Tacrolimus Toothpaste for Graft-versus-Host Disease

Overseen By Allison Bartlett, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Herpes simplex virus, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

13 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications. However, it requires that your immune suppression treatment is stable for at least two weeks before joining.

What data supports the effectiveness of the drug Tacrolimus Toothpaste for treating graft-versus-host disease?

Research shows that tacrolimus ointment, a similar form of the drug, has been highly effective in treating oral graft-versus-host disease, providing rapid and significant improvement in patients who had not responded to other treatments. ^{1 2 3 4 5}

How is Tacrolimus Toothpaste different from other treatments for graft-versus-host disease?

Tacrolimus Toothpaste is unique because it delivers the drug directly to the oral tissues, potentially reducing systemic side effects compared to traditional oral or intravenous administration. This localized approach may offer a novel way to manage oral symptoms of graft-versus-host disease, which is not typically addressed by standard treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

This study aims to investigate the use of a novel formulation of tacrolimus, as a toothpaste, in a population of patients with oral chronic graft vs. host disease (cGVHD) as an adjunctive therapy in addition to standard-of-care systemic therapy. The investigators plan to summarize our findings to add to the current body of literature regarding managing cGVHD, specifically those with oral involvement. Additionally, establishing effective topical application of tacrolimus in the oral cavity will allow for future prospective studies comparing outcomes for these patients with a more traditional standard of care.

Research Team

Allison Bartlett, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for patients with oral chronic graft vs. host disease (cGVHD), specifically those who have complications like Bronchiolitis Obliterans Syndrome, Graft-versus-Host Disease, or Oral mucositis. Participants should be currently receiving standard systemic therapy for cGVHD.

Inclusion Criteria

My immune suppression has been stable for the last two weeks.

I am between 1 and 40 years old.

I have chronic graft-versus-host disease affecting my mouth.

Exclusion Criteria

I have or might have a cold sore outbreak in my mouth.

I recently had a change in my immune suppression treatment for chronic graft vs. host disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tacrolimus toothpaste as an adjunctive therapy for oral chronic graft vs. host disease

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tacrolimus Toothpaste

Trial Overview The study is testing tacrolimus toothpaste as an additional treatment for oral cGVHD. The goal is to see if applying tacrolimus directly in the mouth helps manage symptoms better than the usual care alone.

Participant Groups

Group I: Topical Tacrolimus Treatment Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Findings from Research

An adolescent with acute oral graft-versus-host disease (GvHD) was successfully treated with tacrolimus 0.1% ointment, suggesting its potential effectiveness for this condition.

Although tacrolimus ointment is not officially approved for treating oral GvHD, this case provides preliminary evidence that it may be a viable option when standard treatments fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly effective treatment with tacrolimus ointment in an adolescent with oral graft-versus-host disease. Bauters, T., Bordon, V., Van de Velde, V., et al.[2021]

Topical application of 0.1% tacrolimus ointment showed promising results in three patients with severe oral chronic graft-versus-host disease (GvHD), who had not responded to previous treatments.

Patients experienced rapid and significant improvements in symptoms, indicating that tacrolimus may be an effective alternative treatment for managing oral GvHD complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe oral chronic graft-versus-host disease following allogeneic bone marrow transplantation: highly effective treatment with topical tacrolimus. Eckardt, A., Starke, O., Stadler, M., et al.[2013]

Extended-release tacrolimus (tacrolimus ER) is as effective as the traditional twice-daily formulation in preventing transplant rejection in adult kidney transplant recipients, based on phase III/IV trials with follow-up up to 4 years.

Tacrolimus ER shows better renal function compared to ciclosporin and has a similar tolerability profile to the original formulation, making it a convenient once-daily option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release tacrolimus: a review of its use in de novo kidney transplantation. McCormack, PL.[2022]

Switching from the twice-daily tacrolimus (Prograf) to the once-daily extended-release formulation (Advagraf) in 49 kidney transplant patients led to an increased openness about their transplant experience after 6 months, indicating a potential improvement in quality of life.

However, 8 out of the 49 patients had to switch back to the original formulation due to adverse events, suggesting that while the switch may have benefits, it also carries risks that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of switching from twice-daily to once-daily tacrolimus formulation on quality of life, anxiety, and transplant benefit perception after kidney transplantation. Calia, R., Lai, C., Aceto, P., et al.[2015]

The extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) shows similar efficacy to the immediate-release version (Prograf®) in kidney transplant recipients, with no significant differences in patient/graft survival, acute rejection rates, or renal function across studies involving over 2,500 patients.

Advagraf® significantly improves medication adherence compared to Prograf®, which is crucial for long-term transplant success, and it has also been associated with favorable outcomes when combined with mTOR inhibitors, potentially reducing the risk of late-onset cytomegalovirus infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advagraf® with or without an induction therapy for de novo kidney-transplant recipients. Noble, J., Jouve, T., Rostaing, L., et al.[2021]

Fluoride-free toothpastes containing biomimetic calcium-phosphate-based ingredients, particularly hydroxyapatite (HAP), have been shown in clinical trials to effectively improve various aspects of oral health, including caries prevention and reducing dentin hypersensitivity.

Among the different calcium phosphate formulations studied, HAP was the most extensively tested and demonstrated the greatest versatility in enhancing oral health outcomes, making it a promising alternative to fluoride-containing products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving Oral Health with Fluoride-Free Calcium-Phosphate-Based Biomimetic Toothpastes: An Update of the Clinical Evidence. Limeback, H., Enax, J., Meyer, F.[2023]

Clinpro White Varnish demonstrated the best biocompatibility with human gingival fibroblast cells, maintaining cell viability and normal morphology even at higher concentrations, making it a strong candidate for topical applications.

In contrast, Embrace Varnish showed significant cytotoxicity, leading to lower cell viability and abnormal cell morphology, which could hinder healing and regeneration of oral tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Biocompatibility of CPP-ACP and Fluoride-containing Desensitizers on Human Gingival Cells. López-García, S., Guerrero-Gironés, J., Pecci-Lloret, MP., et al.[2022]

All four calcium compound-based root canal sealers tested were found to be non-cytotoxic, indicating they are safe for use in dental procedures.

ARS, MTA Fillapex, and iRoot SP not only reduced inflammation more effectively than Sealapex but also promoted better bone-forming cell activity, suggesting they are superior options for enhancing healing in periodontal ligament cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro biocompatibility, inflammatory response, and osteogenic potential of 4 root canal sealers: Sealapex, Sankin apatite root sealer, MTA Fillapex, and iRoot SP root canal sealer. Chang, SW., Lee, SY., Kang, SK., et al.[2022]

The novel sol-gel bioactive glass effectively reduces dentinal fluid flow, which is a key factor in dentinal hypersensitivity, as demonstrated through experiments measuring fluid flow after treatment on cut tooth surfaces.

The bioactive glass showed sustained effectiveness in occluding dental tubules even after exposure to brushing and acidic solutions, indicating its potential for long-lasting relief from dentinal hypersensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomimetic dentin desensitizer based on nano-structured bioactive glass. Mitchell, JC., Musanje, L., Ferracane, JL.[2013]

A study involving 134 participants found that all tested dentifrices, including those with smaller particle size CSPS and different fluoride sources, significantly improved dentin hypersensitivity (DH) after 2, 4, and 8 weeks of use.

However, there was no clear advantage of the CSPS-containing dentifrices over a regular fluoride dentifrice, suggesting that the expected benefits of CSPS may not have been realized in this study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Clinical Trial Investigating the Effect of Particle Size of Calcium Sodium Phosphosilicate (CSPS) on the Efficacy of CSPS-containing Dentifrices for the Relief of Dentin Hypersensitivity. Zang, P., Parkinson, C., Hall, C., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Highly effective treatment with tacrolimus ointment in an adolescent with oral graft-versus-host disease. [2021]

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

Severe oral chronic graft-versus-host disease following allogeneic bone marrow transplantation: highly effective treatment with topical tacrolimus. [2013]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Extended-release tacrolimus: a review of its use in de novo kidney transplantation. [2022]

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

Effects of switching from twice-daily to once-daily tacrolimus formulation on quality of life, anxiety, and transplant benefit perception after kidney transplantation. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Advagraf® with or without an induction therapy for de novo kidney-transplant recipients. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Improving Oral Health with Fluoride-Free Calcium-Phosphate-Based Biomimetic Toothpastes: An Update of the Clinical Evidence. [2023]

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

In Vitro Biocompatibility of CPP-ACP and Fluoride-containing Desensitizers on Human Gingival Cells. [2022]

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

In vitro biocompatibility, inflammatory response, and osteogenic potential of 4 root canal sealers: Sealapex, Sankin apatite root sealer, MTA Fillapex, and iRoot SP root canal sealer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Biomimetic dentin desensitizer based on nano-structured bioactive glass. [2013]

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

A Randomized Clinical Trial Investigating the Effect of Particle Size of Calcium Sodium Phosphosilicate (CSPS) on the Efficacy of CSPS-containing Dentifrices for the Relief of Dentin Hypersensitivity. [2018]