Topical Pentoxifylline Gel on Behcet's Disease Oral Ulcers

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

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.

Study Overview

• Status: Completed
• Conditions: Behçet Disease Affecting Oral Mucosa
• Intervention / Treatment: Drug: Colchicine; Drug: Pentoxifylline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi-Cerrahpaşa Tıp Fakültesi, İç Hastalıkları Anabilim Dalı-Romatoloji

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Ipekyolu Ilac Ltd. Sti
• Collaborators: Istanbul University - Cerrahpasa (IUC)
• Investigators: Principal Investigator: Gulen Hatemi, MD, İstanbul Üniversitesi-Cerrahpaşa

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2019
• Primary Completion (Actual): August 31, 2019
• Study Completion (Actual): September 30, 2019

Study Registration Dates

• First Submitted: March 21, 2019
• First Submitted That Met QC Criteria: March 22, 2019
• First Posted (Actual): March 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Eye Diseases; Genetic Diseases, Inborn; Stomatognathic Diseases; Mouth Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Vasculitis; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Behcet Syndrome; Oral Ulcer; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Antirheumatic Agents; Platelet Aggregation Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Gout Suppressants; Radiation-Protective Agents; Colchicine; Pentoxifylline
• Other Study ID Numbers: P104375V04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification will be available to other researchers.
• IPD Sharing Time Frame: Beginning 3 months following publication. No end date.
• IPD Sharing Access Criteria: Proposals should be directed to bderkunt@gmail.com. Anyone who provides a methodologically sound proposal will be approved to perform any type of analysis to achieve the aims in the proposals. To gain access, data requestors will need to sign a data access agreement. Data will be made available indefinitely at (link to be included).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No