Xylitol and the Prevention of Periodontal Disease and Preterm Birth Trial

NCT07424846 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00018356
• Study Type: interventional
• Target: 6,000
• Locations: 1 country
• Sites: 1

Brief Summary

The ground-breaking Prevention of Prematurity and Xylitol (PPaX) cluster randomized controlled clinical trial was conducted in Lilongwe, Malawi and enrolled approximately 10,069 pregnant individuals seeking to evaluate the impact of xylitol-containing chewing gum compared to no chewing gum on reducing the occurrence of maternal periodontal disease, preterm birth, and low birthweight offspring. The premise of this study centers upon the numerous publications supporting a strong association between maternal periodontal disease and preterm birth. Given that xylitol-containing chewing gum is considered a prebiotic and known to reduce cariogenic and periodontopathic bacteria, the study evaluated and discovered a statistically significant reduction in maternal periodontal disease, preterm birth, and low birthweight offspring among pregnant individuals who chewed xylitol-containing chewing gum. While PPaX demonstrated the efficacy of xylitol to reduce preterm birth (PTB), the study had important limitations: (a) PPaX was an unblinded cluster-randomized study with only 8 clusters, 4 with xylitol-containing chewing gum and 4 without any gum (not placebo-controlled); (b) PPaX used a suboptimal dose of 2 grams of xylitol daily which may have reduced the effectiveness of the intervention given that recent literature suggests 5-10 grams/day more effectively improve oral health; and (c) PPaX did not evaluate infant mortality nor early neurodevelopmental outcomes. Notably, reducing fetal exposure to periodontal disease (PD) as well as PTB may improve neurodevelopmental outcomes for offspring as both prematurity and fetal exposure to inflammation are well-documented risk factors for neurodevelopmental delay (NDD) and infant mortality. The investigators will conduct a double-blind, placebo-controlled, individually randomized clinical trial with 3 arms among Malawian pregnant individuals (n=6000) at \<20 weeks of pregnancy with the co-primary outcomes being the incidence of PTB and low birthweight offspring. The 3 study arms (n=2000 each) will be (a) an optimized dose of xylitol-containing chewing gum (6.4 grams/day), (b) the PPaX trial xylitol dose (2.1 grams/day), or (c) flavored sorbitol gum base (placebo control). This trial overcomes the PPaX trial's limitations and will definitively answer whether xylitol prevents PTB in Malawi. The investigators will additionally collect biospecimens from a random sampling of the participants for biobanking for later analysis of inflammatory and microbiome alterations that may occur with xylitol exposure compared with placebo. The investigators hypothesize that pregnant individuals who chew xylitol-containing chewing gum will have a significant reduction in periodontal disease metrics at 28-30 weeks' gestation (e.g. bleeding on probing) as well as offspring with improved neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development 4th edition and reduced risk of adverse pregnancy outcomes including preterm birth.

Conditions

Preterm Birth; Periodontitis; Gingivitis; Developmental Delay; Low Birthweight Neonate

Keywords

xylitol; preterm birth; prematurity; pregnancy; periodontitis; periodontal disease; chewing gum

Outcome Measures

Primary Outcomes (2)

• Preterm Birth

  \<37 weeks gestation

  delivery

• Low birthweight offspring

  \<2500 gram birthweight of offspring

  at delivery

Secondary Outcomes (5)

• Neonatal mortality

  first 28 days after delivery

• Infant Mortality

  1 year after birth

• Neurodevelopmental Outcomes at 12 months

  1 year after birth

• Periodontitis

  at 28-30 weeks of pregnancy at 6-8 weeks postpartum (in the enrolled pregnant individuals)

• Gingivitis

  at 28-30 weeks of pregnancy at 6-8 weeks postpartum (in the enrolled pregnant individuals)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Sorbitol flavored chewing gum (0 grams of xylitol/day)

Other: Sorbitol chewing gum

2 grams xylitol/day

EXPERIMENTAL

Xylitol flavored chewing gum (2 grams of xylitol/day). The participants will receive 4 pellets of sorbitol (placebo) gum per day as well as 2 pellets of xylitol (intervention) gum per day in pre-packaged blister packs to ensure double-blinded study design.

Drug: Xylitol Chewing gum; Other: Sorbitol chewing gum

6 grams xylitol/day

EXPERIMENTAL

Xylitol flavored chewing gum (6 grams of xylitol/day)

Drug: Xylitol Chewing gum

Interventions

Xylitol Chewing gum DRUG

Xylitol chewing gum (1 gram per pellet of gum). This is a dietary supplement, but clinicaltrials.gov requires us to identify it as a "drug" due to IND requirements.

2 grams xylitol/day; 6 grams xylitol/day

Sorbitol chewing gum OTHER

Sorbitol (non-xylitol) chewing gum. This is a dietary supplement, but clinicaltrials.gov requires us to identify it as a "drug" due to IND requirements.

2 grams xylitol/day; Placebo

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent. For those under 18 years of age, an approval will additionally be sought from the parent or guardian
• Less than 20 weeks' gestation (by best obstetric estimate)
• At least 20 natural teeth
• Planning to deliver at one of the health facilities within the XaPPP trial
• Receiving antenatal obstetric care at one of the 8 health districts
• Willing to chew two pieces of gum thrice daily for 5 minutes after the morning, day and evening meals throughout pregnancy
• Willing to attend all study visits
• Willing to provide biospecimens (oral, vaginal, placental, breast milk)
• Willing to undergo at least two dental exams including oral microbiota sampling at study enrolment \<20 weeks of pregnancy, 28-30 weeks of pregnancy, and 6-8 weeks after giving birth
• Willing to have their child undergo follow up through at least 12 months after birth including neurodevelopmental examination(s)
• Speaks Chichewa or English

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)
• Known allergy to xylitol

Sponsors & Collaborators

• University of Washington: lead
• Baylor College of Medicine: collaborator
• Baylor College of Medicine Children's Foundation: collaborator

Study Sites (1)

Baylor College of Medicine Children's Foundation Malawi

Lilongwe, Malawi

RECRUITING

MeSH Terms

Conditions

Premature Birth; Periodontitis; Gingivitis; Learning Disabilities; Periodontal Diseases

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Mouth Diseases; Stomatognathic Diseases; Infections; Gingival Diseases; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Greg Valentine

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Greg Valentine, MD MED FAAP

CONTACT

2066167378; gcvalent@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor: Pediatrics

Model Details: Three-arm, Double-blind, placebo-controlled, individually randomized clinical trial

Study Record Dates

• First Submitted: February 14, 2026
• First Posted: February 20, 2026
• Study Start: March 26, 2026
• Primary Completion (Estimated): September 30, 2030
• Study Completion (Estimated): September 30, 2030
• Last Updated: June 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: The information will be available 1 year after the completion of the last participant's data is entered and the database is finalized.
• Access Criteria: cientific data will be findable and identifiable via DASH or through directly contacting the PI (Valentine) or associated XaPPP trial investigators. If other NIH-sponsored data archives are available and preferred by Access will be limited to registered users who submit proposed specific questions or analysis plans and sign a data use agreement. "Supervised" indicates that individual requests are reviewed to protect the intellectual property rights of the project investigative team by restricting external development of manuscripts using the study data that substantially overlap with those that are already in development by study investigators. We will form a publications committee, with investigator representatives from the Study Team at the University of Washington (Seattle, Washington, USA), Baylor College of Medicine Children's Foundation-Malawi (Lilongwe, Malawi), and Baylor College of Medicine (Houston, Texas, USA) to establish manuscript development and publication guidelines.

Locations

MA (1)