Dexamethasone to Prevent Oral Chronic Graft-versus-Host Disease
Condition: Graft vs Host Disease
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Topical Dexamethasone; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): dexamethasone 0.01%; Placebo
Intervention MeSH terms: Dexamethasone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Oral Chronic GVHD; Topical Dexamethasone; Tissue Markers; Salivary Proteomics; Quality of Life; Oral Chronic Graft Versus Host Disease; Oral Pain; Mouth Pain