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

Not Applicable

• Conditions: Diabetic Extremity Lower Ulcers
• Interventions: Combination Product: Photon therapy instrument; Combination Product: methylene blue

• Registration Number: NCT03222544
• Lead Sponsor: Chongqing Medical University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-07-05
• Study First Submitted QC: 2017-07-17
• Study First Posted: 2017-07-19
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-22
• Last Update Posted: 2019-04-23
• Study Start: 2019-04-29
• Primary Completion: 2020-04-29
• Study Completion: 2020-06-29

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Photon therapy	Photon therapy instrument	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.
Photodynamic Therapy	methylene blue	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The First Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China