Efficacy of Pirfenidone Plus MODD in Diabetic Foot Ulcers

NCT02632877 | Completed Phase 1

• 3 other identifiers: IBMMTG.14ISSSTE/CEI/TR/2014/01Institute of Molecular Biology
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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

Conditions

Diabetic Foot Ulcer

Keywords

pirfenidone; Modified oxide diallyl disulfide (MODD); ketanserin; diabetic foot ulcer

Outcome Measures

Primary Outcomes (1)

• assessing change of ulcerated area

  mm3

  1, 2, 3, 4, 5, and 6 months

Secondary Outcomes (9)

• mRNA levels of collagen type I alpha (COL-1a)

  0, 1 and 2 months

• mRNA levels of Transforming growth factor 1-beta (TGFb-1)

  0, 1 and 2 months

• mRNA levels of Transforming growth factor 3-beta (TGFb-3)

  0, 1 and 2 months

• mRNA levels of Vascular endothelial growth factor (VEGF)

  0, 1 and 2 months

• mRNA levels of Tumor necrosis factor alpha (TNFa)

  0, 1 and 2 months

Study Arms (2)

Pirfenidone with MODD

EXPERIMENTAL

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

Ketanserin

ACTIVE COMPARATOR

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

Interventions

Pirfenidone with MODD DRUG

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.

Also known as: KitosCell Q, 5-methyl-1-phenyl-2(1H)-pyridone with MODD

Pirfenidone with MODD

Ketanserin DRUG

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.

Also known as: sufrexal

Ketanserin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Guadalajara: lead
• Cell Pharma: collaborator

Study Sites (2)

Molecular Biology and Gene Therapy Institute

Guadalajara, Jalisco, 44340, Mexico

Location

Hospital Valentín Gómez Farías

Zapopan, Jalisco, Mexico

Location

MeSH Terms

Conditions

Diabetic Foot

Interventions

pirfenidone; Ketanserin

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Juan Armendariz-Borunda, PhD, FAASLD

  University of Guadalajara

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Molecular Biology and Genomics Department

Study Record Dates

• First Submitted: December 9, 2015
• First Posted: December 17, 2015
• Study Start: January 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 17, 2015

Record last verified: 2015-12

Locations

ME (2)