Effectiveness of Topical Thalidomide to Treat Chronic Graft-Versus-Host-Disease Related Stomatitis

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

This study was designed to be conducted in 2 parts. The first part is a pilot study to test the effects of topical thalidomide gel 20mg applied to up to 3 oral ulcers in patients who have developed oral chronic graft-versus-host-disease (cGVHD)-related ulcerative stomatitis following allogeneic bone marrow/peripheral blood stem cell transplant (HSCT). Chronic GVHD may be related to increased levels of a cytokine called TNF-alpha (TNFa) following HSCT. Thalidomide's anti-inflammatory effects may lower TNFa levels, lead to healing of these oral ulcers, and decrease oral pain.

If the pilot study is successful, the second part of the study will be done. This will test the effects of a 0.1% (20mg) thalidomide mouthwash in treating oral cGVHD-related stomatitis in patients following allogeneic HSCT. Applying thalidomide directly to the GVHD-related mouth ulcer in gel form or to the entire oral cavity in mouthwash form rather than taking it in pill form may reduce the amount of drug that enters the blood stream and cause less side effects.

In the pilot study, participants will be randomly assigned to receive thalidomide gel 20mg or placebo (identical gel with no thalidomide) to use 4 times a day for 4 weeks. In the mouthwash study, participants will be randomly assigned to receive 0.1% 20mg thalidomide mouthwash or placebo (identical mouth rinse with no thalidomide) to use 4 times a day for 4 weeks. Participants will undergo the following procedures before beginning experimental treatment, then once a week for 4 weeks, and then approximately 8 weeks after the first visit:

• Interview about current medications and use of alcohol and cigarettes
• Self-report of mouth and throat pain
• Oral examination for stomatitis rating, and oral ulcer(s) measurement
• Quality of life questionnaire (repeated only at week 8 of the study)
• Mouth photography to measure and record the oral ulcer response to treatment
• Saliva sampling to look for proinflammatory cytokines (small proteins), including TNFa
• Oral ulcer exudate collected by filter paper to obtain fluid for measuring TNFa levels
• Gentle swabbing of oral ulcers to culture for virus, fungus, and bacteria that may be present
• Small punch biopsy of the area near the ulcer or affected area to check for presence of TNFa (repeated only at week 4 of the study)
• Blood sampling to monitor TNFa levels
• A urine pregnancy test for women who are able to have children (repeated at weeks 2, 4, and 8)

Condition or disease	Intervention/treatment	Phase
Graft-versus-Host Disease; Stomatitis	Drug: Thalidomide Gel; Drug: Placebo Gel	Phase 2

  Show Detailed Description

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	Evaluation of Efficacy and Mechanisms of Topical Thalidomide for Chronic Graft-Versus-Host-Disease Related Stomatitis
Study Start Date :	December 2003
Actual Primary Completion Date :	April 2010
Actual Study Completion Date :	April 2010

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Thalidomide gel; Thalidomide gel 20 mg applied topically 4 times daily for 4 weeks to a maximum of 3 target oral ulcers	Drug: Thalidomide Gel
Experimental: Placebo; Placebo gel with no Thalidomide applied topically 4 times daily for 4 weeks to a maximum of 3 target oral ulcers	Drug: Placebo Gel

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Mean Percentage Change in Total Surface Area of Oral Ulceration. [ Time Frame: baseline to 4 weeks ]
   Mean percentage change in total surface area of oral ulceration

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

• INCLUSION CRITERIA:

Participating in HSCT or cGVHD protocols and willing to participate in this study concurrently;

Diagnosed with oral cGVHD stomatitis confirmed by surgical biopsy results;

Oral ulceration present

Able to understand and sign protocol informed consent;

Ages 18 to 80 years of age.

EXCLUSION CRITERIA:

Pregnant or lactating females;

For the proof of concept study, females who are not surgically sterilized by means of hysterectomy or tubal ligation;

For the main study, females of childbearing potential who do not agree to the use of two forms of highly effective contraception for at least four weeks prior, during, and for four weeks following the last dose of study drug;

Sexually active males who do not agree to the use of a latex condom while receiving study drug and for four weeks following the last dose of study drug;

Unwilling to follow precautions for use of thalidomide;

Unable to demonstrate appropriate use of study medication;

Concurrent use of non-protocol-related medications confounding assessment of the inflammatory response (antihistamines, non-steroidal anti-inflammatory drugs);

Allergic reaction to thalidomide;

Pre-existing oral infection, which might maximize the possibility of an infection or sepsis contributing to a drug-related adverse event;

Unwilling or unable to forego concurrent treatment for mucosal lesions and/or related oral pain (including topical steroids, viscous lidocaine, topical anti-fungals);

Requiring addition of new systemic therapy including thalidomide, steroids, or radiation therapy;

Use of sedatives (including CNS depressants);

Absolute neutrophil count (ANC) less than 750/mm(3)

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 28104

Sponsors and Collaborators

National Institute of Nursing Research (NINR)

Fred Hutchinson Cancer Research Center

Investigators

Principal Investigator:	Jane Fall-Dickson, RN, PhD	NIH/NINR

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Albandar JM, Brunelle JA, Kingman A. Destructive periodontal disease in adults 30 years of age and older in the United States, 1988-1994. J Periodontol. 1999 Jan;70(1):13-29. Erratum in: J Periodontol 1999 Mar;70(3):351.

Antin JH, Ferrara JL. Cytokine dysregulation and acute graft-versus-host disease. Blood. 1992 Dec 15;80(12):2964-8. Review.

Aucott DM, Ashley FP. Assessment of the WHO partial recording approach in identification of individuals highly susceptible to periodontitis. Community Dent Oral Epidemiol. 1986 Jun;14(3):152-5.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

St John L, Gordon SM, Childs R, Marquesen M, Pavletic SZ, Wu TX, Cozzarelli T, Schroeder E, Saria MG, Fall-Dickson JM. Topical thalidomide gel in oral chronic GVHD and role of in situ cytokine expression in monitoring biological activity. Bone Marrow Transplant. 2013 Apr;48(4):610-1. doi: 10.1038/bmt.2012.178. Epub 2012 Sep 24.

Responsible Party:	National Institute of Nursing Research (NINR)
ClinicalTrials.gov Identifier:	NCT00075023 History of Changes
Other Study ID Numbers:	040069; 04-NR-0069
First Posted:	December 31, 2003
Results First Posted:	November 4, 2015
Last Update Posted:	November 4, 2015
Last Verified:	October 2015

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Nursing Research (NINR) ):

Stomatitis; Oropharyngeal pain; TNF-alpha; Allogeneic hematopoietic stem cell transplant	Inflammation; Thalidomide; Oral chronic graft-versus-host disease

Additional relevant MeSH terms:

Graft vs Host Disease; Stomatitis; Immune System Diseases; Mouth Diseases; Stomatognathic Diseases; Thalidomide; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs	Leprostatic Agents; Anti-Bacterial Agents; Anti-Infective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antineoplastic Agents