Dexamethasone to Prevent Oral Chronic Graft-versus-Host Disease
This study will determine if a dexamethasone mouth rinse can reduce the risk of developing oral chronic graft-versus-host disease (cGVHD) in patients who have undergone a bone marrow (stem cell) transplant procedure. cGVHD is a common complication of stem cell transplantation, resulting from the donor cells attacking the transplant recipient's tissues. In oral cGVHD, the tissues in the mouth are damaged, causing painful mouth sores. Dexamethasone is a corticosteroid that is commonly used to treat inflammation. It is the only corticosteroid available that can be used as a mouth rinse.
Patients 12 years of age or older who have received a stem cell transplant may be eligible to participate if they are enrolled within 70 to 90 days of their transplant. Candidates are screened with a medical history and oral exam.
Participants are randomly assigned to receive either the dexamethasone rinse or a placebo (a solution that looks and tastes like the dexamethasone rinse but has no active medication). They undergo the following procedures:
Treatment with the study solution. Patients rinse their mouth with the dexamethasone solution or placebo three times a day for 3 months.
Clinic visits before starting treatment and at 1, 2 and 3 months after starting the study drug for the following procedures:
- Oral exam (before starting treatment and at each visit).
- Photographs of the mouth (before starting treatment and at 3 months).
- Biopsy from inside the cheek (before starting treatment). The inside of the cheek is numbed and a small piece of tissue is removed for examination by a pathologist.
- Saliva sample collection (before starting treatment).
- Blood draw (before starting treatment and at each visit).
- Quality-of-life questionnaires (before starting treatment and at 3 months).
- Questionnaire to assess level of dry mouth and mouth pain (before starting treatment and at each visit).
- Review of medications (at each visit).
- ACTH stimulation test to evaluate adrenal gland function (at 3 months). Patients are given an injection of a drug called "ACTH" or "cosynthropin," which is a version of a hormone normally produced by the pituitary gland. Blood samples are drawn before the injection and at 30 and 60 minutes after the injection to measure levels of the hormone cortisol.
After treatment ends, participants are contacted by telephone every month for 6 months to report any symptoms of cGVHD, and they return to the clinic at 6 months for a final evaluation.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Prevention
|Official Title:||Pilot Study of Topical Dexamethasone 0.01% Solution for Prevention of Oral Chronic Graft Versus Host Disease|
- Incidence of chronic oral GVHD [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Quality of life, systemic absorption of oral dexamethasone, effect on adrenocortical function. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||October 2006|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Drug: Dexamethasone 0.01% Solution
Prevention of oral GVHD by topical agents is an attractive strategy because it would potentially avoid the adverse effects associated with systemic immunosuppression. Topically administered dexamethasone solution is a commonly used agent for the treatment of oral inflammatory conditions including GVHD. However, the efficacy and systemic effects of topically administered dexamethasone solution are unknown. We therefore propose this trial designed to evaluate the efficacy and safety of topical dexamethasone solution for prevention of chronic oral GVHD in stem cell transplant recipients.
This phase II study will follow a randomized, double-blind, placebo controlled, parallel group design. Consenting subjects who have undergone hematopoietic stem cell transplantation at the NIH Clinical Center will be randomized 50/50 to receive dexamethasone 0.01% solution or placebo as an oral rinse for 3 months starting 90-100 days post-transplant. Subjects will be evaluated monthly after the start of intervention. Diagnostic and research evaluations will include a complete oral examination, oral mucosal biopsy prior to the beginning of the intervention (day -7) and at the time of development of oral GVHD or at the completion of intervention in the absence of clinical GVHD. We will measure serum dexamethasone levels and perform short cosyntropin (ACTH stimulation) test at the end of the 3-months of intervention or onset of clinically significant GVHD.
The primary objective of the study is to evaluate the safety and efficacy of topical dexamethasone 0.01% solution used as an oral rinse for prevention of oral chronic graft versus host disease. Our primary endpoint will be the proportion of subjects that develop clinically significant (severity score 3 or higher) oral chronic GVHD after three months.
Secondary objectives will include the impact of oral graft versus host disease on the quality of life, characterization of the changes in tissue and salivary biomarkers associated with development of oral graft versus host disease, and measures of the effects of topical dexamethasone on hypothalamo-pituitary-adrenal axis. Secondary outcomes will include oral cavity specific quality of life as measured by OHIP-14 questionnaire, oral discomfort levels, improvement in general quality of life scores, and severity of oral GVHD as measured by the site-specific GVHD scoring system.
|Contact: Catalina Ramos, R.N.||(301) firstname.lastname@example.org|
|Contact: Sawa Ito, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Sawa Ito, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|