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

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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetic Extremity Lower Ulcers
• Intervention / Treatment: Combination product: methylene blue; Combination product: Photon therapy instrument

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qingfeng Cheng, PhD; Phone Number: 086-23-89011510; Email: cqf19760516@163.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400016
      • Recruiting
      • The First Affiliated Hospital of Chongqing Medical University
      • Contact: Qingfeng Cheng, PhD; Phone Number: 086-23-89011510; Email: cqf19760516@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Photodynamic Therapy; 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; Continue treatment after 5mins suspension if the patient feels that the local temperature is too high to stand
Active Comparator: Photon therapy; 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; Continue treatment after 5mins suspension if the patient feels that the local temperature is too high to stand

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chongqing Medical University
• Investigators: Principal Investigator: Qingfeng Cheng, PhD, the First Affiliated Hospital, Chongqing Medical University, China

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 29, 2019
• Primary Completion (Anticipated): April 29, 2020
• Study Completion (Anticipated): June 29, 2020

Study Registration Dates

• First Submitted: July 5, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 19, 2017

Study Record Updates

• Last Update Posted (Actual): April 23, 2019
• Last Update Submitted That Met QC Criteria: April 22, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: methylene blue; Photodynamics Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Ulcer; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Methylene Blue
• Other Study ID Numbers: PDT2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No