy for the combination of L. reuteri ATCC PTA 5289 \& L. reuteri DSM 17938 in pregnant women with periodontitis and/or gingivits to improve oral health and at the same time reduce the risk for prematurity or intrauterine growth retardation (IUGR).
Women in this study wil receive L. reuteri Prodentis (L. reuteri DSM 17938 \& L. reuteri ATCC PTA 5289 ) at a dose of 2x10^8 Colony Forming Units (CFU). One lozenges is to be taken twice per day (one in the morning and one in the afternoon) giving a total daily dose of at least 4x108 CFU/day since randomization until delivery. The control group will receive placebo lozenges which contains identical ingredients except for lacking the bacteria. One lozenges is to be taken twice per day (one in the morning and one in the afternoon. The study product will be kept refrigerated (+20 - +80 C)
Read the detailed description
Rationale. Gingivitis and periodontitis represent highly prevalent oral pathologies in pregnant women. The physiological, immunological and endocrine changes imposed by pregnancy are associated with a greater predisposition for the development of gingivitis. Considering the potential association between the presence of gingivitis and the development of complications during pregnancy and the time of delivery (preeclampsia, preterm, IUGRs), it is important to evaluate the impact of early administration of a mixture of lactobacillus on improved health oral status, and at the same time assessing the effect on risk reduction of prematurity and/or IUGRs.
For primary outcome the investigators will evaluate the changes along the study in the oral health status evaluated through a composite of Modified Gingival Index (Lobene) + Plaque Index (Silnes and Loe) + Gingival Bleeding Index + Probing pocket depth (PPD) and Clinical attachment level (CAL).
For secondary outcomes the investigators will evaluate rate of prematurity and or Intrauterine growth retardation; changes in mother salivary markers of systemic inflammation; profile of inflammosome in placenta and new born cord blood; lactobacilli, bifidobacteria and streptococcus profile in vagina by RT-PCR (specific primers); changes during the study for oral microbiome Intervention group wil receive L. reuteri Prodentis (L. reuteri DSM 17938 \& L. reuteri ATCC PTA 5289 ) at a dose of 2x10^8 Colony Forming Units (CFU). One lozenges is to be taken twice per day (one in the morning and one in the afternoon) giving a total daily dose of at least 4x108 CFU/day since randomization until delivery.
The control group will receive placebo lozenges which contains identical ingredients except for lacking the bacteria. One lozenges is to be taken twice per day (one in the morning and one in the afternoon. The study product will be kept refrigerated (+20 - +80 C)
- Conditions
- Periodontitis and Pregnancy
- Being tested
- Probiotic, Placebo
- Medical subject headings
- Periodontitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticDietary supplement
- reuteri DSM 17938 \& L. reuteri ATCC PTA 5289 ) will be given at a dose of 2x10^8 Colony Forming Units (CFU). One lozenges is to be taken twice per day (one in the morning and one in the afternoon) giving a total daily dose of at least 4x108 CFU/day.
PlaceboOther
Placebo will have identical appearance, taste, and flavor, except for lacking the bacteria. One lozenges will be taken twice per day (one in the morning and one in the afternoon)
| Study group | Role | What they receive |
|---|---|---|
| Probiotic | Experimental | L. reuteri DSM 17938 + L. reuteri ATCC PTA 5289), dose of 2x10^8 Colony Forming Units (CFU). One lozenges will be taken twice per day (one in the morning and one in the afternoon) giving a total daily dose of at least 4x108 CFU/day Receives: Dietary Supplement: Probiotic |
| Placebo | Placebo comparator | Placebo will have identical appearance, taste, and flavor, except for lacking the bacteria. One lozenges will be taken twice per day (one in the morning and one in the afternoon) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of periodontal disease
Changes along the study in periodontal disease evaluated through Modified Gingival Index
Measured: 6 months
Secondary outcomes (6)
Prematurity risk reduction
Rate of prematurity at moment of delivery
Measured: At delivery
Mother Inflammosome profile
Changes in salivary biomarkers of inflammation
Measured: 6 months
Placental Inflammosome
Profile of cytokines measured in placenta at delivery
Measured: At delivery
Changes in vaginal microbiome
Measurement of vaginal lactobacilli, bifidobacteria and streptococcus microbiome by RT-PCR
Measured: 6 months
Intrauterine growth retardation (IUGR) risj reduction
Rate of Intrauterine growth retardation (IUGR) at delivery
Measured: At delivery
Newborn cord blood inflammosome
Profile of cytokines measured in new-born cord blood at delivery
Measured: At delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2017
- Study start20 Dec 2017
- Primary completion30 Jun 2019
- Study completion30 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Periodontitis and PregnancyStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trial, double blind allocation concealment, parallel assignment
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Innovacion y Desarrollo de Estrategias en Salud
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bari, BioGaia AB
- Responsible party
- Principal investigator, Pedro Gutierrez Castrellon, Innovacion y Desarrollo de Estrategias en Salud
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03375125
- Sponsor's protocol ID
- CSUB0138
- Status last verified
- Jul 2019
- First submitted
- 29 Nov 2017
- Last updated
- 30 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson A, Sinkiewicz G. Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri. Swed Dent J. 2006;30(2):55-60.
PubMed 16878680Staab B, Eick S, Knofler G, Jentsch H. The influence of a probiotic milk drink on the development of gingivitis: a pilot study. J Clin Periodontol. 2009 Oct;36(10):850-6. doi: 10.1111/j.1600-051X.2009.01459.x. Epub 2009 Aug 12.
PubMed 19682173Harini PM, Anegundi RT. Efficacy of a probiotic and chlorhexidine mouth rinses: a short-term clinical study. J Indian Soc Pedod Prev Dent. 2010 Jul-Sep;28(3):179-82. doi: 10.4103/0970-4388.73799.
PubMed 21157050Slawik S, Staufenbiel I, Schilke R, Nicksch S, Weinspach K, Stiesch M, Eberhard J. Probiotics affect the clinical inflammatory parameters of experimental gingivitis in humans. Eur J Clin Nutr. 2011 Jul;65(7):857-63. doi: 10.1038/ejcn.2011.45. Epub 2011 Mar 30.
PubMed 21448219Iniesta M, Herrera D, Montero E, Zurbriggen M, Matos AR, Marin MJ, Sanchez-Beltran MC, Llama-Palacio A, Sanz M. Probiotic effects of orally administered Lactobacillus reuteri-containing tablets on the subgingival and salivary microbiota in patients with gingivitis. A randomized clinical trial. J Clin Periodontol. 2012 Aug;39(8):736-44. doi: 10.1111/j.1600-051X.2012.01914.x. Epub 2012 Jun 13.
PubMed 22694350Stensson M, Koch G, Coric S, Abrahamsson TR, Jenmalm MC, Birkhed D, Wendt LK. Oral administration of Lactobacillus reuteri during the first year of life reduces caries prevalence in the primary dentition at 9 years of age. Caries Res. 2014;48(2):111-7. doi: 10.1159/000354412. Epub 2013 Nov 29.
PubMed 24296746Toiviainen A, Jalasvuori H, Lahti E, Gursoy U, Salminen S, Fontana M, Flannagan S, Eckert G, Kokaras A, Paster B, Soderling E. Impact of orally administered lozenges with Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 on the number of salivary mutans streptococci, amount of plaque, gingival inflammation and the oral microbiome in healthy adults. Clin Oral Investig. 2015 Jan;19(1):77-83. doi: 10.1007/s00784-014-1221-6. Epub 2014 Mar 18.
PubMed 24638207
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of L. Reuteri ATCC PTA 5289 & L. Reuteri DSM 17938 in Pregnant Women to Improve Oral Health and Reduce the Risk for Prematurity or Intrauterine Growth Retardation (IUGR)
- ClinicalTrials.gov ID
- NCT03375125
- Acronym / sponsor ID
- CSUB0138
- Conditions
- Periodontitis and Pregnancy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Innovacion y Desarrollo de Estrategias en SaludUniversity, hospital or other
- Collaborators
- University of Bari, BioGaia AB
- Study start
- 20 Dec 2017 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 30 Dec 2019 (estimated)
- First posted
- 15 Dec 2017 (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.
Randomized controlled tril to evaluate the safety and efficacy for the combination of L. reuteri ATCC PTA 5289 \& L. reuteri DSM 17938 in pregnant women with periodontitis and/or gingivits to improve oral health and at the same time reduce the risk for prematurity or intrauterine growth retardation (IUGR).
Women in this study wil receive L. reuteri Prodentis (L. reuteri DSM 17938 \& L. reuteri ATCC PTA 5289 ) at a dose of 2x10^8 Colony Forming Units (CFU). One lozenges is to be taken twice per day (one in the morning and one in the afternoon) giving a total daily dose of at least 4x108 CFU/day since randomization until delivery. The control group will receive placebo lozenges which contains identical ingredients except for lacking the bacteria. One lozenges is to be taken twice per day (one in the morning and one in the afternoon. The study product will be kept refrigerated (+20 - +80 C)
Detailed description
Rationale. Gingivitis and periodontitis represent highly prevalent oral pathologies in pregnant women. The physiological, immunological and endocrine changes imposed by pregnancy are associated with a greater predisposition for the development of gingivitis. Considering the potential association between the presence of gingivitis and the development of complications during pregnancy and the time of delivery (preeclampsia, preterm, IUGRs), it is important to evaluate the impact of early administration of a mixture of lactobacillus on improved health oral status, and at the same time assessing the effect on risk reduction of prematurity and/or IUGRs.
For primary outcome the investigators will evaluate the changes along the study in the oral health status evaluated through a composite of Modified Gingival Index (Lobene) + Plaque Index (Silnes and Loe) + Gingival Bleeding Index + Probing pocket depth (PPD) and Clinical attachment level (CAL).
For secondary outcomes the investigators will evaluate rate of prematurity and or Intrauterine growth retardation; changes in mother salivary markers of systemic inflammation; profile of inflammosome in placenta and new born cord blood; lactobacilli, bifidobacteria and streptococcus profile in vagina by RT-PCR (specific primers); changes during the study for oral microbiome Intervention group wil receive L. reuteri Prodentis (L. reuteri DSM 17938 \& L. reuteri ATCC PTA 5289 ) at a dose of 2x10^8 Colony Forming Units (CFU). One lozenges is to be taken twice per day (one in the morning and one in the afternoon) giving a total daily dose of at least 4x108 CFU/day since randomization until delivery.
The control group will receive placebo lozenges which contains identical ingredients except for lacking the bacteria. One lozenges is to be taken twice per day (one in the morning and one in the afternoon. The study product will be kept refrigerated (+20 - +80 C)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized controlled trial, double blind allocation concealment, parallel assignment
| Arm | Type | Receives |
|---|---|---|
| Probiotic | Experimental | Dietary Supplement: ProbioticL. reuteri DSM 17938 + L. reuteri ATCC PTA 5289), dose of 2x10^8 Colony Forming Units (CFU). One lozenges will be taken twice per day (one in the morning and one in the afternoon) giving a total daily dose of at least 4x108 CFU/day |
| Placebo | Placebo comparator | Other: PlaceboPlacebo will have identical appearance, taste, and flavor, except for lacking the bacteria. One lozenges will be taken twice per day (one in the morning and one in the afternoon) |
Who may qualify
- Ages
- 15 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Healthy pregnant women
- Age (Italy: 18-40 years; Mexico: 15-40 years)
- Gestational week (Mexico: >8 weeks and 16 weeks; Italy: >8 weeks and 12 weeks)
- Mild to Severe Gingival and Periodontal disease verified by dentist using Lobene Modified Gingival Index, Plaque Index, Gingival Bleeding Index, probing pocket depth (PPD) and clinical attachment level (CAL)
- Signed Informed consent
Key exclusion criteria (8 listed)
- Pathologic pregnancy (except for preeclampsia and/or bacteriuria)
- Severe obesity (Body Mass Index>35)
- Use of any product containing probiotics 2 weeks before randomization
- Use of any product containing chlorhexidine 2 weeks before randomization
- Antibiotic therapy within 2 weeks before randomization
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 |
|---|---|---|
| ProbioticL. reuteri DSM 17938 \& L. reuteri ATCC PTA 5289 ) will be given at a dose of 2x10^8 Colony Forming Units (CFU). One lozenges is to be taken twice per day (one in the morning and one in the afternoon) giving a total daily dose of at least 4x108 CFU/day. | Dietary supplement | Probiotic |
| PlaceboPlacebo will have identical appearance, taste, and flavor, except for lacking the bacteria. One lozenges will be taken twice per day (one in the morning and one in the afternoon) | Other | Placebo |
Primary outcome
Improvement of periodontal disease
Time frame: 6 months
Changes along the study in periodontal disease evaluated through Modified Gingival Index
6 secondary outcomes
Prematurity risk reduction
Time frame: At delivery
Mother Inflammosome profile
Time frame: 6 months
Placental Inflammosome
Time frame: At delivery
Changes in vaginal microbiome
Time frame: 6 months
Intrauterine growth retardation (IUGR) risj reduction
Time frame: At delivery
Newborn cord blood inflammosome
Time frame: At delivery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
- Results publication: PubMed 16878680Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson A, Sinkiewicz G. Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri. Swed Dent J. 2006;30(2):55-60.
- Results publication: PubMed 19682173Staab B, Eick S, Knofler G, Jentsch H. The influence of a probiotic milk drink on the development of gingivitis: a pilot study. J Clin Periodontol. 2009 Oct;36(10):850-6. doi: 10.1111/j.1600-051X.2009.01459.x. Epub 2009 Aug 12.
- Results publication: PubMed 21157050Harini PM, Anegundi RT. Efficacy of a probiotic and chlorhexidine mouth rinses: a short-term clinical study. J Indian Soc Pedod Prev Dent. 2010 Jul-Sep;28(3):179-82. doi: 10.4103/0970-4388.73799.
- Results publication: PubMed 21448219Slawik S, Staufenbiel I, Schilke R, Nicksch S, Weinspach K, Stiesch M, Eberhard J. Probiotics affect the clinical inflammatory parameters of experimental gingivitis in humans. Eur J Clin Nutr. 2011 Jul;65(7):857-63. doi: 10.1038/ejcn.2011.45. Epub 2011 Mar 30.
- Results publication: PubMed 22694350Iniesta M, Herrera D, Montero E, Zurbriggen M, Matos AR, Marin MJ, Sanchez-Beltran MC, Llama-Palacio A, Sanz M. Probiotic effects of orally administered Lactobacillus reuteri-containing tablets on the subgingival and salivary microbiota in patients with gingivitis. A randomized clinical trial. J Clin Periodontol. 2012 Aug;39(8):736-44. doi: 10.1111/j.1600-051X.2012.01914.x. Epub 2012 Jun 13.
- Results publication: PubMed 24296746Stensson M, Koch G, Coric S, Abrahamsson TR, Jenmalm MC, Birkhed D, Wendt LK. Oral administration of Lactobacillus reuteri during the first year of life reduces caries prevalence in the primary dentition at 9 years of age. Caries Res. 2014;48(2):111-7. doi: 10.1159/000354412. Epub 2013 Nov 29.
- Results publication: PubMed 24638207Toiviainen A, Jalasvuori H, Lahti E, Gursoy U, Salminen S, Fontana M, Flannagan S, Eckert G, Kokaras A, Paster B, Soderling E. Impact of orally administered lozenges with Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 on the number of salivary mutans streptococci, amount of plaque, gingival inflammation and the oral microbiome in healthy adults. Clin Oral Investig. 2015 Jan;19(1):77-83. doi: 10.1007/s00784-014-1221-6. Epub 2014 Mar 18.
- Individual participant dataSharing planned: No
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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.
Department of Pediatric. Università di Bari; Ospedale Pediatrico Giovanni XXIII
Bari, Italy
Hospital General Dr. Manuel Gea Gonzalez
Mexico City, Mexico
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic in people with Periodontitis and Pregnancy, run by Innovacion y Desarrollo de Estrategias en Salud at 2 sites in 2 countries.
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 8 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 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy, Mexico. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement of periodontal disease (time frame: 6 months). 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 NCT03375125, which also lists 7 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 30 Jul 2019.