Effect of Photobiomodulation as a Preventive Treatment for Diabetic Foot

Effect of Photobiomodulation as a Preventive Treatment for Diabetic Foot: Randomized Controlled Blinded Clinical Study

This study seeks to evaluate the effect of photobiomodulation (PBM) in the prevention of Diabetic foot (DF), in patients at moderate and high risk for its development, through a controlled, randomized, double-blind clinical trial. Individuals between 18 and 75 years old of both sexes, with type 2 diabetes mellitus (DM), and moderate and high risk for DF will be randomized and allocated into 2 groups of 32 participants each. The PBM Group will use a boot with 1344 LEDs, 504 of which are 660 nm located on the sides of the boot (28.5 milliwatt, 10 J per LED); 504 850 nm also located on the sides of the boot (23 milliwatt, 8 J per LED); 168 of 660 nm located at the base of the boot (28.5 milliwatt, 10 J per LED); 168 of 850 nm also located at the base of the boot (23 milliwatt, 8 J per LED) once a day for 6 minutes, for 60 days and will receive therapeutic education. Participants will be evaluated at baseline, after 30 days (clinical examination) and after 60 days (clinical examination, Peripheral Neuropathy (PN) assessment, Peripheral Artery Disease (PAD) assessment, blood and urine tests, and quality of life).

Study Overview

• Status: Recruiting
• Conditions: Diabetic Foot
• Intervention / Treatment: Device: Photobiomodulation; Behavioral: Therapeutic education; Device: Simulation of Photobiomodulation

Detailed Description

Diabetic foot (DF) prevention involves risk classification, systemic care, assessment of Peripheral Artery Disease (PAD) and Peripheral Neuropathy (PN), regular foot examination, therapeutic education, and routine use of appropriate footwear. Photobiomodulation (PBM) has been successfully applied in the healing of DF. In addition to the therapeutic effects of PBM, its preventive effects have attracted the attention of researchers. This study seeks to evaluate the effect of PBM in the prevention of DF, in patients at moderate and high risk for its development, through a controlled, randomized, double-blind clinical trial. Individuals between 18 and 75 years old of both sexes, with type 2 DM, and moderate and high risk for DF will be randomized and allocated into 2 groups of 32 participants each. The PBM Group will use a boot with 1344 LEDs, 504 of which are 660 nm located on the sides of the boot (28.5 milliwatt, 10 J per LED); 504 850 nm also located on the sides of the boot (23 milliwatt, 8 J per LED); 168 of 660 nm located at the base of the boot (28.5 milliwatt, 10 J per LED); 168 of 850 nm also located at the base of the boot (23 milliwatt, 8 J per LED) once a day for 6 minutes, for 60 days and will receive therapeutic education. Participants will be evaluated at baseline and after 30 days (clinical examination) and 60 days (clinical examination, PN assessment, PAD assessment, blood and urine tests, and quality of life). The collected data will be stored, and organized in a repository and the appropriate statistical tests will be applied for each specific analysis. In all tests, a significance level of 5% will be adopted.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kristianne KS Fernandes, PhD; Phone Number: +55 011 33859287; Email: kristianneporta@gmail.com
• Study Contact Backup: Name: Roselene Lourenço, PhD

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 02401-400
      • Recruiting
      • Conjunto Hospitalar do Mandaqui
      • Contact: Roselene Lourenço

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals diagnosed with type 2 Diabetes Mellitus (according to American Diabetes Association 2021 criteria),
• both sexes,
• between 18 and 75 years,
• Individuals classified, according to the International Working Group on the Diabetic Foot (IWGDF- 2019) scale, as moderate to high risk for developing diabetic foot,

Exclusion Criteria:

• Pregnant women
• Individuals diagnosed with type 1 diabetics,
• Individuals with neuropathy secondary to uncontrolled conditions (hypothyroidism, vitamin B12 deficiency, alcoholism),
• Individuals diagnosed with active infectious condition at the time of inclusion,
• Individuals diagnosed with active ulcer or infectious skin lesion on the legs/feet,
• Individuals with historic of osteomyelitis,
• Individuals with Parkinson's disease,
• Individuals with contracture condition,
• Individuals with severe lower limb ischemia (Fontaine III and IV - Rutherford 4 to 6),
• Individuals with a suspicious skin lesion for neoplasms or cutaneous dysplasias on the legs/feet
• Individuals diagnosed with oncologic disease or undergoing treatment within the last 3 (three) months,
• Individuals presenting unstable angina, recent acute myocardial infarction, history of severe arrhythmia within the last six months,
• Individuals diagnosed with decompensated Chronic Obstructive Pulmonary Disease (COPD),
• Inability to understand the ICF,
• Inability to attend appointments regularly.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Photobiomodulation Group; The PBM Group will use a boot with 1344 LEDs once daily for 6 minutes, over a period of 60 days, and will receive therapeutic education.	Device: Photobiomodulation; The PBM Group will use a boot with 1344 LEDs, including 504 LEDs of 660 nm located on the sides of the boot (28.5 mW, 10 J per LED); 504 LEDs of 850 nm also located on the sides of the boot (23 mW, 8 J per LED); 168 LEDs of 660 nm located at the base of the boot (28.5 mW, 10 J per LED); and 168 LEDs of 850 nm also located at the base of the boot (23 mW, 8 J per LED) once daily for 6 minutes, over 60 days.; Behavioral: Therapeutic education; Participants will receive therapeutic education regarding nutrition, foot examination, self-care, and guidance on physical activity.
Sham Comparator: Control Group; The Control Group will use a non-therapeutic LED boot (placebo) for 6 minutes once daily for 60 days and will also receive therapeutic education.	Behavioral: Therapeutic education; Participants will receive therapeutic education regarding nutrition, foot examination, self-care, and guidance on physical activity.; Device: Simulation of Photobiomodulation; The Control Group will use a non-therapeutic LED boot (sham procedure) for 6 minutes once daily for 60 days. The boot used is identical to the active boot, but there is no light emission.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ulcer Incidence	The incidence of foot ulcers will be assessed through clinical examination. In addition to these in-person assessments, participants will be monitored daily via telephone contact, during which the researchers (resident physicians) will inquire about any changes in the skin, discomfort, and the use of PBM equipment.	Baseline (Before the intervention)
Ulcer Incidence	The incidence of foot ulcers will be assessed through clinical examination. In addition to these in-person assessments, participants will be monitored daily via telephone contact, during which the researchers (resident physicians) will inquire about any changes in the skin, discomfort, and the use of PBM equipment.	at 30 days
Ulcer Incidence	The incidence of foot ulcers will be assessed through clinical examination. In addition to these in-person assessments, participants will be monitored daily via telephone contact, during which the researchers (resident physicians) will inquire about any changes in the skin, discomfort, and the use of PBM equipment.	at 60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tactile sensitivity with Semmes-Weinstein monofilament	This assessment will be conducted using the Semmes-Weinstein esthesiometer 5.07 with a 10 g filament, following the standard technique outlined in the IWGDF 2019 guidelines, as described in Annex 1. The test will be performed at three different locations on both feet. Protective sensation will be considered present if the patient responds correctly in two out of three applications at each location, and absent if they respond incorrectly in two out of three applications. Each esthesiometer will be used to evaluate a maximum of 10 participants on the same day and discarded after 70 evaluations to maintain accuracy.	Baseline (Before the intervention)
Tactile sensitivity with Semmes-Weinstein monofilament	This assessment will be conducted using the Semmes-Weinstein esthesiometer 5.07 with a 10 g filament, following the standard technique outlined in the IWGDF 2019 guidelines, as described in Annex 1. The test will be performed at three different locations on both feet. Protective sensation will be considered present if the patient responds correctly in two out of three applications at each location, and absent if they respond incorrectly in two out of three applications. Each esthesiometer will be used to evaluate a maximum of 10 participants on the same day and discarded after 70 evaluations to maintain accuracy.	at 60 days
Vibratory sensitivity	Participants will be tested with a 128 Hz tuning fork applied to the dorsal aspect of the distal phalanx of the first toe (hallux) or another toe if the hallux is absent. The test will be considered positive if the participant responds correctly to at least two out of three applications and negative if two out of three responses are incorrect	Baseline (Before the intervention)
Vibratory sensitivity	Participants will be tested with a 128 Hz tuning fork applied to the dorsal aspect of the distal phalanx of the first toe (hallux) or another toe if the hallux is absent. The test will be considered positive if the participant responds correctly to at least two out of three applications and negative if two out of three responses are incorrect	at 60 days
Assessment of Achilles reflex	The assessment of the Achilles reflex will be conducted with the participant seated, with the foot relaxed and suspended in slight dorsiflexion. A gentle tap will be applied with a reflex hammer to the Achilles tendon. The result will be considered abnormal if plantar flexion reflex of the foot is not observed. The loss of the Achilles tendon reflex is associated with diabetic neuropathy	Baseline (Before the intervention)
Assessment of Achilles reflex	The assessment of the Achilles reflex will be conducted with the participant seated, with the foot relaxed and suspended in slight dorsiflexion. A gentle tap will be applied with a reflex hammer to the Achilles tendon. The result will be considered abnormal if plantar flexion reflex of the foot is not observed. The loss of the Achilles tendon reflex is associated with diabetic neuropathy	at 60 days
Neuropathy Symptom Score (NSS)	For the calculation of ESN, patients will be asked about: the sensation of pain or discomfort in the legs and the occurrence, location, timing, and relief of symptoms such as fatigue, cramps, itching, burning, numbness, and tingling in the lower limb. PN will be considered mild when ESN scores between 3 and 4, moderate when between 5 and 6, or severe when reaching 7 to 9 points.	Baseline (Before the intervention)
Neuropathy Symptom Score (NSS)	For the calculation of ESN, patients will be asked about: the sensation of pain or discomfort in the legs and the occurrence, location, timing, and relief of symptoms such as fatigue, cramps, itching, burning, numbness, and tingling in the lower limbs. PN will be considered mild when ESN scores between 3 and 4, moderate when between 5 and 6, or severe when reaching 7 to 9 points.	at 60 days
Neuropathic Impairment Score (NIS)	Painful sensitivity will be assessed by applying pressure for 1 second with a blunt-tipped pin on the dorsal surface of the skin near the hallux nail, and thermal sensitivity will be assessed using a metal rod cooled to 32 and 36°C applied at the same location. Before the tests, procedures will be demonstrated on the hands. Sensitivities will be scored on each foot as present (0 points) or reduced/absent (1 point). The reflex will be scored as normal (0 points), present with effort (1 point), or absent (2 points). ECN ranges from 0 to 10, obtained by summing the scores of both feet. Values between 3 and 5 indicate mild neuropathy signs, between 6-8 indicate moderate neuropathy signs, and between 9 and 10 indicate severe neuropathy signs	Baseline (Before the intervention)
Neuropathic Impairment Score (NIS)	Painful sensitivity will be assessed by applying pressure for 1 second with a blunt-tipped pin on the dorsal surface of the skin near the hallux nail, and thermal sensitivity will be assessed using a metal rod cooled to 32 and 36°C applied at the same location. Before the tests, procedures will be demonstrated on the hands. Sensitivities will be scored on each foot as present (0 points) or reduced/absent (1 point). The reflex will be scored as normal (0 points), present with effort (1 point), or absent (2 points). ECN ranges from 0 to 10, obtained by summing the scores of both feet. Values between 3 and 5 indicate mild neuropathy signs, between 6-8 indicate moderate neuropathy signs, and between 9 and 10 indicate severe neuropathy signs	at 60 days
Evaluation of the degree of ischemia	The ankle-brachial index (ABI) will be measured by placing the sphygmomanometer cuff in the usual manner on the UL (above the elbow crease) and just above the ankle bones (ankle) on the LL with the patient in a supine position; inflating the cuff until the sound of blood flow becomes inaudible and then deflating it until the first sound of blood flow is heard, which corresponds to the maximum systolic pressure. Measurements will be repeated three times.	Baseline (Before the intervention)
Evaluation of the degree of ischemia	The ankle-brachial index (ABI) will be measured by placing the sphygmomanometer cuff in the usual manner on the UL (above the elbow crease) and just above the ankle bones (ankle) on the LL with the patient in a supine position; inflating the cuff until the sound of blood flow becomes inaudible and then deflating it until the first sound of blood flow is heard, which corresponds to the maximum systolic pressure. Measurements will be repeated three times.	at 60 days
Systolic peak velocity	In the distal segments of the anterior and posterior tibial arteries and fibular artery in cm²/s measured by Doppler ultrasound.	Baseline (Before the intervention)
Systolic peak velocity	In the distal segments of the anterior and posterior tibial arteries and fibular artery in cm²/s measured by Doppler ultrasound.	at 60 days
Resistance Index	In the distal segments of the anterior and posterior tibial arteries and fibular artery - calculated by the formula (systolic peak velocity - diastolic peak velocity) / systolic peak velocity.	Baseline (Before the intervention)
Resistance Index	In the distal segments of the anterior and posterior tibial arteries and fibular artery - calculated by the formula (systolic peak velocity - diastolic peak velocity) / systolic peak velocity.	at 60 days
Waveform pattern	The waveform pattern of the distal segments of the anterior and posterior tibial arteries and fibular artery in Doppler ultrasound examination will be classified as triphasic, biphasic, or monophasic.	Baseline (Before the intervention)
Waveform pattern	The waveform pattern of the distal segments of the anterior and posterior tibial arteries and fibular artery in Doppler ultrasound examination will be classified as triphasic, biphasic, or monophasic.	at 60 days
Evaluation of claudication	The accuracy of using the Edinburgh Claudication Questionnaire alone is debatable, but this instrument can be used as a complement to clinical evaluation data for PAD. The questionnaire consists of 6 questions and has been validated for Portuguese. The definition of positive claudication requires the following set of responses: 1 = "yes", 2 = "no", 3 = "yes", 5 = "usually disappears in 10 minutes or less", and 6 = "calf" and/or "thigh" and/or "buttock" (regardless of whether other locations are marked) or NEGATIVE if any different combination is marked. Question 4 is not used to define the presence but rather the severity of claudication: "No" = Grade 1 (mild severity); and "Yes" = Grade 2.	Baseline (Before the intervention)
Evaluation of claudication	The accuracy of using the Edinburgh Claudication Questionnaire alone is debatable, but this instrument can be used as a complement to clinical evaluation data for PAD. The questionnaire consists of 6 questions and has been validated for Portuguese. The definition of positive claudication requires the following set of responses: 1 = "yes", 2 = "no", 3 = "yes", 5 = "usually disappears in 10 minutes or less", and 6 = "calf" and/or "thigh" and/or "buttock" (regardless of whether other locations are marked) or NEGATIVE if any different combination is marked. Question 4 is not used to define the presence but rather the severity of claudication: "No" = Grade 1 (mild severity); and "Yes" = Grade 2.	at 60 days
Thermography	. To utilize this technique, the imaging room should be climate-controlled with a stabilized temperature between 21 and 23°C. After removing shoes and socks, participants will lie in a supine position with a pillow under their legs without ankle support, keeping their legs slightly apart for at least 15 minutes to allow temperature equilibrium and circulation stabilization of the limbs. Participants will be instructed to clean their lower limbs or take a bath at least 2 hours before the examination, avoid physical activity on the day of the examination, and refrain from applying creams or any substances to the lower limbs. Infrared images (thermograms) will be captured by a highly sensitive infrared sensor (18mm, resolution 320x240 pixels), Flir T420®, supported on a tripod maintained at 150 cm from the participants' foot soles, and a 15 cm ruler will be included in each image.	Baseline (Before the intervention)
Thermography	. To utilize this technique, the imaging room should be climate-controlled with a stabilized temperature between 21 and 23°C. After removing shoes and socks, participants will lie in a supine position with a pillow under their legs without ankle support, keeping their legs slightly apart for at least 15 minutes to allow temperature equilibrium and circulation stabilization of the limbs. Participants will be instructed to clean their lower limbs or take a bath at least 2 hours before the examination, avoid physical activity on the day of the examination, and refrain from applying creams or any substances to the lower limbs. Infrared images (thermograms) will be captured by a highly sensitive infrared sensor (18mm, resolution 320x240 pixels), Flir T420®, supported on a tripod maintained at 150 cm from the participants' foot soles, and a 15 cm ruler will be included in each image..	at 60 days
Quality of Life Assessment	The quality of life of individuals will be assessed using the Diabetes-21 instrument, which is a multidimensional scale adapted from the Diabetes-39, validated for Brazilian Portuguese.	Baseline (Before the intervention)
Quality of Life Assessment	The quality of life of individuals will be assessed using the Diabetes-21 instrument, which is a multidimensional scale adapted from the Diabetes-39, validated for Brazilian Portuguese.	at 60 days

Collaborators and Investigators

• Sponsor: University of Nove de Julho
• Investigators: Principal Investigator: Kristianne KS Fernandes, PhD, University of Nove de Julho

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: February 27, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: October 4, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: diabetes mellitus; therapeutic education; photobiomodulation; LED light
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Ulcer; Diabetic Foot
• Other Study ID Numbers: 5.888.210

Drug and device information, study documents

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