Effects of Low Level Laser Therapy on Functional Capacity and DNA Damage of Patients With Chronic Kidney Failure

Study Overview
=================
Brief Summary
-----------------
This study aims to verify the effects of low level laser therapy (LLLT) on functional capacity, DNA damage, lower limbs muscle strength, quadriceps muscle architecture, muscle pain and perception of lower limb fatigue, inflammatory profile, oxidative stress and quality of life of patients with chronic kidney failure on hemodialysis. Patients will be randomized into two groups: the control group and the LLLT group. The control group will only be evaluated and reassessed. The LLLT group in addition to the evaluations will receive LLLT three times a week for eight weeks during HD. The evaluations will be performed pre-intervention, after 4 and 8 weeks of therapy. However, the muscle architecture evaluation will be performed only at pre intervention and after 8 weeks. The evaluations carried out are: six-minute walk test for functional capacity; alkaline comet assay for DNA damage; sit-and-lift test, and load cell dynamometry for evaluation of lower limbs muscle strength; quadriceps ultrasonography for muscle architecture and echogenicity; visual analogue scale for pain; subjective perception of effort by Borg scale for fatigue; measurement of interleukins 6 and 10, tumor necrosis factor, reative C protein and muscle damage markers (lactate, creatine kinase) for the inflammatory profile; protein carbonylation, superoxide dismutase, catalase, total sulfuric acid and dichlorofluorescein diacetate for oxidative stress and application of the Kidney Disease and Quality-of-Life-Short-Form and EQ-5D questionnaires for quality of life.

Detailed Description
-----------------
Chronic kidney disease (CKD) consists of kidney damage and progressive and irreversible loss of kidney function and in its later stage (terminal phase) is called chronic kidney failure (CKF). Although hemodialysis (HD) substitutes some of the lost renal functions, patients suffer from some changes that characterize uremic syndrome, such as peripheral motor neuropathy, osteomalacia, cardiac and musculoskeletal myopathies, anemia, among other alterations. This study aims to verify the effects of low level laser therapy (LLLT) on functional capacity, DNA damage, lower limbs muscle strength, quadriceps muscle architecture, muscle pain and perception of lower limb fatigue, inflammatory profile, oxidative stress and quality of life of patients with chronic kidney failure on hemodialysis. Patients will be randomized into two groups: the control group and the LLLT group. The control group will only be evaluated and reassessed. The LLLT group in addition to the evaluations will receive LLLT three times a week for eight weeks during HD. The evaluations will be performed pre-intervention, after 4 and 8 weeks of therapy. However, the muscle architecture evaluation will be performed only at pre intervention and after 8 weeks. The evaluations carried out are: a six-minute walk test for functional capacity; alkaline comet assay for DNA damage; sit-and-lift test, and load cell dynamometry for evaluation of lower limbs muscle strength; quadriceps ultrasonography for muscle architecture and echogenicity; visual analogue scale for pain; subjective perception of effort by Borg scale for fatigue; measurement of interleukins 6 and 10, tumor necrosis factor, reative C protein and muscle damage markers (lactate, creatine kinase) for the inflammatory profile; protein carbonylation, superoxide dismutase, catalase, total sulfuric acid and dichlorofluorescein diacetate for oxidative stress and application of the Kidney Disease and Quality-of-Life-Short-Form and EQ-5D questionnaires for quality of life. The expected results at the end of the protocol are: greater distance covered in the walking test; reduction of DNA damage, increase in lower limbs strength; maintenance of muscle mass; reduction of pain and fatigue levels as well as the inflammatory profile and levels of oxidative stress, as well as improvement in the quality of life for the group LLLT.

Official Title
-----------------
Effects of Low Level Laser Therapy on Functional Capacity and DNA Damage of Patients With Chronic Kidney Failure on Hemodialysis: Randomized Clinical Trial

Conditions
-----------------
Low-Level Light Therapy, Renal Insufficiency, Chronic, Renal Dialysis, Clinical Trial

Intervention / Treatment
-----------------
* Other: Low Level Laser Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with chronic kidney failure on hemodialysis for more than 3 months; Dialysis with weekly frequency of 3 times/week; Adequate urea clearance rate during hemodialysis (Kt/V ≥ 1.2 or URR ≥65%). Exclusion Criteria: Cognitive dysfunction Epidermal lesions at the site of laser application Patients with active carcinoma Patients with recent sequel of stroke (three months) Recent myocardium acute infarction (two months) Uncontrolled hypertension (SBP> 230 mmHg and DBP> 120 mmHg) Grade IV heart failure according to the New York Heart Association or decompensated Unstable angina Peripheral vascular changes in lower limbs such as deep venous thrombosis Disabling osteoarticular or musculoskeletal disease Uncontrolled diabetes (glycemia> 300mg/dL) Febrile condition and/or infectious disease Active smoking.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Level Laser Therapy group<br>Six points of application will be defined in the quadriceps and two points of application in the gastrocnemius. The parameters adopted for the irradiation will be: 30 Joules per application point, wavelength of 660 and 850 nm and output power of 200 mW. Each point will be radiated for 30 seconds. | Other: Low Level Laser Therapy<br>* For application of the LLLT in the quadriceps muscle the patient will be in dorsal decubitus, with the legs extended and will be defined by the palpation of the muscle belts six points of application: two points in the distal region of the vastus medialis muscle, two points of the distal region of the vastus lateral muscle and two points of the central region of the rectus femoris muscle. For the application of LLLT in the gastrocnemius muscle the patient will remain in the supine position, but will be oriented to keep the hips and knees flexed at 90º and 45º respectively. Two application points will be defined, one in the lateral ventricle and the other in the medial ventricle, but both in the distal region of the muscle.<br>* Other names: Low-Level Light Therapy;|
| No Intervention: Control group<br>This group will receive no intervention. This group will be evaluated before the intervention, after four and eight weeks of follow up. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Functional Capacity | Functional capacity will be assessed by the Six-Minute Walk Test | Before intervention, after 4 and 8 weeks | 
| Change in DNA Damage | DNA damage will be assessed by the alkaline comet assay | Before intervention, after 4 and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Muscle Strength of Lower Limbs | Muscle strength of lower limbs will be assessed by dynamometry | Before intervention, after 4 and 8 weeks | 
| Change in Muscle Architecture | Muscle architecture of quadriceps will be assessed by ultrasonography | Before intervention and after 8 weeks | 
| Change in Muscle Pain | Muscle pain will be assessed by analogic visual scale | Before intervention, after 4 and 8 weeks | 
| Change in Fatigue of Lower Limbs Fatigue of lower limbs | Fatigue of lower limbs will be assessed by Borg's subjective effort perception scale Fatigue of lower limbs will be assessed by Borg's effort perception scale | Before intervention, after 4 and 8 weeks | 
| Change in Oxidative Stress | Oxidative stress will be assessed by measurement of oxidative and antioxidant markers | Before intervention, after 4 and 8 weeks | 
| Change in Inflammatory Profile | Inflammatory profile will be assessed by measurement of interleukins and markers of muscle damage | Before intervention, after 4 and 8 weeks | 
| Change in Quality of Life | Quality of life will be assessed by Kidney Disease and Quality-of-Life Short-Form questionnaire | Before intervention and after 8 weeks | 
| Change in Quality of Life | Quality of life will be assessed by EQ-5D | Before intervention, after 4 and after 8 weeks |