Xylitol and the Prevention of Periodontal Disease and Preterm Birth Trial

Sponsor
University of Washington
Study ID
NCT07424846
Phase
PHASE2/PHASE3
Status
Recruiting
Apply to this trial

Conditions

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

Eligibility Criteria

Sex
FEMALE
Age
N/A - N/A
Healthy Volunteers
Not accepted

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.
  • 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.

Study Details

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.

Key Dates

First listed
Feb 20, 2026
Start date
Mar 26, 2026
Status verified
Jun 2026
Primary completion
Sep 30, 2030
Completion
Sep 30, 2030

Study Design

Enrollment
6,000 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION

Arms

  • Placebo Comparator: Placebo
    Sorbitol flavored chewing gum (0 grams of xylitol/day)
  • Experimental: 2 grams xylitol/day
    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.
  • Experimental: 6 grams xylitol/day
    Xylitol flavored chewing gum (6 grams of xylitol/day)

Primary Outcome Measure

Preterm Birth [ Time Frame: delivery ]

Central Contacts

Related Studies