Microbiome Alterations With Xylitol (MAX) in Pregnancy

Dysbiosis Clinical Trial

— MAX  

Official title:

Periodontal Disease and Alterations in the Oral and Vaginal Microbiome Communities Among Gravidae Chewing Xylitol-gum in Malawi: Microbiome Alterations With Xylitol (MAX) in Pregnancy Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06329596
• Other study ID #: H-55146
• Secondary ID: D43TW012274
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 13, 2024
• Est. completion date: March 31, 2026

Study information

• Verified date: May 2024
• Source: Baylor College of Medicine
• Contact: Benjamin Shayo, MD
• Phone: +265980888996
• Email: benjamin.shayo[@]bcm.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 the bacteria in the mouth and gut of newborns among pregnant individuals in Malawi.

Description:

After consenting to the study, pregnant participants who have a singleton gestation and are <20 weeks' gestation will be randomised into either the intervention arm ( 6.36grams of daily xylitol; Epic dental gum, 1.06 grams Xylitol per piece of gum; chew two pieces for 5 minutes after meals, thrice a day) or the placebo control arm (Sorbitol Gum base; Epic sorbitol-containing gum, 0 grams/day of xylitol; chew two pieces for 5 minutes after meals, thrice a day) by randomly picking from a group of opaque, sealed envelopes containing group allocation. The participants will also undergo a dental assessment and sampling, and vaginal sampling at enrolment, 28- 30 weeks of pregnancy, at birth - 48 hours and 4-6 weeks after birth. In addition, placental specimens will be obtained at the time of delivery, and stored in a biobank for future analyses. The investigators will also obtain oral and meconium (and stool at 4-6 weeks) samples of their newborns at birth and 4-6 weeks after birth.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 12 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Related Conditions & MeSH terms

• Dysbiosis
• Gingivitis
• Inflammation
• Inflammation Gum

Intervention

Dietary Supplement:
• Xylitol gum
Two pieces of xylitol gum after meals, thrice a day.
• Sorbitol gum
Two pieces of sorbitol gum after meals, thrice a day.

Locations

Country	Name	City	State
Malawi	Area 25 Health Center	Lilongwe

Sponsors (4)

Lead Sponsor	Collaborator
Baylor College of Medicine	Baylor College of Medicine Children's Foundation Malawi, Fogarty International Center of the National Institute of Health, University of Washington

Country where clinical trial is conducted

Malawi, 

References & Publications (12)

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/c — View Citation

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. — View Citation

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. — View Citation

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/ — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Periodontal disease at 6 weeks postpartum	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 6 weeks postpartum to that at enrolment.	Enrolment and 6 weeks postpartum
Secondary	Alterations in the maternal oral microbiome communities delivery	Using 16S rRNA sequencing to assess strain level changes in sub gingival plaque composition within and between those exposed to xylitol and placebo gum using exact amplicon sequence variants.	Enrolment and at 28-30 weeks, delivery and 4-6 weeks after
Secondary	Alterations in the maternal vaginal microbiome communities	Using 16S rRNA sequencing to assess strain level changes in the vaginal microbiome at the vaginal introitus and posterior fornix. The investigators will compare compositional differences between sites in relationship to treatment	Enrolment and at 28-30 weeks, delivery and 4-6 weeks after
Secondary	Inflammatory mediator changes in the maternal gingival crevicular fluid at	The investigators will assess changes in local oral inflammation associated with xylitol exposure or not by evaluating the gingival crevicular fluid using a 10-plex pro inflammatory cytokine panel.	Enrolment and at 28-30 weeks, and 4-6 weeks after
Secondary	Alterations within the infants' oral microbiome communities	The investigators will us 16S rRNA sequencing to assess strain level changes within the oral swabs of the infants born during the MAX trial and assess changes in the composition within and between those exposed to xylitol and placebo gum.	4-6 weeks
Secondary	Alterations within the infants' gut microbiome communities	The investigators will use 16S rRNA sequencing to assess strain level changes in the stool/meconium samples from the infants' gut microbiome and assess compositional changes within and between those exposed to xylitol and placebo gum.	4-6 weeks