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

Sponsor

Mashhad University of Medical Sciences (Other)

Overall Status

Recruiting

CT.gov ID

NCT05850611

Collaborator

(none)

Enrollment

Location

Arms

4.7

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Foot Ulcers Diabetic Wound	Drug: Methylene Blue Other: Milk (control) Drug: Methylene Blue and Platelet-Rich Plasma-Fibrin Glue Other: Milk and Platelet-Rich Plasma-Fibrin Glue (control)	Early Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Effect of Combination Therapy of Oral Methylene Blue and Platelet-rich Plasma-fibrin Glue in Patients With Non-healing Diabetic Foot Ulcer: a Pilot Study

Actual Study Start Date :

Apr 30, 2023

Anticipated Primary Completion Date :

Aug 21, 2023

Anticipated Study Completion Date :

Sep 21, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Methylene Blue The first intervention group includes diabetic patients with chronic foot ulcers who, despite common treatments, will be undergone oral methylene blue intervention for 4 weeks. Other Names: Methylthioninium chloride
Experimental: Milk (control) Patients with non-healing Diabetic Foot Ulcers only will receive 200 ml of milk for 4 weeks.	Other: Milk (control) Group B will receive 200 ml of milk for 4 weeks. Other Names: Placebo
Experimental: 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.	Drug: Methylene Blue and Platelet-Rich Plasma-Fibrin Glue Group C will be undergone synergistic 4-week treatment with oral methylene blue and fibrin glue. Other Names: Methylthioninium chloride and PRP-Fibrin Glue
Experimental: 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.	Other: Milk and Platelet-Rich Plasma-Fibrin Glue (control) Group D will be treated only with fibrin glue and 200 ml of milk for 4 weeks. Other Names: Placebo

Outcome Measures

Primary Outcome Measures

The healing rate of the ulcer [4 weeks]
Measurement of wound area with a ruler
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.

Secondary Outcome Measures

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 %)
Blood pressure (systolic and diastolic) [4 weeks]
The pressure of the blood in the circulatory system
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 TNF-α levels at baseline and after the intervention [4 weeks]
Analysis of serum tumor necrosis factor α (TNFα) levels
Serum IL-6 levels at baseline and after the intervention [4 weeks]
Analysis of serum interleukin-6 (IL-6) levels
Serum HIF-1α levels at baseline and after the intervention [4 weeks]
Analysis of serum hypoxia-inducible factor 1-alpha (HIF-1α) 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 Urea at baseline and after the intervention [4 weeks]
In a quantitative laboratory method
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
Serum Vitamin D levels at baseline and after the intervention [4 weeks]
In a quantitative laboratory method
HbA1c at baseline and after the intervention [4 weeks]
Glycated hemoglobin
Serum Albumin (Alb) levels at baseline and after the intervention [4 weeks]
In a quantitative laboratory method
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 ALT (alanine transaminase) 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
Serum ALP (alkaline phosphatase) levels at baseline and after the intervention [4 weeks]
In a quantitative laboratory method
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 total Lymphocyte levels at baseline and after the intervention [4 weeks]
In a quantitative laboratory method
Platelet count 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
Serum Erythrocyte Sedimentation Rate (ESR) levels 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
Neutrophils count at baseline and after the intervention [4 weeks]
In a quantitative laboratory method

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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