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

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)

Study Overview

• Status: Unknown
• Conditions: Periodontitis and Pregnancy
• Intervention / Treatment: Dietary supplement: Probiotic; Other: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy, 70121
    • Not yet recruiting
    • Department of Pediatric. Università di Bari; Ospedale Pediatrico Giovanni XXIII
    • Contact: Flavia Indrio, PhD; Phone Number: +393292938421; Email: f.indrio@alice.it
    • Contact: Guisseppe Loverro, MD; Phone Number: +393292938421; Email: giuseppe.loverro@uniba.it
• Mexico
  • Tlalpan
    • Mexico city, Tlalpan, Mexico, 14080
      • Recruiting
      • Hospital General Dr. Manuel Gea González
      • Contact: Cesar D Nieto, MSc; Phone Number: 1246 525540003000; Email: cedav08@hotmail.com
      • Contact: Paola Juarez, MD; Phone Number: 1246 525540003000; Email: pao_8816@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; 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; 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.
Placebo Comparator: Placebo; 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; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Innovacion y Desarrollo de Estrategias en Salud
• Collaborators: University of Bari; BioGaia AB

Publications and helpful links

General 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.
• Staab 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.
• Harini 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.
• Slawik 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.
• Iniesta 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.
• Stensson 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.
• Toiviainen 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2017
• Primary Completion (Actual): June 30, 2019
• Study Completion (Anticipated): December 30, 2019

Study Registration Dates

• First Submitted: November 29, 2017
• First Submitted That Met QC Criteria: December 12, 2017
• First Posted (Actual): December 15, 2017

Study Record Updates

• Last Update Posted (Actual): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 27, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Periodontitis
• Other Study ID Numbers: CSUB0138

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No