Topical Pentoxifylline Gel on Behcet's Disease Oral Ulcers

Study Overview
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Brief Summary
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Although Behçet's Disease (BD) has no FDA-approved therapies, numerous clinical reports suggest that oral ulcers of BD may resolve when treated with systemic ingested pentoxifylline (PTX). The investigators here propose to investigate the therapeutic potential of PTX dissolved in muco-adherent formulation and directly applied to the oral lesions. This 60 patient proof of concept trial is designed to meet regulatory requirements for safety concerns while at the same time exploring the potential efficacy and clinical utility of this product. The investigators hypothesize that application of topical PTX will accelerate the healing of these lesions in a clinically meaningful way, and further hypothesize that topical PTX can become a valuable adjunct to any other systemic therapy for BD.

Detailed Description
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Behçet's Clinic at Cerrahpaşa Medical Faculty at the University of Istanbul has a long history of supportive care for BD patients and is recognized as the world leader in this regard. According to the EULAR 2018 recommended guidelines of Behcet's Disease, the first line of therapy recommended against recurring oral ulcers is colchicine. However, a significant portion of the participants undergoing colchicine therapy does not have sufficient response and require subsequent immune modulatory therapy. By comparing participants receiving colchicine as part of supportive care to those who also receive topical pentoxifylline (PTX), the investigators seek to prove the concept that topical PTX may have clinical value. Additionally, the investigators seek to demonstrate the safety and practicality of using topical PTX in BD patients. If the PTX gel therapy provides a sufficient response in participants, these participants might not need to undergo immune modulatory therapies. The risks of PTX are well characterized and previously reported adverse events were primarily gastrointestinal. The investigators expect fewer GI symptoms to result from the topical PTX application. The investigators anticipate the benefits of PTX can be optimized by a topical application, but require a trial to test that hypothesis.

Official Title
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Clinical Protocol for Administration of Topical Pentoxifylline Gel on Behcet's Disease Oral Ulcers

Conditions
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Behçet Disease Affecting Oral Mucosa

Intervention / Treatment
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* Drug: Pentoxifylline
* Drug: Colchicine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets the International Study Group criteria for Behcet's Disease Presents with at least one active lesions accessible to measurement, the largest of which is to be designated as the index ulcer Index oral ulcer to be assessed should be in the easily accessible areas of the oral mucosa, and the oral ulcer first began within 48 hrs prior to enrollment Adult (>18 years) male or a non-pregnant, non-lactating female Has signed an Ethics Committee (EC) approved subject consent form Has completed all screening procedures satisfactorily, is deemed to be an acceptable subject and is otherwise eligible for entry into the study Is willing and able to comply with the protocol Is being treated with colchicine Exclusion Criteria: Has a severe, acute, or chronic systemic disease other than Behcet's Disease such as congestive heart failure, hepatic failure, renal failure, systemic lupus erythematosus, Stevens-Johnson syndrome, ulcerative colitis, cancer, leukemia, diabetes, AIDS, or any other condition that is severely compromising the immune system Has received pentoxifylline in any form over the previous 60 days prior to enrollment Has experienced recent cerebral and/or retinal hemorrhage or in patients who have previously exhibited intolerance to pentoxifylline or methylxanthines such as caffeine, theophylline, and theobromine Has concomitant administration of strong CYP1A2 inhibitors (including e.g. ciprofloxacin or fluvoxamine) and other drugs that may increase the exposure to pentoxifylline Is receiving immune suppressing or modulating therapy (e.g., apremilast) or topical corticosteroids within 2 weeks prior to enrollment Is not being treated with colchicine Is under active treatment for dental conditions, such that multiple dental office visits would be required during the study period, or presents with oral conditions which are not thought to be related to Behcet's Disease and in the judgment of a qualified dentist, will require treatment during the study period Is suffering from any medical condition other than Behcet's Disease known to cause oral ulcerations, such as erosive lichen planus, benign mucous membrane pemphigoid, Systemic Lupus Erythematous, Crohn's disease, Reiter's syndrome, or AIDS. Has an eating disorder and/or psychiatric illness requiring treatment. Has a history of, or is currently exhibiting, any disease or condition, which, in the opinion of the principal investigator, would place the subject at increased risk during study therapy. Has any abnormality in hematological or biochemical variable, which, in the opinion of the principal investigator, would place the subject at increased risk during study therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Colchicine<br>Colchicine therapy as part of supportive care routinely offered in Behcet's Clinic-Istanbul | Drug: Colchicine<br>* Colchicine therapy is provided to patients with oral ulcers as part of supportive care routinely offered by Behcet's Clinic-Istanbul.<br>* Other names: Colchicum-Dispert;|
| Experimental: Topical Pentoxifylline Gel and Colchicine<br>Topical Pentoxifylline Gel administration in addition to the colchicine therapy as part of supportive care routinely offered in Behcet's Clinic-Istanbul | Drug: Pentoxifylline<br>* Topical gel version of pentoxifylline to be administered intraorally.<br>* Other names: Trental;Drug: Colchicine<br>* Colchicine therapy is provided to patients with oral ulcers as part of supportive care routinely offered by Behcet's Clinic-Istanbul.<br>* Other names: Colchicum-Dispert;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in the speed of healing of the index oral ulcer | The size of the index oral ulcer will be measured at study enrollment and during the two week trial at seven time points (Please see Schedule of Activities in the protocol for more detail). The change in the size of the index ulcer will be compared between two study arms. | The participants will be assessed at seven time points starting at enrollment when the index ulcer is assigned until the complete healing(disappearance) of the index oral ulcer. This time frame is estimated to take two weeks (please see SoA in protocol). | 
| Mean change in the total number of oral ulcers | The total number of oral ulcer will be measured at study enrollment and during the two week trial at seven time points (Please see Schedule of Activities in the protocol for more detail). The total number of oral ulcers will be compared between two study arms. | The participants will be assessed at seven time points starting at the enrollment visit until the end of study visit. This time frame is estimated to take two weeks. | 
| Mean change in patient reported outcome pain scores | Pain scores will be compared between two study arms as measuring pain offers an opportunity to correlate simple measurements of oral mucosal disruption with patient's fundamental disease experience. | The participants will be assessed at sixteen time points starting at the enrollment visit until the final follow up visit.This time frame is estimated to take 45 days. Please see Schedule of Activities(SoA) in the protocol. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behcet's Disease-Quality of Life Assessment Questionnaire | Participant's quality of life will be assessed by a Behcet's Disease specific questionnaire prepared by key opinion leaders in the field of Behcet's Disease research at the University of Leeds. Please see the Behcet's Disease Quality of Life Measure in the appendix of the protocol for more details. | The participants will be assessed at eight time points starting at the enrollment visit until the final follow up visit.This time frame is estimated to take 45 days. Please see Schedule of Activities(SoA) in the protocol. | 
| Behcet's Disease Activity Index | Behcet's Disease Activity Index is prepared by International Society for Behcet's Disease to guide the doctor in assessing the disease activity. | The participants will be assessed at eight time points starting at the enrollment visit until the final follow up visit.This time frame is estimated to take 45 days. Please see Schedule of Activities(SoA) in the protocol. |