Tacrolimus Toothpaste for Graft-versus-Host Disease
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Children's Hospital Medical Center, Cincinnati
Disqualifiers: Herpes simplex virus, others
Stay on Your Current Meds
No Placebo Group
Approved in 4 Jurisdictions
Trial Summary
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.
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.
12345How 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.
678910Eligibility 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.
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Topical Tacrolimus TreatmentExperimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cincinnati Children's Hospital Medical CenterCincinnati, OH
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Who Is Running the Clinical Trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
References
Highly effective treatment with tacrolimus ointment in an adolescent with oral graft-versus-host disease. [2021]We report a case of acute oral graft-versus-host disease in an adolescent, which was successfully treated with tacrolimus 0.1% ointment.
Severe oral chronic graft-versus-host disease following allogeneic bone marrow transplantation: highly effective treatment with topical tacrolimus. [2013]Oral involvement of chronic graft-versus-host disease (GvHD) is a most distressing and disabling complication of hematopoietic cell transplantation, for which systemic immunosuppression as well as topical corticosteroid treatment may offer only limited symptomatic relief. Here we report encouraging preliminary results with the application of tacrolimus (FK-506) as a 0.1% ointment in three patients with severe oral chronic GvHD, heavily pretreated without success, who experienced rapid, consistent, complete or at least marked, subjective and objective improvement with topical tacrolimus.
Extended-release tacrolimus: a review of its use in de novo kidney transplantation. [2022]Extended-release tacrolimus (tacrolimus ER) [Advagraf(®); Astagraf XL(®); Graceptor(®); Prograf XL(®)] is a once-daily formulation of the immunosuppressive calcineurin inhibitor, which is approved in many countries worldwide for the prophylaxis of transplant rejection in adult de novo kidney transplant recipients. It is absorbed more slowly than the conventional, twice-daily, immediate-release formulation, initially producing lower exposure when administered at the same daily dosage, but providing equivalent exposure upon repeat administration with therapeutic drug monitoring. In randomized, controlled, phase III/IV trials, with extended follow-up to 4 years, the efficacy of tacrolimus ER was similar to that of twice-daily tacrolimus with regard to the prevention of acute rejection or graft dysfunction in adult de novo kidney transplant recipients. Renal function was significantly better with tacrolimus ER, but not tacrolimus, than with ciclosporin. The tolerability profile of tacrolimus ER was descriptively similar to that of the original twice-daily formulation, with no notable differences. Therefore, tacrolimus ER retains the immunosuppressive activity of the original formulation in the prophylaxis of transplant rejection in adult de novo kidney transplant recipients and offers the benefits of once-daily administration.
Effects of switching from twice-daily to once-daily tacrolimus formulation on quality of life, anxiety, and transplant benefit perception after kidney transplantation. [2015]This study investigated whether switching from the twice-daily (Prograf; TAC) to the once-daily formulation of tacrolimus with extended release (Advagraf; XL) affected quality of life, anxiety, and transplant benefit perception after allogeneic kidney transplantation.
Advagraf® with or without an induction therapy for de novo kidney-transplant recipients. [2021]Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company). Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i.e., basiliximab) in de novo kidney-transplant recipients. To achieve this, we searched for suitable articles through PubMed. Expert commentary: Phases-III and -IV studies comparing Advagraf®/Astagraf XL® to Prograf® in association with mycophenolate mofetil (more than 2,500 patients) have demonstrated overall similar results with regards to patient/graft survival, biopsy-proven acute-rejection rate, and renal function (p > 0.05). A randomized controlled study in maintenance kidney transplant patients has shown (using electronic monitoring) that, as compared to Prograf®, Advagraf® significantly improved adherence to medication. Other studies report that Advagraf®-treated patients receiving a mTOR-inhibitor agent (sirolimus or everolimus) instead of MMF: this was associated with good allograft outcome, and might also prevent late-onset cytomegalovirus infection. Advagraf®-based immunosuppression given to de novo kidney-transplant recipients, with or without an induction therapy, provided excellent results compared to Prograf®; it also increased patients' adherence to treatment.
Improving Oral Health with Fluoride-Free Calcium-Phosphate-Based Biomimetic Toothpastes: An Update of the Clinical Evidence. [2023]As the demand for clinically effective fluoride-free oral care products for consumers increases, it is important to document which types of toothpastes have been shown in clinical studies to be effective in improving oral health. In this review, we included different indications, i.e., caries prevention, improving periodontal health, reducing dentin hypersensitivity, protecting against dental erosion, and safely improving tooth whitening in defining what constitutes improvement in oral health. While there are several professional and consumer fluoride-containing formulations fortified with calcium-phosphate-based ingredients, this review focuses on fluoride-free toothpastes containing biomimetic calcium-phosphate-based molecules as the primary active ingredients. Several databases were searched, and only clinical trials in human subjects were included; in vitro and animal studies were excluded. There were 62 oral health clinical trials on biomimetic hydroxyapatite (HAP), 57 on casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), 26 on calcium sodium phosphosilicate (CSPS, or so called Bioglass), and 2 on β-tricalcium phosphate (β-TCP). HAP formulations were tested the most in clinical trials for benefits in preventing caries, dentin hypersensitivity, improving periodontal health, and tooth whitening. Based on the current clinical evidence to date, fluoride-free HAP toothpaste formulations are the most versatile of the calcium phosphate active ingredients in toothpastes for improving oral health.
In Vitro Biocompatibility of CPP-ACP and Fluoride-containing Desensitizers on Human Gingival Cells. [2022]To analyze the biocompatibility of different desensitizers containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and fluoride in their composition: MI Varnish (MV), Clinpro White Varnish (3M Oral Care), Profluorid Varnish (VOCO), Duraphat (Colgate) and Embrace Varnish (Pulpdent) on human gingival fibroblast cells (hGF).
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]The objective of this study was to compare the cytotoxicity, inflammatory response, osteogenic effect, and the signaling mechanism of these biologic activities of 4 calcium compound-based root canal sealers (ie, Sealapex [Sybron Kerr, WA], apatite root sealer [ARS; Dentsply Sankin, Tokyo, Japan], MTA Fillapex [Angelus Indústria de Produtos Odontológicos S/A, Londrina, PR, Brazil], and iRoot SP [Innovative BioCreamix Inc, Vancouver, Canada]) in human periodontal ligament cells.
Biomimetic dentin desensitizer based on nano-structured bioactive glass. [2013]This study evaluated the ability of a novel sol-gel bioactive glass, in conjunction with appropriate carrier vehicles, to reduce dentinal fluid flow, with an eye toward reducing dentinal hypersensitivity.
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]To investigate the effect of reducing the particle size of calcium sodium phosphosilicate (CSPS) bioactive glass from ~14 µm (NovaMin®) to ~4 µm (Vitryxx®), and of changing the fluoride source in a 5% CSPS dentifrice from sodium monofluorophosphate (SMFP) to sodium fluoride (NaF) on the efficacy of CSPS-containing dentifrices in dentin hypersensitivity (DH) relief.