Dexamethasone to Prevent Oral Chronic Graft-versus-Host Disease
Condition: Graft vs Host Disease
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: Topical Dexamethasone; Placebo
Intervention description: dexamethasone 0.01%; Placebo
Intervention MeSH terms: Dexamethasone
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 62.0
Sex: All
Minimum age: 12 Years
Maximum age: 110 Years
Healthy volunteers: No
Keywords: Oral Chronic GVHD; Topical Dexamethasone; Tissue Markers; Salivary Proteomics; Quality of Life; Oral Chronic Graft Versus Host Disease; Oral Pain; Mouth Pain

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. History of allogeneic hematopoietic stem cell transplantation within 60-90 days
                  of enrollment.

               2. Age 12 or older.

               3. Ability to rinse and expectorate study medication rather than swallow it.

               4. Ability and willingness to come to Clinical Center for follow-up appointments and
                  at the time of development of symptoms/signs suggestive of oral GVHD.

        EXCLUSION CRITERIA:

          1. Clinically significant oral chronic GVHD at the time of the screening.

          2. Active viral or fungal infection involving oral cavity not resolving by day 90.

          3. Platelet count less than 20,000/ml at the time of the screening appointment.

          4. Life expectancy less than 4 months at the time of enrollment.

          5. Documented hypersensitivity to dexamethasone.

          6. Pregnancy or lactation.

          7. Inability to understand the investigational nature of the study.

          8. Inability to provide informed consent.