Clinical trial NCT03222544: Clinical Study of Methylene Blue - Mediated Photodynamic Therapy for Diabetic Lower Limb Ulcer
Official title: Efficacy and Safety of Methylene Blue -Mediated Photodynamic Therapy for Diabetic Lower Limb Ulcer : a Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetic Extremity Lower Ulcers
Keywords: methylene blue
Photodynamics Therapy
Lead sponsor: Chongqing Medical University
Sponsor class: OTHER
First posted: 2017-07-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline （Ulcer area）in the diabetic lower limb ulcer at day 7
timeFrame: Baseline and day 7
measure: Change from baseline (immediately before the first treatment) in the bacterial load of the ulcer at one hour (immediately after the first treatment)
timeFrame: Baseline and (immediately after the first treatment)，day 7,14,21,28
measure: Change from baseline(bacterial biofilm）
timeFrame: Baseline and day 7,14,21,28
Secondary outcomes:
measure: The dose of antibiotics
timeFrame: 7 days during treatment
measure: The time of antibiotics
timeFrame: 7 days during treatment
measure: Adverse events
timeFrame: 7 days during treatment
measure: A comparison of local NET neutrophil extracellular traps before the first treatment and after the tenth treatment
timeFrame: Baseline and day 7,14,21,28
measure: Inflammation control rate
timeFrame: 7 days during treatment
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: the First Affiliated Hospital, Chongqing Medical University, China
name: Qingfeng Cheng, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tardivo JP, Adami F, Correa JA, Pinhal MA, Baptista MS. A clinical trial testing the efficacy of PDT in preventing amputation in diabetic patients. Photodiagnosis Photodyn Ther. 2014 Sep;11(3):342-50. doi: 10.1016/j.pdpdt.2014.04.007. Epub 2014 May 9.
citation: Lei X, Liu B, Huang Z, Wu J. A clinical study of photodynamic therapy for chronic skin ulcers in lower limbs infected with Pseudomonas aeruginosa. Arch Dermatol Res. 2015 Jan;307(1):49-55. doi: 10.1007/s00403-014-1520-4. Epub 2014 Nov 20.
citation: Detty MR, Gibson SL, Wagner SJ. Current clinical and preclinical photosensitizers for use in photodynamic therapy. J Med Chem. 2004 Jul 29;47(16):3897-915. doi: 10.1021/jm040074b. No abstract available.
citation: Giraudeau C, Moussaron A, Stallivieri A, Mordon S, Frochot C. Indocyanine green: photosensitizer or chromophore? Still a debate. Curr Med Chem. 2014;21(16):1871-97. doi: 10.2174/0929867321666131218095802.
citation: Nicolau DP, Stein GE. Therapeutic options for diabetic foot infections: a review with an emphasis on tissue penetration characteristics. J Am Podiatr Med Assoc. 2010 Jan-Feb;100(1):52-63. doi: 10.7547/1000052.