Microbiome Alterations With Xylitol (MAX) in Pregnancy

NCT06329596 | Active Not Recruiting Phase 1

• 2 other identifiers: H-55146D43TW012274
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to understand if chewing xylitol-gum initiated before 20 weeks of pregnancy and continued until delivery affects the bacteria that are found in the oral and vaginal cavities, signs of inflammation within the gingiva of the oral cavity, the health of the tissues in the mouth (clinical parameters of periodontal disease) and placentae, and the bacteria in the mouth and gut of newborns among pregnant individuals in Malawi. In addition, we will evaluate the impact of xylitol-containing chewing gum use during pregnancy on the offsprings neurodevelopment at approximately 6- and 18-months corrected age.

Conditions

Dysbiosis; Inflammation Gum; Placenta-mediated Pregnancy Complications; Microbioata; Neurodevelopmental Changes (Childhood, Ageing)

Keywords

microbial alterations; xylitol; Malawi; infant neurodevelopment

Outcome Measures

Primary Outcomes (1)

• Periodontal disease at 28-30 weeks of pregnancy

  The investigators will create scaled periodontal disease score comprising of sum of scores for gingival bleeding (+1 if bleeding was present, per tooth), gingival pockets (+1 for pockets of 4-5 mm and +2 for 6 mm or deeper, per tooth), and loss of attachment (+1 for 4-5 mm loss, +2 for 6-8 mm, +3 for 9-11 mm, and +4 for 12 mm or more, per tooth with values recorded for index teeth) divided by the number of teeth present will be created for every dental visit. A score of \>0 will indicate presence of periodontal disease. The investigators will compare periodontal disease status at 28-30 weeks of pregnancy to that at enrolment.

  Enrolment and 28-30 weeks of pregnancy.

Secondary Outcomes (9)

• Periodontal disease at 6 weeks postpartum

  Enrolment and 6 weeks postpartum

• Alterations in the maternal oral microbiome communities

  Enrolment and at 28-30 weeks, delivery and 4-6 weeks after

• Alterations in the maternal vaginal microbiome communities

  Enrolment and at 28-30 weeks, delivery and 4-6 weeks after

• Inflammatory mediator changes in the maternal gingival crevicular fluid compared to changes in the placenta.

  Enrolment and at 28-30 weeks, and at delivery

• Alterations within the infants' oral microbiome communities

  4-6 weeks

Study Arms (2)

Xylitol gum

EXPERIMENTAL

Participants will receive 6.36grams of daily xylitol; Epic dental gum, 1.06 grams Xylitol per piece of gum; to chew two pieces for 5 minutes after meals, thrice a day.

Dietary Supplement: Xylitol gum

Sorbitol gum

PLACEBO COMPARATOR

Participants will receive Epic sorbitol-containing gum (0 grams xylitol/day); to chew two pieces for 5 minutes after meals, thrice a day.

Dietary Supplement: Sorbitol gum

Interventions

Xylitol gum DIETARY_SUPPLEMENT

Two pieces of xylitol gum after meals, thrice a day.

Also known as: Epic Xylitol gum

Xylitol gum

Sorbitol gum DIETARY_SUPPLEMENT

Two pieces of sorbitol gum after meals, thrice a day.

Sorbitol gum

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Able to provide informed consent. For those under 18 years of age, consent will additionally be sought from the parent or guardian.
• A singleton at \<20 weeks' gestation (based on ultrasound or best obstetric measurement)
• Planning to deliver at Area 25 health center.
• Willing to chew two pieces of gum thrice daily for 5 minutes after the morning, day and evening meals throughout pregnancy.
• Willing to undergo at least two dental exams including oral microbiota sampling at study enrolment \<20 weeks of pregnancy, 28-30 weeks, at delivery/within 48 hours and 4-6 weeks after giving birth.
• Willing to have at least two vaginal sampling at study enrolment \<20 weeks of pregnancy, 28-30 weeks, at delivery/within 48 hours and 4-6 weeks after giving birth.
• Able to speak Chichewa or English.
• Cognitively aware enough to be able to participate in the study.
• Willing to consent to all required aspects of protocol including allowing collection of placenta specimens, infant oral swab and meconium/stool sampling at birth/within 48 hours and 4-6 weeks after.

You may not qualify if:

• Those who upon screening and enrolment but dislike the taste of the gum and state they will not chew the gum throughout pregnancy.
• Gravidae with known or suspected non-viable pregnancy (including life threatening congenital anomalies such as cardiac, neurological or others).
• Pregnant individual has a life-threatening diagnosis such as cancer requiring treatment during pregnancy.
• Pregnant women with a known or suspected morbidly adherent placenta (such as placenta accrete, increta and percreta).

Sponsors & Collaborators

• University of Washington: collaborator
• Baylor College of Medicine Children's Foundation Malawi: collaborator
• Baylor College of Medicine: lead
• Fogarty International Center of the National Institute of Health: collaborator
• Thrasher Medical Research Foundation: collaborator
• Cure Within Reach: collaborator

Study Sites (1)

Area 25 Health Center

Lilongwe, Malawi

Location

Related Publications (12)

• Chen P, Hong F, Yu X. Prevalence of periodontal disease in pregnancy: A systematic review and meta-analysis. J Dent. 2022 Oct;125:104253. doi: 10.1016/j.jdent.2022.104253. Epub 2022 Aug 20.

  PMID: 35998741 RESULT

• Robinson JL, Johnson PM, Kister K, Yin MT, Chen J, Wadhwa S. Estrogen signaling impacts temporomandibular joint and periodontal disease pathology. Odontology. 2020 Apr;108(2):153-165. doi: 10.1007/s10266-019-00439-1. Epub 2019 Jul 3.

  PMID: 31270648 RESULT

• Alnasser BH, Alkhaldi NK, Alghamdi WK, Alghamdi FT. The Potential Association Between Periodontal Diseases and Adverse Pregnancy Outcomes in Pregnant Women: A Systematic Review of Randomized Clinical Trials. Cureus. 2023 Jan 1;15(1):e33216. doi: 10.7759/cureus.33216. eCollection 2023 Jan.

  PMID: 36733569 RESULT

• Bobetsis YA, Graziani F, Gursoy M, Madianos PN. Periodontal disease and adverse pregnancy outcomes. Periodontol 2000. 2020 Jun;83(1):154-174. doi: 10.1111/prd.12294.

  PMID: 32385871 RESULT

• Zhang Y, Feng W, Li J, Cui L, Chen ZJ. Periodontal Disease and Adverse Neonatal Outcomes: A Systematic Review and Meta-Analysis. Front Pediatr. 2022 May 4;10:799740. doi: 10.3389/fped.2022.799740. eCollection 2022.

  PMID: 35601423 RESULT

• Iheozor-Ejiofor Z, Middleton P, Esposito M, Glenny AM. Treating periodontal disease for preventing adverse birth outcomes in pregnant women. Cochrane Database Syst Rev. 2017 Jun 12;6(6):CD005297. doi: 10.1002/14651858.CD005297.pub3.

  PMID: 28605006 RESULT

• Soderling E, Pienihakkinen K. Effects of xylitol and erythritol consumption on mutans streptococci and the oral microbiota: a systematic review. Acta Odontol Scand. 2020 Nov;78(8):599-608. doi: 10.1080/00016357.2020.1788721. Epub 2020 Jul 7.

  PMID: 32633595 RESULT

• Marghalani AA, Guinto E, Phan M, Dhar V, Tinanoff N. Effectiveness of Xylitol in Reducing Dental Caries in Children. Pediatr Dent. 2017 Mar 15;39(2):103-110.

  PMID: 28390459 RESULT

• Gudnadottir U, Debelius JW, Du J, Hugerth LW, Danielsson H, Schuppe-Koistinen I, Fransson E, Brusselaers N. The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis. Sci Rep. 2022 May 13;12(1):7926. doi: 10.1038/s41598-022-12007-9.

  PMID: 35562576 RESULT

• Loimaranta V, Mazurel D, Deng D, Soderling E. Xylitol and erythritol inhibit real-time biofilm formation of Streptococcus mutans. BMC Microbiol. 2020 Jun 29;20(1):184. doi: 10.1186/s12866-020-01867-8.

  PMID: 32600259 RESULT

• Soderling E, Pienihakkinen K, Gursoy UK. Effects of sugar-free polyol chewing gums on gingival inflammation: a systematic review. Clin Oral Investig. 2022 Dec;26(12):6881-6891. doi: 10.1007/s00784-022-04729-x. Epub 2022 Oct 14.

  PMID: 36239787 RESULT

• Soderling E, Pienihakkinen K. Effects of xylitol chewing gum and candies on the accumulation of dental plaque: a systematic review. Clin Oral Investig. 2022 Jan;26(1):119-129. doi: 10.1007/s00784-021-04225-8. Epub 2021 Oct 22.

  PMID: 34677696 RESULT

MeSH Terms

Conditions

Dysbiosis; Gingivitis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Gingival Diseases; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Benjamin Shayo, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participants, data collectors (i.e. dental officers, study staff members, clinical officers), and data analysts will be blinded (triple-blinded) to group allocation throughout the study.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 26, 2024
• Study Start: June 13, 2024
• Primary Completion (Estimated): August 20, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 1 year after the study conclusion will the data become available and be available for approximately 10 years after study completion.
• Access Criteria: Investigators interested in the study data should contact the Study PI (Dr. Ben Shayo - Benjamin.shayo@bcm.edu) or study team members (i.e. Dr. Greg Valentine - gcvalent@uw.edu).

Locations

MA (1)