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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new toothpaste containing tacrolimus, an immunosuppressant drug, to treat individuals with oral chronic graft-versus-host disease (cGVHD). This condition occurs when the immune system attacks the mouth after a transplant. The trial aims to determine if this toothpaste can complement standard treatments and improve oral health. Suitable participants have experienced oral cGVHD and maintained stable immune treatments for at least two weeks. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using tacrolimus on the skin is safe and effective for certain conditions. Specifically, studies with children who have oral chronic graft-versus-host disease (cGVHD) found that a topical form of tacrolimus was safe and effective. This suggests that the new tacrolimus toothpaste might be similarly safe.

Tacrolimus has also been safely used in other forms for conditions like eczema and psoriasis. These findings suggest it could be safe to use in the mouth as a toothpaste. However, since this is an early-stage trial, further research is needed to confirm the safety of the toothpaste specifically. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cGVHD?

Unlike standard treatments for oral graft-versus-host disease, which often involve systemic immunosuppressants or steroids, Tacrolimus Toothpaste offers a new delivery method by applying the medication directly where it's needed—in the mouth. This topical approach helps to minimize systemic side effects since the medication doesn't have to travel through the whole body. Researchers are excited because Tacrolimus is a potent immunosuppressant that can precisely target and potentially reduce inflammation in the mouth, potentially providing relief faster and with fewer side effects than traditional options.

What evidence suggests that tacrolimus toothpaste might be an effective treatment for oral cGVHD?

Research has shown that tacrolimus ointment may help treat severe oral chronic graft-versus-host disease (cGVHD). Some patients experienced significant relief from oral symptoms with this ointment. However, results have varied; one study showed only an 8% improvement in symptoms, while another showed a 50% improvement. Although some trials ended early due to limited results, the treatment still seems promising. In this trial, participants will use tacrolimus as a toothpaste, potentially offering a new way to apply the medication directly to the affected area. While more research is needed, early findings suggest it could help manage oral cGVHD symptoms. ^{5 6 7 8 9}

Who Is on the Research Team?

Allison Bartlett, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

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

I am between 1 and 40 years old.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-1-bronchiolitis-obliterans-syndrome-8-2024-4929e

Tacrolimus Toothpaste for Graft-versus-Host Disease Topical application of 0.1% tacrolimus ointment showed promising results in three patients with severe oral chronic graft-versus-host disease (GvHD), who had ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10198688/

Topical treatment of oral chronic graft-versus-host- disease in ... The OMS response was 8%, and the NIH Oral Cavity Severity Score response 50%. The tacrolimus arm was closed early due to a lack of activity in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724005293

Oral Chronic Graft-versus-Host Disease and Oral Health ... This review provides a practical and concise approach to the diagnosis and management of oral health needs in pediatric and adult alloHCT recipients

4. ashpublications.org ashpublications.org/blood/article/125/4/606/33872/How-we-treat-chronic-graft-versus-host-disease

How we treat chronic graft-versus-host disease | Blood Efficacy cannot yet be assessed because improvement is often not observed until treatment with ECP has been continued for at least 6 months.35,38 ...

5. frontiersin.org frontiersin.org/journals/oral-health/articles/10.3389/froh.2022.903154/full

Oral Chronic Graft-Versus-Host Disease Severe oral chronic graft-versus-host disease following allogeneic bone marrow transplantation: highly effective treatment with topical tacrolimus. Oral Oncol.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8605372/

FK506 (Tacrolimus) monotherapy for prevention of graft- ... This study was designed to obtain first estimates of the safety and efficacy of FK506 monotherapy in the prevention of GVHD following HLA-identical sibling ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497120647607

FK506 (Tacrolimus) Monotherapy for Prevention of Graft- ... We conclude that FK506 monotherapy has an acceptable safety profile and is effective in the prevention of acute GVHD following HLA-identical sibling marrow ...

8. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/478489

Tacrolimus Ointment in the Treatment of Chronic ... Tacrolimus has been shown to be effective topically in atopic dermatitis and systemically in psoriasis and graft-vs-host disease (GVHD). However, its efficacy ...

9. astctjournal.org astctjournal.org/article/S1083-8791(05)00997-3/fulltext

Oral chronic GVHD in children—treatment with topical ... We conclude that topical application of tacrolimus ointment holds promise as a safe and efficacious treatment for oral chronic GVHD in children. These findings ...