The Effect of Combination Therapy of Oral MB and PRP-FG in Patients With Non-healing Diabetic Foot Ulcer

Early Phase 1

Recruiting

• Conditions: Diabetic Foot Ulcers; Diabetic Wound
• Interventions: Other: Milk and Platelet-Rich Plasma-Fibrin Glue (control); Drug: Methylene Blue and Platelet-Rich Plasma-Fibrin Glue; Other: Milk (control); Drug: Methylene Blue

• Registration Number: NCT05850611
• Lead Sponsor: Mashhad University of Medical Sciences

Brief Summary

The aim of this study is to evaluate the chance of non-healing diabetic foot ulcers repair by improving the condition of lack of oxygen or hypoxia in the wound area caused by diabetes using methylene blue along with the use of platelet-rich plasma-fibrin glue as an effective treatment for wound healing.

Detailed Description

The current study assesses the effects of methylene blue along with the use of platelet-rich plasma-fibrin glue on wound healing in patients with nonhealing diabetic foot ulcers (non-healing DFU). This randomized controlled trial is performed on 20 patients with non-healing DFU. Patients were treated with PRP-FG dressing plus 200 ml of oral methylene blue dissolved in milk(intervention group) or PRP-FG dressing plus placebo (200 ml of milk) (control group) for 4 weeks.

Study Timeline

• Study First Submitted: 2023-03-06
• Study Start: 2023-04-30
• Study First Submitted QC: 2023-04-30
• Study First Posted: 2023-05-09
• Primary Completion: 2023-08-21
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-03
• Last Update Posted: 2023-10-04
• Study Completion: 2024-09-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Having a Diabetic ulcer grade II and IV based on Wagner's classification on the sole, medial, or lateral part of the foot (including all surfaces of the toes)
• Having a single ulcer on the feet and extremities (toes, soles, heels) with no significant reduction in ulcer size (<20%) despite the use of best treatment methods for at least four weeks
• If there is more than one non-healing wound, choose the largest wound
• The size of the wound surface (length × width) between 2 cm2 and 20 cm2
• No smoking, alcohol, and drug addiction based on the patient's self-report
• Not taking drugs that may interfere with wound healing, such as Corticosteroids, immunosuppressants, and cytotoxic agents
• Not having a concurrent chronic disease that may cause problems in wound healing, such as cancers, vasculitis, no history of known severe kidney, liver, and heart disease, such as liver cirrhosis, active hepatitis, dialysis, etc.
• Not taking antidepressants
• Insensitivity to milk lactose
• Not having Glucose 6-phosphate dehydrogenase (G6PD) deficiency
• Confirmed, informed, signed consent form
• Ankle Brachial Index (ABI) higher than or equal to 0.7

Exclusion Criteria

• Do not be treated with methylene blue
• The confirmed presence of osteomyelitis, or if there is suspicion of osteomyelitis
• The subject is pregnant or intends to become pregnant during the test period
• The patient is known to have mental, developmental, physical, and emotional disorders
• The occurrence of certain medical conditions
• The presence of a wound with a clear and severe infection, which is characterized by significant purulent secretions or extensive cellulitis, or gangrene requiring amputation
• Evidence of venous, ischemic, neurotrophic ulcers (numbness, tingling, lack of Achilles tendon reflex) and traumatic wounds in the patient
• Failure to refer the patient more than two times to the mentioned center for follow-up and dressing change
• Hypersensitivity reaction to methylene blue
• Platelet count less than 100,000
• The patient's lack of consent to continue cooperation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Milk and Platelet-Rich Plasma-Fibrin Glue (control)	Milk and Platelet-Rich Plasma-Fibrin Glue (control)	Patients with non-healing Diabetic Foot Ulcers will be treated with PRP-Fibrin-Glue and 200 ml of milk for 4 weeks.
Methylene Blue and Platelet-Rich Plasma-Fibrin Glue	Methylene Blue and Platelet-Rich Plasma-Fibrin Glue	Patients with non-healing Diabetic Foot Ulcers will treat with PRP-Fibrin-Glue plus oral methylene blue (70 mg in 200 ml of milk) for 4 weeks.
Milk (control)	Milk (control)	Patients with non-healing Diabetic Foot Ulcers only will receive 200 ml of milk for 4 weeks.
Methylene Blue	Methylene Blue	The first intervention group (group A) includes diabetic patients with chronic foot ulcers who, despite common treatments, will be undergone oral methylene blue intervention (70 mg in 200 ml of milk) for 4 weeks.

Primary Outcome Measures

Name	Time	Method
Wound Size	4 weeks	Wound size will be measured with a ruler for length, and width as well as with digital imaging. Wound size will be assessed in digital images taken of the wound.
The healing rate of the ulcer	4 weeks	Measurement of wound area with a ruler

Secondary Outcome Measures

Name	Time	Method
Platelet count at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Blood pressure (systolic and diastolic)	4 weeks	The pressure of the blood in the circulatory system
Serum IL-6 levels at baseline and after the intervention	4 weeks	Analysis of serum interleukin-6 (IL-6) levels
Serum FBS levels at baseline and after the intervention	4 weeks	Analysis of serum fasting blood sugar (FBS ) levels
Serum Insulin levels at baseline and after the intervention	4 weeks	Analysis of Insulin levels
Lipid Profile at baseline and after the intervention	4 weeks	Serum Triglyceride, Cholesterol, HDL, LDL, VLDL
Serum Creatinine at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum total bilirubin at baseline and after the intervention	4 weeks	In a quantitative laboratory method
HbA1c at baseline and after the intervention	4 weeks	Glycated hemoglobin
Uric Acid levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum Homocysteine levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum AST (Aspartate Transferase) levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
TcPO2 at baseline and after the intervention	4 weeks	Transcutaneous oxygen tension (TcpO2) provides information about blood perfusion in the tissue immediately below the skin. (blood pressure, measured in millimeters of mercury (mmHg))
Oxygen saturation at baseline and after the intervention	4 weeks	Blood must contain a normal concentration of hemoglobin. that hemoglobin must be \>95 % saturated with oxygen in arterial blood (sO2(a) \>95 %)
Serum TNF-α levels at baseline and after the intervention	4 weeks	Analysis of serum tumor necrosis factor α (TNFα) levels
Serum Vitamin D levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum ALP (alkaline phosphatase) levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Nitric oxide blood at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum lactate dehydrogenase (LDH) levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
The resting systolic toe pressure (TP) at baseline and after the intervention	4 weeks	The toe cuff with the sphygmomanometer is slowly inflated until the waveform flattens (generally between 150-200 mmHg), then is inflated a further 20 mmHg. The cuff is slowly released at a rate of 2-5mmHg per second. The first regular cyclical waveform is considered the toe systolic pressure.
Serum IL-1β levels at baseline and after the intervention	4 weeks	Analysis of serum interleukin-1β levels
Serum MCP-1 levels at baseline and after the intervention	4 weeks	Analysis of serum monocyte chemoattractant protein-1 (MCP-1) levels
Serum Met Hemoglobin levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum Hemoglobin (Hgb, Hb) levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum white blood cells (WBCs) levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum Erythrocyte Sedimentation Rate (ESR) levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum HIF-1α levels at baseline and after the intervention	4 weeks	Analysis of serum hypoxia-inducible factor 1-alpha (HIF-1α) levels
Serum Urea at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum Albumin (Alb) levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum ALT (alanine transaminase) levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum total Lymphocyte levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Neutrophils count at baseline and after the intervention	4 weeks	In a quantitative laboratory method
Serum C-Reactive Protein (CRP) levels at baseline and after the intervention	4 weeks	In a quantitative laboratory method

Trial Locations

Locations (1)

Mashhad University of Medical Sciences; 🇮🇷 Mashhad, Razavi Khorasan, Iran, Islamic Republic of