Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Topical Pentoxifylline Gel on Behcet's Disease Oral Ulcers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03888846
Recruitment Status : Recruiting
First Posted : March 25, 2019
Last Update Posted : May 24, 2019
Sponsor:
Collaborator:
Istanbul University-Cerrahpasa School of Medicine
Information provided by (Responsible Party):
Ipekyolu Ilac Ltd. Sti

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Behçet Disease Affecting Oral Mucosa Drug: Pentoxifylline Drug: Colchicine Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Protocol for Administration of Topical Pentoxifylline Gel on Behcet's Disease Oral Ulcers
Actual Study Start Date : March 25, 2019
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : July 2019


Arm Intervention/treatment
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 Name: 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: Pentoxifylline
Topical gel version of pentoxifylline to be administered intraorally.
Other Name: Trental

Drug: Colchicine
Colchicine therapy is provided to patients with oral ulcers as part of supportive care routinely offered by Behcet's Clinic-Istanbul.
Other Name: Colchicum-Dispert




Primary Outcome Measures :
  1. Mean change in the speed of healing of the index oral ulcer [ Time Frame: 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). ]
    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.

  2. Mean change in the total number of oral ulcers [ Time Frame: 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. ]
    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.

  3. Mean change in patient reported outcome pain scores [ Time Frame: 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. ]
    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.


Secondary Outcome Measures :
  1. Behcet's Disease-Quality of Life Assessment Questionnaire [ Time Frame: 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. ]
    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.

  2. Behcet's Disease Activity Index [ Time Frame: 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 is prepared by International Society for Behcet's Disease to guide the doctor in assessing the disease activity.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03888846


Contacts
Layout table for location contacts
Contact: Semsi B Derkunt, PhD 631-219-6223 bderkunt@gmail.com

Locations
Layout table for location information
Turkey
Istanbul Universitesi-Cerrahpaşa Tıp Fakültesi, İç Hastalıkları Anabilim Dalı-Romatoloji Recruiting
Istanbul, Turkey, 34098
Contact: Mine Batumlu    (+90)-542-432-9769    minebatumlu@hotmail.com   
Principal Investigator: Gulen Hatemi, MD         
Sponsors and Collaborators
Ipekyolu Ilac Ltd. Sti
Istanbul University-Cerrahpasa School of Medicine
Investigators
Layout table for investigator information
Principal Investigator: Gulen Hatemi, MD Istanbul Universitesi-Cerrahpasa
  Study Documents (Full-Text)

Documents provided by Ipekyolu Ilac Ltd. Sti:

Layout table for additonal information
Responsible Party: Ipekyolu Ilac Ltd. Sti
ClinicalTrials.gov Identifier: NCT03888846     History of Changes
Other Study ID Numbers: P104375V04
First Posted: March 25, 2019    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All of the individual participant data collected during the trial, after deidentification will be available to other researchers.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Beginning 3 months following publication. No end date.
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).

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Behcet Syndrome
Oral Ulcer
Mouth Diseases
Stomatognathic Diseases
Uveitis, Anterior
Panuveitis
Uveitis
Uveal Diseases
Eye Diseases
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Hereditary Autoinflammatory Diseases
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases
Skin Diseases, Vascular
Colchicine
Pentoxifylline
Gout Suppressants
Antirheumatic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Platelet Aggregation Inhibitors
Radiation-Protective Agents