Efficacy of Pirfenidone Plus MODD in Diabetic Foot Ulcers

December 14, 2015 updated by: Juan Armendáriz-Borunda, University of Guadalajara

Efficacy of Pirfenidone Gel Combined With Modified Oxide Diallyl Disulfide (MODD) Versus Ketanserin for the Treatment of Diabetic Foot Ulcers

Diabetic foot ulcers (DFU) develop because of the interaction of predisposing factors like neuropathy, angiopathy and infection. Likewise, environmental factors like lesion hygiene, diet and life style.

DFU results as a complication in diabetic patients and it is the most common cause of non-traumatic foot amputation in people older than 50 years. Foot amputation decreases patients´ quality of life since only 33% of them will continue walking with the use of a prothesis.

However, 30% of patients subjected to amputation will die in the first year after surgery and by the 5th year, post-surgery 50% of them will need the amputation of the remaining body extremity.

According to the World Foundation for Diabetes, in Latin America there are 18 million people with Diabetes Mellitus Type 2 (DM2). This number will increase in the next 20 years to 30 million.

Medical expenses for diabetic patients are calculated to be around 8,000 million dollars, annually. In Mexico, according to the Mexican Federation for Diabetes there are 6.5-10 millions of diabetic patients.

Amputation due to DFU complications has many social and economic implications. In Mexico in 2011 diabetes mellitus complications were the principal cause of death in the institute of mexican social security (IMSS) population.

On the other hand, 5-methyl-1-phenyl-2-(1h)-pyridone (PFD) is considered an anti-inflammatory drug that promotes re-epithelization due to fibroblast stimulation, angiogenesis and vasculogenesis during tissue remodeling.

According to this, the investigators believe that PFD could play an important role in DFU resolution and for this reason, the investigators consider necessary to analyze the efficacy of 5-methyl-1-phenyl-2-(1h)-pyridone for the treatment of DFU since it has showed improvement in chronic skin ulcers in pilot studies.

Nowadays, DFU treatment includes management of metabolism, angiopathy and neuropathy along with broad-spectrum antibiotic therapy. However, several reports indicate it is insufficient for and adequate control of diabetic patients.

Then, it is important to develop efficient therapies for the treatment of DFU. In this context, Ketanserin (Sufrexal™) is a drug to induce scar formation. It has been demonstrated to decrease peripheral vascular resistance, platelet aggregation and improves hemorheologic parameters.

Topical administration of ketanserin has showed beneficial effects in inflammation, granulation and epithelization.

Since these two drugs have showed beneficial effects in tissue regeneration, the investigators believe it is important to compare their safety and efficacy for the treatment of DFU

Study Overview

Status

Completed

Conditions

Detailed Description

Subjects will be randomized using a random number table to distribute in the control (ketanserin) and the experimental group (PFD+MODD). Demographics data and medical history will be registered on a monthly basis, relative ulcer volume will be calculated by measuring the longest, widest and deepest ulcer side with sterile flexible graduated ruler. The ulcer will be classified according to Wagner scale and photographs will be taken. Ulcer area will be washed with aseptic solution (accua aseptic solution™) and a biopsy of around 10-15 mm3 will be taken from the middle of the ulcer using a scalpel blade. Patients in the experimental group will receive topical PFD+MODD (8% gel) three times a day and patients in control group will receive ketanserin (2% cream) twice a day. Both groups will apply the medicament for six months previous cleansing of the area. Biopsies will be taken at the beginning, at month one and month two. After this time, only photographs will be performed, and relative ulcer volume will be measured. 5 ml of blood will be taken at the beginning and the end of the study to measure general clinical parameters.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44340
        • Molecular Biology and Gene Therapy Institute
      • Zapopan, Jalisco, Mexico
        • Hospital Valentín Gómez Farías

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnostic for diabetic foot ulcer grade I to II according to Wagner scale
  • Volunteer patients that accept to sign an informed consent letter
  • Patients that agree to fill a clinical history, access to physical exploration and biochemical analysis samples, ulcer biopsy and photodocumentation of ulcer progress.
  • Patients willing to sign a compliance letter to apply treatment as indicated by the principal investigator.

Exclusion Criteria:

  • Patients with another chronic disease like venous insufficiency or cardiopathy.
  • Patients with severe arteriopathy that do not have possibility to direct revascularization like the ones subject to graft tissue, plastics or stents positioning.
  • Patients with severe arteriopathy that do not have possibility to indirect vascularization like the ones subject to sympathectomy .

Elimination criteria:

  • Patients without adherence to treatment
  • Patients that miss medical appointments
  • Patients that show allergy to the 8% 5-methyl-1-phenyl-2-(1h pyridone gel and MODD or any of its components.
  • Patients allergic to the 2% ketanserin gel or any of its components.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pirfenidone with MODD

Active ingredients: Pirfenidone 8% with modified oxide diallyl disulfide (MODD) 0.016%.

Dosage form: gel. Dosage: standar finger tip unit (0.5g for an area of 100 to 120 square centimeters).

Frequency and duration: topically applied every eight hours for 6 months.

Patients with diabetic foot ulcer will be treated three times a day with a smooth layer (standar finger tip unit 0.5g for an area of 100 to 120 square centimeters) of KitosCell Q (Pirfenidone with MODD) in form of gel and the wound will be covered with a bandage.
Other Names:
  • KitosCell Q
  • 5-methyl-1-phenyl-2(1H)-pyridone with MODD
Active Comparator: Ketanserin

Active ingredients: Ketanserin 2%. Dosage form: gel. Dosage: standar finger tip unit (0.5g for an area of 100 to 120 square centimeters).

Frequency and duration: topically applied every 12 hours for 6 months.

Patients will be administered ketanserin twice a day usign the standar finger tip unit (0.5g for an area of 100 to 120 square centimeters) and the wound will be covered with a bandage. This arm is a control for evolution of diabetic foot ulcer.
Other Names:
  • sufrexal

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
assessing change of ulcerated area
Time Frame: 1, 2, 3, 4, 5, and 6 months
mm3
1, 2, 3, 4, 5, and 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
mRNA levels of collagen type I alpha (COL-1a)
Time Frame: 0, 1 and 2 months
expression relative units
0, 1 and 2 months
mRNA levels of Transforming growth factor 1-beta (TGFb-1)
Time Frame: 0, 1 and 2 months
expression relative units
0, 1 and 2 months
mRNA levels of Transforming growth factor 3-beta (TGFb-3)
Time Frame: 0, 1 and 2 months
expression relative units
0, 1 and 2 months
mRNA levels of Vascular endothelial growth factor (VEGF)
Time Frame: 0, 1 and 2 months
expression relative units
0, 1 and 2 months
mRNA levels of Tumor necrosis factor alpha (TNFa)
Time Frame: 0, 1 and 2 months
expression relative units
0, 1 and 2 months
mRNA levels of Hypoxia-inducible factor 1-alpha (HIF-1a)
Time Frame: 0, 1 and 2 months
expression relative units
0, 1 and 2 months
mRNA levels of Hypoxia-inducible factor 1-betha (HIF-1b)
Time Frame: 0, 1 and 2 months
expression relative units
0, 1 and 2 months
mRNA levels of Keratinocyte Growth Factor (KGF)
Time Frame: 0, 1 and 2 months
expression relative units
0, 1 and 2 months
mRNA levels of Matrix metalloproteinase-1 (MMP-1)
Time Frame: 0, 1 and 2 months
expression relative units
0, 1 and 2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Study Director: Juan Armendariz-Borunda, PhD, FAASLD, University of Guadalajara

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

December 9, 2015

First Submitted That Met QC Criteria

December 14, 2015

First Posted (Estimate)

December 17, 2015

Study Record Updates

Last Update Posted (Estimate)

December 17, 2015

Last Update Submitted That Met QC Criteria

December 14, 2015

Last Verified

December 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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