Dexamethasone to Prevent Oral Chronic Graft-versus-Host Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
ClinicalTrials.gov Identifier:
NCT00391170
First received: October 20, 2006
Last updated: July 9, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Graft vs Host Disease
Drug: Topical Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Pilot Study of Topical Dexamethasone 0.01% Solution for Prevention of Oral Chronic Graft Versus Host Disease

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Proportion with & gt; = Grade 3 oral GVHD [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Scale for Oral Pain [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • GVHD Severity Scale [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 106
Study Start Date: October 2006
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active
Dexamethasone 0.01%
Drug: Topical Dexamethasone
N/A
Placebo Comparator: Placebo
Placebo oral rinse

Detailed Description:

Prevention of oral chronic graft verusu 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 oral 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 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 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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. History of allogeneic hematopoietic stem cell transplantation at the NIH Clinical Center 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00391170

Contacts
Contact: Richard W Childs, M.D. (301) 451-7128 childsr@nhlbi.nih.gov
Contact: Sawa Ito, M.D. (301) 326-5233 itos2@mail.nih.gov

Locations
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    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Sawa Ito, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
ClinicalTrials.gov Identifier: NCT00391170     History of Changes
Other Study ID Numbers: 070005, 07-H-0005
Study First Received: October 20, 2006
Last Updated: July 9, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Oral Chronic GVHD
Topical Dexamethasone
Tissue Markers
Salivary Proteomics
Quality of Life
Oral Chronic Graft Versus Host Disease
Oral Pain
Mouth Pain

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014