Xylitol BSI Multisite - Reduction of Bloodstream Infections From Oral Organisms in Pediatric Stem Cell Transplant

Reduction of Bloodstream Infections From Oral Organisms in Pediatric Stem Cell Transplant: a Randomized, Multicenter, Double-blind , Placebo-controlled Study Evaluating Twice Daily Oral Xylitol

Bloodstream infections (BSI) caused by bacteria translocating across injured oral mucosa are a significant cause of morbidity and mortality in patients undergoing stem cell transplantation (SCT). Unfortunately, there are currently no known strategies to prevent these BSI in this vulnerable population. The investigators will conduct a randomized, double-blind, placebo-controlled trial at three institutions to evaluate the effectiveness of twice daily intraoral xylitol-wipe application on reducing BSI in pediatric SCT patients.

Study Overview

• Status: Recruiting
• Conditions: Allogeneic Stem Cell Transplantation
• Intervention / Treatment: Other: Xylitol; Other: Placebo

Detailed Description

Patients will be randomized to receive either twice-daily intraoral grape-flavored xylitol-wipe (intervention arm) or grape-flavored saline wipe (control arm) application in addition to the current standard of care (SOC). The purpose of this study is to determine whether xylitol wipes are effective at reducing bloodstream infections (BSIs), dental plaque, mucositis (redness and ulcers in the mouth), or gingivitis in patients who undergo hematopoietic stem cell transplant.

• Study Type: Interventional
• Enrollment (Estimated): 419
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kelly McIntosh; Phone Number: 513-803-0460; Email: Kelly.McIntosh@cchmc.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Contact: Vanessa Fabrizio; Phone Number: 720-777-1982; Email: vanessa.fabrizio@cuanschutz.edu
      • Principal Investigator: Vanessa Fabrizio, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana-Farber/Boston Children's
      • Principal Investigator: Leslie Lehmann, MD
      • Contact: Leslie Lehmann, MD; Phone Number: 617-632-3352; Email: leslie_lehmann@dfci.harvard.edu
      • Contact: Paola Tabares; Email: paola_tabares@dfci.harvard.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Principal Investigator: Christopher Dandoy, MD, MSc
      • Contact: Kelly McIntosh; Phone Number: 513-803-0460; Email: Kelly.McIntosh@cchmc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provide signed and dated informed consent and assent (when applicable) form
• Willing to comply with all study procedures and be available for the duration of the study
• Admitted and planning to undergo an allogeneic stem cell transplant (SCT) at Cincinnati Children's Hospital Medical Center (CCHMC), Boston Children's Hospital, or Children's Hospital of Colorado (Denver).
• Male or female, 4 months to 25 years of age at the time of SCT (Day 0)
• Have a minimum of one tooth
• Agree to avoid chewing gum and toothpaste that contains xylitol during the intervention period

Exclusion Criteria:

• Prior radiation treatment for cancer of the oral cavity, head, or neck in the past 6 months per the study participant's medical record
• Cranial boost in patients receiving total body irradiation
• Known history of allergy to xylitol
• Known history of allergy to grapes or grape flavoring
• Undergoing a conditioning-free allogeneic stem cell transplant (patient does not receive any chemotherapy or radiation prior to stem cell infusion)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xylitol; Xylitol, a naturally occurring sugar alcohol found in plums, strawberries, and various vegetables such as cauliflower, has been approved for use in food by the US FDA since 1963. Spiffies Xylitol Wipes will be used.	Other: Xylitol; Xylitol wipes; Other Names: Spiffies Xylitol Wipes
Placebo Comparator: Grape-flavored Wipes; Grape-flavored wipes will be used with 2 drops of PCCA colorless grape flavoring. The grape-flavored wipes each contain a solution of 0.9% Sodium Chloride, purified water, and Benzalkonium chloride. PCCA artificial colorless grape flavoring will be used. The PCCA grape flavoring contains propylene glycol, ethyl alcohol, and artificial flavoring.	Other: Placebo; Placebo wipes; Other Names: Grape-Flavored Wipes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacteremia from an oral organism	Incidence of bloodstream infection (BSI) from oral flora organisms in in patients receiving xylitol compared to placebo	33 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacteremia from other non-oral flora organisms	Incidence of BSI from non-oral flora organisms in patients receiving xylitol compared to placebo	33 days
Dental plaque	Debris Index Simplified (DI-S) score	33 days
Gingivitis	Mean Modified Gingival Index (MGI) score	33 days
Objective mucositis	Mean Oral Mucositis Assessment Scale (OMAS) score	33 days
Patient-reported mucositis	ChIMES total score	33 days
Oral microbiome diversity	Shannon Diversity Index	33 days

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: National Institute of Dental and Craniofacial Research (NIDCR)
• Investigators: Principal Investigator: Christopher Dandoy, MD, MSc, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: mucositis; bloodstream infections; oral health; xylitol; dental health; gingivitis; plaque
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Infections
• Other Study ID Numbers: 2021-0537; 1UG3DE030401-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No