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Efficacy of Pirfenidone Plus MODD in Diabetic Foot Ulcers

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ClinicalTrials.gov Identifier: NCT02632877
Recruitment Status : Completed
First Posted : December 17, 2015
Last Update Posted : December 17, 2015
Sponsor:
Collaborator:
Cell Pharma
Information provided by (Responsible Party):
Juan Armendáriz-Borunda, University of Guadalajara

Brief Summary:

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


Condition or disease Intervention/treatment Phase
Diabetic Foot Ulcer Drug: Pirfenidone with MODD Drug: Ketanserin Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Efficacy of Pirfenidone Gel Combined With Modified Oxide Diallyl Disulfide (MODD) Versus Ketanserin for the Treatment of Diabetic Foot Ulcers
Study Start Date : January 2014
Actual Primary Completion Date : November 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Pirfenidone

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.

Drug: Pirfenidone with MODD
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.

Drug: Ketanserin
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 Name: sufrexal




Primary Outcome Measures :
  1. assessing change of ulcerated area [ Time Frame: 1, 2, 3, 4, 5, and 6 months ]
    mm3


Secondary Outcome Measures :
  1. mRNA levels of collagen type I alpha (COL-1a) [ Time Frame: 0, 1 and 2 months ]
    expression relative units

  2. mRNA levels of Transforming growth factor 1-beta (TGFb-1) [ Time Frame: 0, 1 and 2 months ]
    expression relative units

  3. mRNA levels of Transforming growth factor 3-beta (TGFb-3) [ Time Frame: 0, 1 and 2 months ]
    expression relative units

  4. mRNA levels of Vascular endothelial growth factor (VEGF) [ Time Frame: 0, 1 and 2 months ]
    expression relative units

  5. mRNA levels of Tumor necrosis factor alpha (TNFa) [ Time Frame: 0, 1 and 2 months ]
    expression relative units

  6. mRNA levels of Hypoxia-inducible factor 1-alpha (HIF-1a) [ Time Frame: 0, 1 and 2 months ]
    expression relative units

  7. mRNA levels of Hypoxia-inducible factor 1-betha (HIF-1b) [ Time Frame: 0, 1 and 2 months ]
    expression relative units

  8. mRNA levels of Keratinocyte Growth Factor (KGF) [ Time Frame: 0, 1 and 2 months ]
    expression relative units

  9. mRNA levels of Matrix metalloproteinase-1 (MMP-1) [ Time Frame: 0, 1 and 2 months ]
    expression relative units



Information from the National Library of Medicine

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

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.

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): NCT02632877


Locations
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Mexico
Molecular Biology and Gene Therapy Institute
Guadalajara, Jalisco, Mexico, 44340
Hospital Valentín Gómez Farías
Zapopan, Jalisco, Mexico
Sponsors and Collaborators
University of Guadalajara
Cell Pharma
Investigators
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Study Director: Juan Armendariz-Borunda, PhD, FAASLD University of Guadalajara

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Responsible Party: Juan Armendáriz-Borunda, Head, Molecular Biology and Genomics Department, University of Guadalajara
ClinicalTrials.gov Identifier: NCT02632877     History of Changes
Other Study ID Numbers: IBMMTG.14
ISSSTE/CEI/TR/2014/01 ( Other Identifier: ISSSTE )
Institute of Molecular Biology ( Other Identifier: University of Guadalajara )
First Posted: December 17, 2015    Key Record Dates
Last Update Posted: December 17, 2015
Last Verified: December 2015
Keywords provided by Juan Armendáriz-Borunda, University of Guadalajara:
pirfenidone
Modified oxide diallyl disulfide (MODD)
ketanserin
diabetic foot ulcer
Additional relevant MeSH terms:
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Diabetic Foot
Foot Ulcer
Ulcer
Pathologic Processes
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Leg Ulcer
Skin Ulcer
Skin Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Diabetic Neuropathies
Foot Diseases
Pirfenidone
Diallyl disulfide
Ketanserin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents
Antihypertensive Agents
Platelet Aggregation Inhibitors
Serotonin Antagonists