Clinical trial NCT05850611: The Effect of Combination Therapy of Oral MB and PRP-FG in Patients With Non-healing Diabetic Foot Ulcer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Diabetic Foot Ulcers
Diabetic Wound
Keywords: Platelet-Rich Plasma-Fibrin Glue
DFU
Methylene blue
Non-healing Diabetic Foot Ulcers
Lead sponsor: Mashhad University of Medical Sciences
Sponsor class: OTHER
First posted: 2023-05-09
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The healing rate of the ulcer
timeFrame: 4 weeks
measure: Wound Size
timeFrame: 4 weeks
Secondary outcomes:
measure: TcPO2 at baseline and after the intervention
timeFrame: 4 weeks
measure: Oxygen saturation at baseline and after the intervention
timeFrame: 4 weeks
measure: Blood pressure (systolic and diastolic)
timeFrame: 4 weeks
measure: The resting systolic toe pressure (TP) at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum IL-1β levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum MCP-1 levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum TNF-α levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum IL-6 levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum HIF-1α levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum FBS levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum Insulin levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Lipid Profile at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum Urea at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum Creatinine at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum total bilirubin at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum Vitamin D levels at baseline and after the intervention
timeFrame: 4 weeks
measure: HbA1c at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum Albumin (Alb) levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Uric Acid levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum Homocysteine levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum ALT (alanine transaminase) levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum AST (Aspartate Transferase) levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum ALP (alkaline phosphatase) levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum Met Hemoglobin levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum Hemoglobin (Hgb, Hb) levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum white blood cells (WBCs) levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum total Lymphocyte levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Platelet count at baseline and after the intervention
timeFrame: 4 weeks
measure: Nitric oxide blood at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum lactate dehydrogenase (LDH) levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum Erythrocyte Sedimentation Rate (ESR) levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Serum C-Reactive Protein (CRP) levels at baseline and after the intervention
timeFrame: 4 weeks
measure: Neutrophils count at baseline and after the intervention
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Mashhad
country: Iran, Islamic Republic of
facility: Mashhad University of Medical Sciences
state: Razavi Khorasan
Study officials:
affiliation: Mashhad University of Medical Sciences, Mashhad, Iran
name: Daryoush Hamidi Alamdari, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: