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

Diabetic Foot Ulcers Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05850611
• Other study ID #: IRCT20191228045924N3
• Status: Recruiting
• Phase: Early Phase 1
• Start date: April 30, 2023
• Est. completion date: September 21, 2024

Study information

• Verified date: October 2023
• Source: Mashhad University of Medical Sciences
• Contact: Daryoush Hamidi Alamdari, Ph.D
• Phone: +98 51 3882 8574
• Email: hamidiad[@]mums.ac.ir
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 21, 2024
• Est. primary completion date: August 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Foot
• Diabetic Foot Ulcers
• Diabetic Wound
• Foot Ulcer
• Ulcer

Intervention

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:
• Milk (control)
Group B will receive 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:
• 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.

Locations

Country	Name	City	State
Iran, Islamic Republic of	Mashhad University of Medical Sciences	Mashhad	Razavi Khorasan

Sponsors (1)

Lead Sponsor	Collaborator
Mashhad University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The healing rate of the ulcer	Measurement of wound area with a ruler	4 weeks
Primary	Wound Size	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.	4 weeks
Secondary	TcPO2 at baseline and after the intervention	Transcutaneous oxygen tension (TcpO2) provides information about blood perfusion in the tissue immediately below the skin. (blood pressure, measured in millimeters of mercury (mmHg))	4 weeks
Secondary	Oxygen saturation at baseline and after the intervention	Blood must contain a normal concentration of hemoglobin. that hemoglobin must be >95 % saturated with oxygen in arterial blood (sO2(a) >95 %)	4 weeks
Secondary	Blood pressure (systolic and diastolic)	The pressure of the blood in the circulatory system	4 weeks
Secondary	The resting systolic toe pressure (TP) at baseline and after the intervention	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.	4 weeks
Secondary	Serum IL-1ß levels at baseline and after the intervention	Analysis of serum interleukin-1ß levels	4 weeks
Secondary	Serum MCP-1 levels at baseline and after the intervention	Analysis of serum monocyte chemoattractant protein-1 (MCP-1) levels	4 weeks
Secondary	Serum TNF-a levels at baseline and after the intervention	Analysis of serum tumor necrosis factor a (TNFa) levels	4 weeks
Secondary	Serum IL-6 levels at baseline and after the intervention	Analysis of serum interleukin-6 (IL-6) levels	4 weeks
Secondary	Serum HIF-1a levels at baseline and after the intervention	Analysis of serum hypoxia-inducible factor 1-alpha (HIF-1a) levels	4 weeks
Secondary	Serum FBS levels at baseline and after the intervention	Analysis of serum fasting blood sugar (FBS ) levels	4 weeks
Secondary	Serum Insulin levels at baseline and after the intervention	Analysis of Insulin levels	4 weeks
Secondary	Lipid Profile at baseline and after the intervention	Serum Triglyceride, Cholesterol, HDL, LDL, VLDL	4 weeks
Secondary	Serum Urea at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum Creatinine at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum total bilirubin at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum Vitamin D levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	HbA1c at baseline and after the intervention	Glycated hemoglobin	4 weeks
Secondary	Serum Albumin (Alb) levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Uric Acid levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum Homocysteine levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum ALT (alanine transaminase) levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum AST (Aspartate Transferase) levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum ALP (alkaline phosphatase) levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum Met Hemoglobin levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum Hemoglobin (Hgb, Hb) levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum white blood cells (WBCs) levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum total Lymphocyte levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Platelet count at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Nitric oxide blood at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum lactate dehydrogenase (LDH) levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum Erythrocyte Sedimentation Rate (ESR) levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Serum C-Reactive Protein (CRP) levels at baseline and after the intervention	In a quantitative laboratory method	4 weeks
Secondary	Neutrophils count at baseline and after the intervention	In a quantitative laboratory method	4 weeks