Dexamethasone to Prevent Oral Chronic Graft-versus-Host Disease

Phase 2

Completed

Conditions: Graft vs Host Disease

Interventions: Drug: Placebo
Drug: Topical Dexamethasone

Registration Number: NCT00391170

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary: 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 "cosyntropin" 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.

Detailed Description: Prevention of oral chronic graft versus host disease (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 prophylaxis 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 oral chronic GVHD in stem cell transplant recipients.

This pilot 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 and the surrounding transplant clinics 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 chronic 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 GVHD. 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 chronic GVHD 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 Oral Health Impact Profile (OHIP)-14 questionnaire, oral discomfort levels, improvement in general quality of life scores, and severity of oral chronic GVHD as measured by the site-specific GVHD scoring system.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 62

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo oral rinse in stem cell transplant participants	Placebo	Placebo oral rinse in post allogeneic hematopoietic stem cell transplant participants. Rinse oral cavity three times daily for two minutes with ten milliliters then expectorate. Complete for three months duration.
Dexamethasone oral rinse in stem cell transplant participants	Topical Dexamethasone	Dexamethasone 0.01% (0.5mg/5 mL) oral rinse solution in post allogeneic hematopoietic stem cell transplant participants. Rinse oral cavity three times daily for two minutes with ten milliliters then expectorate. Complete for three months duration.

Primary Outcome Measures

Name	Time	Method
Participants That Developed Severity Score 3 or Higher Oral Chronic Graft Versus Host Disease (GVHD).	Day 90	Participants that developed clinically significant (severity score 3 or higher) oral chronic graft versus host disease (GVHD) within 90 days of initiating treatment. Oral chronic GVHD is defined by Lichen Planus (Oral GVHD) Severity Scale (Thongprasom et al., 2003). Score 5: White striae with erosive area \> 1 cm\^2 Score 4: White striae with erosive area \< 1 cm\^2 Score 3: White striae with erythematous area \> 1 cm\^2 Score 2: White striae with erythematous area \< 1 cm\^2 Score 1: Mild white striae only Score 0: No lesions, normal mucosa

Secondary Outcome Measures

Name	Time	Method
Participants With Chronic Oral Graft Versus Host Disease (GVHD) Based on Severity Scores	Day 90	Participants that developed oral chronic graft versus host disease (GVHD) within 90 days of initiating treatment. Oral chronic GVHD is defined by Lichen Planus (Oral GVHD) Severity Scale (Thongprasom et al., 2003). Score 5: White striae with erosive area \> 1 cm\^2 Score 4: White striae with erosive area \< 1 cm\^2 Score 3: White striae with erythematous area \> 1 cm\^2 Score 2: White striae with erythematous area \< 1 cm\^2 Score 1: Mild white striae only Score 0: No lesions, normal mucosa
Participants With Systemic Absorption of Topical Dexamethasone	3 months	Participants with systemic absorption of topical dexamethasone based on plasma dexamethasone level \< 30 ng/dL.
Participants With Suppressed Adrenal Cortical Function Due to Topical Dexamethasone	3 months	Number of participants who are not on systemic steroids with suppressed adrenal cortical function after completing study intervention phase (3 month) based on serum morning cortisol levels.