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

October 3, 2023 updated by: Daryoush Hamidi Alamdari, PhD, Mashhad University of Medical Sciences

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Daryoush Hamidi Alamdari, Ph.D
  • Phone Number: +98 51 3882 8574
  • Email: hamidiad@mums.ac.ir

Study Contact Backup

Study Locations

  • Iran, Islamic Republic of
    • Razavi Khorasan
      • Mashhad, Razavi Khorasan, Iran, Islamic Republic of, 99191-91778
        • Recruiting
        • Mashhad University of Medical Sciences
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The healing rate of the ulcer
Time Frame: 4 weeks
Measurement of wound area with a ruler
4 weeks
Wound Size
Time Frame: 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.
4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
TcPO2 at baseline and after the intervention
Time Frame: 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))
4 weeks
Oxygen saturation at baseline and after the intervention
Time Frame: 4 weeks
Blood must contain a normal concentration of hemoglobin. that hemoglobin must be >95 % saturated with oxygen in arterial blood (sO2(a) >95 %)
4 weeks
Blood pressure (systolic and diastolic)
Time Frame: 4 weeks
The pressure of the blood in the circulatory system
4 weeks
The resting systolic toe pressure (TP) at baseline and after the intervention
Time Frame: 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.
4 weeks
Serum IL-1β levels at baseline and after the intervention
Time Frame: 4 weeks
Analysis of serum interleukin-1β levels
4 weeks
Serum MCP-1 levels at baseline and after the intervention
Time Frame: 4 weeks
Analysis of serum monocyte chemoattractant protein-1 (MCP-1) levels
4 weeks
Serum TNF-α levels at baseline and after the intervention
Time Frame: 4 weeks
Analysis of serum tumor necrosis factor α (TNFα) levels
4 weeks
Serum IL-6 levels at baseline and after the intervention
Time Frame: 4 weeks
Analysis of serum interleukin-6 (IL-6) levels
4 weeks
Serum HIF-1α levels at baseline and after the intervention
Time Frame: 4 weeks
Analysis of serum hypoxia-inducible factor 1-alpha (HIF-1α) levels
4 weeks
Serum FBS levels at baseline and after the intervention
Time Frame: 4 weeks
Analysis of serum fasting blood sugar (FBS ) levels
4 weeks
Serum Insulin levels at baseline and after the intervention
Time Frame: 4 weeks
Analysis of Insulin levels
4 weeks
Lipid Profile at baseline and after the intervention
Time Frame: 4 weeks
Serum Triglyceride, Cholesterol, HDL, LDL, VLDL
4 weeks
Serum Urea at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum Creatinine at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum total bilirubin at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum Vitamin D levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
HbA1c at baseline and after the intervention
Time Frame: 4 weeks
Glycated hemoglobin
4 weeks
Serum Albumin (Alb) levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Uric Acid levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum Homocysteine levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum ALT (alanine transaminase) levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum AST (Aspartate Transferase) levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum ALP (alkaline phosphatase) levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum Met Hemoglobin levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum Hemoglobin (Hgb, Hb) levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum white blood cells (WBCs) levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum total Lymphocyte levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Platelet count at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Nitric oxide blood at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum lactate dehydrogenase (LDH) levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum Erythrocyte Sedimentation Rate (ESR) levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Serum C-Reactive Protein (CRP) levels at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks
Neutrophils count at baseline and after the intervention
Time Frame: 4 weeks
In a quantitative laboratory method
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mashhad University of Medical Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Daryoush Hamidi Alamdari, Ph.D, Mashhad University of Medical Sciences, Mashhad, Iran

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 21, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 21, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 6, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 9, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 4, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 3, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRCT20191228045924N3

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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