Microbiome Alterations With Xylitol (MAX) in Pregnancy

Not Applicable

Recruiting

• Conditions: Dysbiosis; Inflammation Gum
• Interventions: Dietary Supplement: Sorbitol gum; Dietary Supplement: Xylitol gum

• Registration Number: NCT06329596
• Lead Sponsor: Baylor College of Medicine

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

Detailed 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.

Study Timeline

• Study First Submitted: 2024-03-18
• Study First Submitted QC: 2024-03-25
• Study First Posted: 2024-03-26
• Status Verified: 2024-06
• Study Start: 2024-06-13
• Last Update Submitted: 2024-06-27
• Last Update Posted: 2024-06-28
• Primary Completion: 2025-03-31
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 50

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Periodontal disease at 28-30 weeks of pregnancy	Enrolment and 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.

Secondary Outcome Measures

Name	Time	Method
Alterations within the infants' oral microbiome communities	4-6 weeks	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.
Alterations within the infants' gut microbiome communities	4-6 weeks	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.
Periodontal disease at 6 weeks postpartum	Enrolment and 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.
Alterations in the maternal oral microbiome communities delivery	Enrolment and at 28-30 weeks, delivery and 4-6 weeks after	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.
Alterations in the maternal vaginal microbiome communities	Enrolment and at 28-30 weeks, delivery and 4-6 weeks after	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
Inflammatory mediator changes in the maternal gingival crevicular fluid at	Enrolment and at 28-30 weeks, and 4-6 weeks after	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.

Trial Locations

Locations (1)

Area 25 Health Center; 🇲🇼 Lilongwe, Malawi