Clinical Study of Methylene Blue - Mediated Photodynamic Therapy for Diabetic Lower Limb Ulcer

Study Overview
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Brief Summary
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The investigators designed this prospective, randomized control study to confirm the efficacy and safety of methylene blue - mediated photodynamic therapy for diabetic lower limb ulcer and to explore its mechanism.

Detailed Description
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OBJECTIVE- Infection is associated with poor healing of diabetic lower limb ulcer. Diabetic lower limb ulcer are often lower extremity vascular stenosis or occlusion, poor blood supply, making local ulcer local antibacterial drugs difficult to effectively reach and distribution, resulting in systemic antibacterial efficacy is limited, and easy to induce bacterial resistance at the same time . In recent years, the incidence of clinical multidrug-resistant bacteria increased, increasing the difficulty and cost of treatment. The current study attempts to identify whether the photodynamic therapy (PDT) would kill the surface of ulcer bacteria and promote ulcer healing, and explore the mechanism of methylene blue-mediated photodynamic therapy for diabetic lower limb ulcer RESEARCH DESIGN AND METHODS-This study evaluated six clinical indicators： diabetic foot ulcer area reduction rate, inflammation control rate, Local bacterial load, the dose and use time of antibiotics, adverse reaction rate, bacterial biofilm,local neutrophil extracellular traps. The efficacy and safety of PDT could be confirmed if the clinical indicators of PDT group is better than the control group. In this study, three methods were used to investigate the mechanism of -methylene blue mediated photodynamic therapy for diabetic lower limb ulcer: a comparison of the bacterial load, bacterial biofilm,local neutrophil extracellular traps of the ulcer immediately pre-treatment and immediately,1-week ,2 week,1 momth post-treatment ; EXPECTED RESULTS-The investigators will expect that methylene blue-mediated photodynamic therapy could kill bacteria on the surface of diabetic lower limb ulcer and accelerate wound healing.

Official Title
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Efficacy and Safety of Methylene Blue -Mediated Photodynamic Therapy for Diabetic Lower Limb Ulcer : a Randomized Controlled Study

Conditions
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Diabetic Extremity Lower Ulcers

Intervention / Treatment
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* Combination Product: methylene blue
* Combination Product: Photon therapy instrument


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Understand the whole test process, voluntary and signed informed consent form. 2. Men and women aged 18 to 80 years old. 3. Diagnosed with diabetic lower limb ulcer. 4. Ulcer duration> 1 month of wagner grade Ⅱ, Ⅲ subjects. 5. An ulcer area ≤100 cm² or of linear dimension ≤ 10 cm. Exclusion Criteria: 1. Diagnosis of systemic infection or any concomitant infection that would require treatment with an additional antimicrobial agent. 2. Pregnant or lactating women. 3. Wagner grade Ⅰ, Ⅳ, Ⅴ subjects. 4. Patients with a peripheral vascular disease require immediate revascularization, and/or an ankle brachial systolic blood pressure (SBP) index<0.5 in the infected limb. 5. Patients with inappropriate health to participate as determined by the principal investigators. 6. Patients in the hepatitis A, hepatitis B, AIDS, tuberculosis and other infectious diseases of the active period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Photodynamic Therapy<br>The photosensitizer, methylene blue, is applied topically to the ulcer surface and the ulcer was shielded from light for 15 min. Then the ulcer area is illuminated using a photon therapy instrument for 20 minutes. Photodynamic therapy is applied once a day for a total of seven times. | Combination Product: methylene blue<br>* Continue treatment after 5mins suspension if the patient feels that the local temperature is too high to stand<br>|
| Active Comparator: Photon therapy<br>The placebo is applied topically to the ulcer surface and the ulcer was shielded from light for 15 min. Then the ulcer area is illuminated using a photon therapy instrument for 20 minutes. Photon therapy is applied once a day for a total of seven times. | Combination Product: Photon therapy instrument<br>* Continue treatment after 5mins suspension if the patient feels that the local temperature is too high to stand<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline （Ulcer area）in the diabetic lower limb ulcer at day 7 | Changes of ulcer area before and after treatment | Baseline and day 7 | 
| Change from baseline (immediately before the first treatment) in the bacterial load of the ulcer at one hour (immediately after the first treatment) | Changes of local bacterial load before and after treatment | Baseline and (immediately after the first treatment)，day 7,14,21,28 | 
| Change from baseline(bacterial biofilm） | Changes of local bacterial biofilm before and after treatment | Baseline and day 7,14,21,28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The dose of antibiotics | Dosage of antibiotics during treatment | 7 days during treatment | 
| The time of antibiotics | Antibiotic use time during treatment | 7 days during treatment | 
| Adverse events | including pain,redness, and swelling | 7 days during treatment | 
| A comparison of local NET neutrophil extracellular traps before the first treatment and after the tenth treatment | Fluorescence intensity and area of local NET | Baseline and day 7,14,21,28 | 
| Inflammation control rate | Duration of inflammation | 7 days during treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methylene blue, Photodynamics Therapy