Xylitol Wipes for Bloodstream Infections in Stem Cell Transplant Patients

Recruiting at 2 trial locations

Overseen By Kelly McIntosh

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Recent oral radiation, Xylitol allergy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 33 days

419 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, you must avoid chewing gum and toothpaste that contain xylitol during the study.

What data supports the effectiveness of the treatment Xylitol Wipes for Bloodstream Infections in Stem Cell Transplant Patients?

Research shows that using xylitol wipes can improve oral health and reduce bloodstream infections from oral bacteria in stem cell transplant patients. In a study, patients using xylitol wipes had fewer infections and harmful bacteria compared to those who did not use the wipes. ^{1 2 3 4 5}

Is xylitol safe for use in humans?

Xylitol is generally considered safe for human use, as studies have shown no significant harmful effects in both humans and animals. However, consuming large amounts of xylitol can cause diarrhea. ^{1 4 5 6 7}

How is the treatment with xylitol wipes different from other treatments for bloodstream infections in stem cell transplant patients?

Xylitol wipes are unique because they target oral bacteria that can lead to bloodstream infections, improving oral health and reducing infection risk in stem cell transplant patients, unlike standard treatments that do not specifically address oral sources of infection. ^{2 4 5 8 9}

Research Team

Christopher Dandoy, MD, MSc

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for children and young adults aged 4 months to 25 years who are undergoing stem cell transplantation. Participants must have at least one tooth, not use xylitol-containing products during the study, and be treated at specific hospitals. Those with allergies to grapes or xylitol, recent radiation treatment in the head or neck area, or those having a transplant without prior chemotherapy/radiation are excluded.

Inclusion Criteria

Provide signed and dated informed consent and assent (when applicable) form

I am scheduled for a stem cell transplant at a specified hospital.

I agree not to use xylitol-containing gum or toothpaste during the study.

Exclusion Criteria

Known history of allergy to grapes or grape flavoring

I had radiation for cancer in my mouth, head, or neck within the last 6 months.

Known history of allergy to xylitol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive twice-daily intraoral xylitol-wipe or placebo application

33 days

Daily application

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Xylitol

Trial Overview The trial tests if using xylitol wipes in the mouth twice daily can prevent bloodstream infections from oral bacteria in pediatric patients receiving stem cell transplants. It's a randomized study where some will get xylitol wipes and others a placebo, without knowing which they received.

Participant Groups

Group I: Xylitol Experimental Treatment 1 Intervention

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.

Group II: Grape-flavored Wipes Placebo Group 1 Intervention

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.

Xylitol is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Xylitol for:

• Prevention of tooth decay
• Sugar substitute

Approved in European Union as Xylitol for:

• Prevention of tooth decay
• Sugar substitute

Approved in Canada as Xylitol for:

• Prevention of tooth decay
• Sugar substitute

Approved in Japan as Xylitol for:

• Prevention of tooth decay
• Sugar substitute

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

National Institute of Dental and Craniofacial Research (NIDCR)

Collaborator

Trials

312

Recruited

853,000+

Findings from Research

The combination of xylitol, sodium fluoride (NaF), and zinc chloride (ZnCl2) effectively inhibited the growth of the bacteria S. Sobrinus OMZ 176 in a laboratory setting, suggesting a potential strategy for dental health.

The mechanism of action involves reduced glucose uptake and inhibition of glycolysis at key metabolic points, along with increased accumulation of xylitol metabolites, which together contribute to the suppression of bacterial growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined effect of xylitol, NaF and ZnCl2 on growth and metabolism of Streptococcus sobrinus OMZ 176. Scheie, AA., Assev, S., Rölla, G.[2019]

In a blinded randomized crossover trial involving healthy adolescents, xylitol tablets without red propolis (XT) were found to be effective in controlling harmful bacteria like Streptococcus spp. in dental biofilms, suggesting their potential for improving oral health.

Both xylitol tablets with (XPT) and without (XT) red propolis showed similar acceptability among participants, but XT had a higher purchase intention, indicating a preference for the simpler formulation despite propolis not enhancing the benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of xylitol tablets with and without red propolis on salivary parameters, dental biofilm and sensory acceptability of adolescents: a randomized crossover clinical trial. Martins, ML., Monteiro, ASN., Vieira, TI., et al.[2021]

Xylitol demonstrates significant antimicrobial effects against Candida albicans, with a minimum inhibitory concentration (MIC) of 20 × 10^4 μg/mL and a minimum fungicidal concentration (MFC) of 40 × 10^4 μg/mL, indicating its potential to inhibit and kill the fungus.

The findings suggest that xylitol could be effectively incorporated into dental products like gums, toothpastes, and mouthwashes to help treat or prevent candidiasis, especially in individuals with compromised immune systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antifungal Activity of Xylitol against Candida albicans: An in vitro Study. Talattof, Z., Azad, A., Zahed, M., et al.[2019]

A study of 41 pediatric patients undergoing hematopoietic cell transplantation found a significant association between high dental caries risk and increased likelihood of bloodstream infections (BSI), with high-risk children being 21 times more likely to develop BSI.

The oral microbiome of children with high caries risk showed reduced microbial diversity and was enriched in cariogenic bacteria, suggesting that the presence of these bacteria may contribute to the risk of BSI in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dental caries as a risk factor for bacterial blood stream infection (BSI) in children undergoing hematopoietic cell transplantation (HCT). Abduweli Uyghurturk, D., Lu, Y., Urata, J., et al.[2023]

In a study involving pediatric hematopoietic stem cell transplantation (HSCT) recipients, daily xylitol wipes significantly improved oral health, reducing gingivitis, oral plaque, and ulcers compared to standard oral care.

The xylitol group experienced no bloodstream infections (BSIs) from oral organisms, while the standard care group had four cases, indicating that xylitol not only enhances oral hygiene but also effectively decreases the risk of serious infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving Oral Health and Modulating the Oral Microbiome to Reduce Bloodstream Infections from Oral Organisms in Pediatric and Young Adult Hematopoietic Stem Cell Transplantation Recipients: A Randomized Controlled Trial. Badia, P., Andersen, H., Haslam, D., et al.[2021]

Xylitol is a non-cariogenic sugar substitute that not only helps prevent cavities but also has a bacteriostatic effect against harmful bacteria like Strep mutans and Strep sanguis, which can take it up but cannot metabolize it.

The combination of xylitol and sorbitol enhances the anti-caries effect, as xylitol inhibits the metabolism of sorbitol by Strep mutans, making this combination both effective and cost-efficient, although high doses of xylitol can cause diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Xylitol, mechanisms of action and uses]. Wåler, SM., Rølla, G.[2013]

Xylitol crystals produced from corncob using the yeast Pichia caribbica are highly pure (>98%) and show no harmful contaminants that could affect mammalian cell growth.

In toxicity trials with female Wistar rats, xylitol demonstrated a high safety profile with an LD50 greater than 10,000 mg/kg, indicating it is safe for use as a food-grade ingredient pending further human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food-grade xylitol production from corncob biomass with acute oral toxicity studies. Dasgupta, D., Ahuja, V., Singh, R., et al.[2023]

In a study of 10 patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT), oral management, including dental treatments and hygiene instructions, was implemented to prevent bloodstream infections from oral bacteria, and no bacterial species were found in the blood during the observation period.

Despite all patients experiencing oral mucositis and periodontitis, the study provides microbiological evidence that effective oral management can help prevent bloodstream infections in ASCT recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of oral management in allogeneic hematopoietic stem cell transplantation recipients: microbiological evidence based on molecular analysis of oral bacteria. Kawajiri, J., Nagata, K., Nakamura, A., et al.[2021]

Xylitol effectively inhibits the growth of Streptococcus mutans in a dose-dependent manner, suggesting it could be useful in preventing dental caries caused by this bacteria.

The proposed mechanism for xylitol's effectiveness may involve its impact on glucose transport across the bacterial cell membrane, while sorbitol did not inhibit growth but only delayed bacterial growth phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth inhibition of Streptococcus mutans strain OMZ 176 by xylitol. Assev, S., Vegarud, G., Rölla, G.[2019]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

Combined effect of xylitol, NaF and ZnCl2 on growth and metabolism of Streptococcus sobrinus OMZ 176. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Effect of xylitol tablets with and without red propolis on salivary parameters, dental biofilm and sensory acceptability of adolescents: a randomized crossover clinical trial. [2021]

3. India pubmed.ncbi.nlm.nih.gov

Antifungal Activity of Xylitol against Candida albicans: An in vitro Study. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Dental caries as a risk factor for bacterial blood stream infection (BSI) in children undergoing hematopoietic cell transplantation (HCT). [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Improving Oral Health and Modulating the Oral Microbiome to Reduce Bloodstream Infections from Oral Organisms in Pediatric and Young Adult Hematopoietic Stem Cell Transplantation Recipients: A Randomized Controlled Trial. [2021]

6. Norway pubmed.ncbi.nlm.nih.gov

[Xylitol, mechanisms of action and uses]. [2013]

7. Germany pubmed.ncbi.nlm.nih.gov

Food-grade xylitol production from corncob biomass with acute oral toxicity studies. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Clinical utility of oral management in allogeneic hematopoietic stem cell transplantation recipients: microbiological evidence based on molecular analysis of oral bacteria. [2021]

9. Denmark pubmed.ncbi.nlm.nih.gov

Growth inhibition of Streptococcus mutans strain OMZ 176 by xylitol. [2019]