Back to resultsThe Effect of Combination Therapy of Oral MB and PRP-FG in Patients With Non-healing Diabetic Foot Ulcer
Primary Purpose
Diabetic Foot Ulcers, Diabetic Wound
Status
Recruiting
Phase
Early Phase 1
Locations
Iran, Islamic Republic of
Study Type
Interventional
Intervention
Methylene Blue
Milk (control)
Methylene Blue and Platelet-Rich Plasma-Fibrin Glue
Milk and Platelet-Rich Plasma-Fibrin Glue (control)
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Foot Ulcers focused on measuring Platelet-Rich Plasma-Fibrin Glue, DFU, Methylene blue, Non-healing Diabetic Foot Ulcers
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
Sites / Locations
- Mashhad University of Medical SciencesRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Methylene Blue
Milk (control)
Methylene Blue and Platelet-Rich Plasma-Fibrin Glue
Milk and Platelet-Rich Plasma-Fibrin Glue (control)
Arm Description
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.
Patients with non-healing Diabetic Foot Ulcers only will receive 200 ml of milk for 4 weeks.
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.
Patients with non-healing Diabetic Foot Ulcers will be treated with PRP-Fibrin-Glue and 200 ml of milk for 4 weeks.
Outcomes
Primary Outcome Measures
The healing rate of the ulcer
Measurement of wound area with a ruler
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.
Secondary Outcome Measures
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))
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 %)
Blood pressure (systolic and diastolic)
The pressure of the blood in the circulatory system
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.
Serum IL-1β levels at baseline and after the intervention
Analysis of serum interleukin-1β levels
Serum MCP-1 levels at baseline and after the intervention
Analysis of serum monocyte chemoattractant protein-1 (MCP-1) levels
Serum TNF-α levels at baseline and after the intervention
Analysis of serum tumor necrosis factor α (TNFα) levels
Serum IL-6 levels at baseline and after the intervention
Analysis of serum interleukin-6 (IL-6) levels
Serum HIF-1α levels at baseline and after the intervention
Analysis of serum hypoxia-inducible factor 1-alpha (HIF-1α) levels
Serum FBS levels at baseline and after the intervention
Analysis of serum fasting blood sugar (FBS ) levels
Serum Insulin levels at baseline and after the intervention
Analysis of Insulin levels
Lipid Profile at baseline and after the intervention
Serum Triglyceride, Cholesterol, HDL, LDL, VLDL
Serum Urea at baseline and after the intervention
In a quantitative laboratory method
Serum Creatinine at baseline and after the intervention
In a quantitative laboratory method
Serum total bilirubin at baseline and after the intervention
In a quantitative laboratory method
Serum Vitamin D levels at baseline and after the intervention
In a quantitative laboratory method
HbA1c at baseline and after the intervention
Glycated hemoglobin
Serum Albumin (Alb) levels at baseline and after the intervention
In a quantitative laboratory method
Uric Acid levels at baseline and after the intervention
In a quantitative laboratory method
Serum Homocysteine levels at baseline and after the intervention
In a quantitative laboratory method
Serum ALT (alanine transaminase) levels at baseline and after the intervention
In a quantitative laboratory method
Serum AST (Aspartate Transferase) levels at baseline and after the intervention
In a quantitative laboratory method
Serum ALP (alkaline phosphatase) levels at baseline and after the intervention
In a quantitative laboratory method
Serum Met Hemoglobin levels at baseline and after the intervention
In a quantitative laboratory method
Serum Hemoglobin (Hgb, Hb) levels at baseline and after the intervention
In a quantitative laboratory method
Serum white blood cells (WBCs) levels at baseline and after the intervention
In a quantitative laboratory method
Serum total Lymphocyte levels at baseline and after the intervention
In a quantitative laboratory method
Platelet count at baseline and after the intervention
In a quantitative laboratory method
Nitric oxide blood at baseline and after the intervention
In a quantitative laboratory method
Serum lactate dehydrogenase (LDH) levels at baseline and after the intervention
In a quantitative laboratory method
Serum Erythrocyte Sedimentation Rate (ESR) levels at baseline and after the intervention
In a quantitative laboratory method
Serum C-Reactive Protein (CRP) levels at baseline and after the intervention
In a quantitative laboratory method
Neutrophils count at baseline and after the intervention
In a quantitative laboratory method
Full Information
NCT ID
NCT05850611
First Posted
March 6, 2023
Last Updated
October 3, 2023
Sponsor
Mashhad University of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT05850611
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 30, 2023 (Actual)
Primary Completion Date
August 21, 2023 (Actual)
Study Completion Date
September 21, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mashhad University of Medical Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Foot Ulcers, Diabetic Wound
Keywords
Platelet-Rich Plasma-Fibrin Glue, DFU, Methylene blue, Non-healing Diabetic Foot Ulcers
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Factorial Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Methylene Blue
Arm Type
Experimental
Arm Description
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.
Arm Title
Milk (control)
Arm Type
Experimental
Arm Description
Patients with non-healing Diabetic Foot Ulcers only will receive 200 ml of milk for 4 weeks.
Arm Title
Methylene Blue and Platelet-Rich Plasma-Fibrin Glue
Arm Type
Experimental
Arm Description
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.
Arm Title
Milk and Platelet-Rich Plasma-Fibrin Glue (control)
Arm Type
Experimental
Arm Description
Patients with non-healing Diabetic Foot Ulcers will be treated with PRP-Fibrin-Glue and 200 ml of milk for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Methylene Blue
Other Intervention Name(s)
Methylthioninium chloride
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Milk (control)
Other Intervention Name(s)
Placebo
Intervention Description
Group B will receive 200 ml of milk for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Methylene Blue and Platelet-Rich Plasma-Fibrin Glue
Other Intervention Name(s)
Methylthioninium chloride and PRP-Fibrin Glue
Intervention Description
Group C will be undergone synergistic 4-week treatment with oral methylene blue and fibrin glue.
Intervention Type
Other
Intervention Name(s)
Milk and Platelet-Rich Plasma-Fibrin Glue (control)
Other Intervention Name(s)
Placebo
Intervention Description
Group D will be treated only with fibrin glue and 200 ml of milk for 4 weeks.
Primary Outcome Measure Information:
Title
The healing rate of the ulcer
Description
Measurement of wound area with a ruler
Time Frame
4 weeks
Title
Wound Size
Description
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.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
TcPO2 at baseline and after the intervention
Description
Transcutaneous oxygen tension (TcpO2) provides information about blood perfusion in the tissue immediately below the skin. (blood pressure, measured in millimeters of mercury (mmHg))
Time Frame
4 weeks
Title
Oxygen saturation at baseline and after the intervention
Description
Blood must contain a normal concentration of hemoglobin. that hemoglobin must be >95 % saturated with oxygen in arterial blood (sO2(a) >95 %)
Time Frame
4 weeks
Title
Blood pressure (systolic and diastolic)
Description
The pressure of the blood in the circulatory system
Time Frame
4 weeks
Title
The resting systolic toe pressure (TP) at baseline and after the intervention
Description
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.
Time Frame
4 weeks
Title
Serum IL-1β levels at baseline and after the intervention
Description
Analysis of serum interleukin-1β levels
Time Frame
4 weeks
Title
Serum MCP-1 levels at baseline and after the intervention
Description
Analysis of serum monocyte chemoattractant protein-1 (MCP-1) levels
Time Frame
4 weeks
Title
Serum TNF-α levels at baseline and after the intervention
Description
Analysis of serum tumor necrosis factor α (TNFα) levels
Time Frame
4 weeks
Title
Serum IL-6 levels at baseline and after the intervention
Description
Analysis of serum interleukin-6 (IL-6) levels
Time Frame
4 weeks
Title
Serum HIF-1α levels at baseline and after the intervention
Description
Analysis of serum hypoxia-inducible factor 1-alpha (HIF-1α) levels
Time Frame
4 weeks
Title
Serum FBS levels at baseline and after the intervention
Description
Analysis of serum fasting blood sugar (FBS ) levels
Time Frame
4 weeks
Title
Serum Insulin levels at baseline and after the intervention
Description
Analysis of Insulin levels
Time Frame
4 weeks
Title
Lipid Profile at baseline and after the intervention
Description
Serum Triglyceride, Cholesterol, HDL, LDL, VLDL
Time Frame
4 weeks
Title
Serum Urea at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum Creatinine at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum total bilirubin at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum Vitamin D levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
HbA1c at baseline and after the intervention
Description
Glycated hemoglobin
Time Frame
4 weeks
Title
Serum Albumin (Alb) levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Uric Acid levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum Homocysteine levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum ALT (alanine transaminase) levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum AST (Aspartate Transferase) levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum ALP (alkaline phosphatase) levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum Met Hemoglobin levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum Hemoglobin (Hgb, Hb) levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum white blood cells (WBCs) levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum total Lymphocyte levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Platelet count at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Nitric oxide blood at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum lactate dehydrogenase (LDH) levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum Erythrocyte Sedimentation Rate (ESR) levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Serum C-Reactive Protein (CRP) levels at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
Title
Neutrophils count at baseline and after the intervention
Description
In a quantitative laboratory method
Time Frame
4 weeks
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daryoush Hamidi Alamdari, Ph.D
Phone
+98 51 3882 8574
Email
hamidiad@mums.ac.ir
First Name & Middle Initial & Last Name or Official Title & Degree
Elaheh Emadi, Ph.D
Phone
+98 9355850931
Email
EmadiE4001@mums.ac.ir
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daryoush Hamidi Alamdari, Ph.D
Organizational Affiliation
Mashhad University of Medical Sciences, Mashhad, Iran
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mashhad University of Medical Sciences
City
Mashhad
State/Province
Razavi Khorasan
ZIP/Postal Code
99191-91778
Country
Iran, Islamic Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daryoush Hamidi Alamdari, Ph.D
Phone
98 51 3882 8574
Email
hamidiad@mums.ac.ir
First Name & Middle Initial & Last Name & Degree
Elaheh Emadi, Ph.D
Phone
98 9355850931
Email
EmadiE4001@mums.ac.ir
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All data related to the project after the unidentifiable people will be shared.
IPD Sharing Time Frame
Access to data is allowed 6 months after the publication of results.
IPD Sharing Access Criteria
The investigator's data will be available to university staff and academic institutions.
Learn more about this trial
The Effect of Combination Therapy of Oral MB and PRP-FG in Patients With Non-healing Diabetic Foot Ulcer
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