Xylitol and the Prevention of Periodontal Disease and Preterm Birth Trial

Официальное название

Xylitol and the Prevention of Periodontal Disease and Preterm Birth (XaPPP) Trial

Обзор

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.

Вмешательства

• Препарат Xylitol Chewing gum
  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.
• Другое Sorbitol chewing gum
  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.

Первичные конечные точки

• Preterm Birth [Срок оценки: delivery]
• Low birthweight offspring [Срок оценки: at delivery]

Вторичные конечные точки (5)

• Neonatal mortality [Срок оценки: first 28 days after delivery]
• Infant Mortality [Срок оценки: 1 year after birth]
• Neurodevelopmental Outcomes at 12 months [Срок оценки: 1 year after birth]
• Periodontitis [Срок оценки: at 28-30 weeks of pregnancy at 6-8 weeks postpartum (in the enrolled pregnant individuals)]
• Gingivitis [Срок оценки: at 28-30 weeks of pregnancy at 6-8 weeks postpartum (in the enrolled pregnant individuals)]

Критерии участия

Критерии включения

• 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

All patients who meet inclusion criteria will be approached without regard to sex, race, ethnicity, parents' country of origin, or religious preferences.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

Malawi · 1 центр

• Baylor College of Medicine Children's Foundation Malawi — Lilongwe

Идентификаторы

NCT: NCT07424846 · STUDY00018356

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗