L. Reuteri ATCC PTA 5289 + L. Reuteri DSM 17938 in Pregnant Women

Study Overview
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Brief Summary
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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
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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)

Official Title
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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)

Conditions
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Periodontitis and Pregnancy

Intervention / Treatment
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* Dietary Supplement: Probiotic
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial, double blind allocation concealment, parallel assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>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 | Dietary Supplement: Probiotic<br>* L. 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.<br>|
| Placebo Comparator: Placebo<br>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) | Other: Placebo<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of periodontal disease | Changes along the study in periodontal disease evaluated through Modified Gingival Index | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prematurity risk reduction | Rate of prematurity at moment of delivery | At delivery | 
| Mother Inflammosome profile | Changes in salivary biomarkers of inflammation | 6 months | 
| Placental Inflammosome | Profile of cytokines measured in placenta at delivery | At delivery | 
| Changes in vaginal microbiome | Measurement of vaginal lactobacilli, bifidobacteria and streptococcus microbiome by RT-PCR | 6 months | 
| Intrauterine growth retardation (IUGR) risj reduction | Rate of Intrauterine growth retardation (IUGR) at delivery | At delivery | 
| Newborn cord blood inflammosome | Profile of cytokines measured in new-born cord blood at delivery | At delivery |