Effect of Photobiomodulation Treatment in Individuals With Multiple Sclerosis:

Study Overview
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Brief Summary
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Background: Multiple sclerosis (MS) is an autoimmune disease, for which the forms of treatment are medication and rehabilitation. However, in vitro and in vivo studies have demonstrated that photobiomodulation can be an effective treatment modality for inflammatory diseases, including MS. Photobiomodulation has a broad range of benefits, such as the avoidance of cell and tissue death, the stimulation of healing and injury repair, reductions in pain, edema and inflammation, cell proliferation and even apoptosis. The outcomes of photobiomodulation include the regeneration of cells, the stimulation of the growth of Schwann cells, a reduction in spasticity, functional improvements, a reduction in nitric oxide levels and the upregulation of the cytokine IL10, demonstrating that this therapeutic modality can offer neuro-protection. Methods: A randomized, controlled, double-blind, clinical trial is proposed. The patients will be divided into six groups. Groups 1 and 2 will receive sham and active photobiomodulation in the sublingual region, respectively. Groups 3 and 4 will receive sham and active photobiomodulation along the spinal cord, respectively. Group 5 will receive placebo treatment with photobiomodulation on the skin in the region of the radial artery with a specific bracelet. Group 6 will be treated with photobiomodulation on the skin in the region of the radial artery with a specific bracelet. Discussion: Treatment for MS is directed at the immune response and slowing the progression of the disease. This is one of the first clinical trials with sublingual and along the spinal cord photobiomodulation, which could help establish a new, promising treatment of the disease associated with pharmacological treatment.

Official Title
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Effect of Photobiomodulation Treatment in the Sublingual Region and Along the Spinal Column in Individuals With Multiple Sclerosis: Protocol for a Randomized, Controlled, Double-blind, Clinical Trial

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Radiation: Photobiomodulation in the sublingual region
* Radiation: Photobiomodulation in the spinal cord
* Radiation: Photobiomodulation in the radial artery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of MS; Age between 18 and 60 years; Currently undergoing pharmacological treatment; Capable of understanding and following verbal instructions; score of < 7 on the Expanded Disability Status Scale; No restriction will be imposed regarding gender. Exclusion Criteria: Other autoimmune diseases; Neoplasias; Heart failure; Respiratory failure; Renal insufficiency; Hepatic insufficiency; Acquired immunodeficiency syndrome; Patients with relapses of the disease will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham photobiomodulation in the sublingual region<br>A disposable plastic wrap will cover the application pen for the purposes of hygiene, and the laser will be placed for 10 minutes, without being turned on. | Radiation: Photobiomodulation in the sublingual region<br>* In the group submitted to sublingual irradiation, disposable plastic wrap will cover the application pen for the purposes of hygiene, and irradiation will take 10 minutes.<br>|
| Active Comparator: Photobiomodulation in the sublingual region<br>A disposable plastic wrap will cover the application pen for the purposes of hygiene, and the region will be irradiated for 10 minutes. | Radiation: Photobiomodulation in the sublingual region<br>* In the group submitted to sublingual irradiation, disposable plastic wrap will cover the application pen for the purposes of hygiene, and irradiation will take 10 minutes.<br>|
| Sham Comparator: Sham photobiomodulation along the spinal cord<br>Transcutaneous irradiation of the spinal cord will be pretended on segments corresponding to the nerve roots of the lumbosacral plexus (T12-S5) and cervicothoracic plexus (C5-T1-2). Twenty points will be wakely irradiated for 30 seconds (total treatment time: 10 minutes). | Radiation: Photobiomodulation in the spinal cord<br>* Transcutaneous irradiation of the spinal cord will be performed on segments corresponding to the nerve roots of the lumbosacral plexus (T12-S5) and cervicothoracic plexus (C5-T1-2). Twenty points will be irradiated for 30 seconds (total treatment time: 10 minutes).<br>|
| Active Comparator: Photobiomodulation along the spinal cord<br>Transcutaneous irradiation of the spinal cord will be performed on segments corresponding to the nerve roots of the lumbosacral plexus (T12-S5) and cervicothoracic plexus (C5-T1-2). Twenty points will be irradiated for 30 seconds (total treatment time: 10 minutes). | Radiation: Photobiomodulation in the spinal cord<br>* Transcutaneous irradiation of the spinal cord will be performed on segments corresponding to the nerve roots of the lumbosacral plexus (T12-S5) and cervicothoracic plexus (C5-T1-2). Twenty points will be irradiated for 30 seconds (total treatment time: 10 minutes).<br>|
| Sham Comparator: Sham Photobiomodulation in the radial artery<br>Intravascular laser irradiation will be applied to the skin in the region of the radial artery with a specific turned-off bracelet of the DMC laser Therapy EC model. | Radiation: Photobiomodulation in the radial artery<br>* Intravascular laser irradiation will be applied to the skin in the region of the radial artery with a specific bracelet of the DMC laser Therapy EC model.<br>|
| Active Comparator: Photobiomodulation in the radial artery<br>Intravascular laser irradiation will be applied to the skin in the region of the radial artery with a specific bracelet of the DMC laser Therapy EC model. | Radiation: Photobiomodulation in the radial artery<br>* Intravascular laser irradiation will be applied to the skin in the region of the radial artery with a specific bracelet of the DMC laser Therapy EC model.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative stress | The concentration of endogenous nitrite will be evaluated in serum samples using the Total Nitric Oxide and Nitrate/Nitrite Parameter Assay Kit (R&D) according to the manufacturer´s instructions. Briefly, 50 µL sample will be incubated in 96 well plates with the reaction diluent provided by the kit, Griess Reagent I and II for 10 min at room temperature. Reactions will be read at 540 nm. | Through study completion, about one year. | 
| Tumor Necrosis Factor Alpha | The quantification of the serum levels of IL-10 and TNFα will be performed using the Human IL-10 and THF-alpha ELISA MAX (Biolegend), according to the manufacturer's instructions. Briefly, plates will be coated with the capture anti-IL-10 or anti-TNF-alpha monoclonal antibody for 18h at 8°C, washed and then incubated with the reagent provided by the kit to block non-specific binding and to reduce background. Samples will be added to each well at room temperature for 2h and after wash, detection antibody solution will be added. Reactions will be revealed with the Avidin-HRP solution and the absorbance will be read at 450nm. | Through study completion, about one year. | 
| Interleukin-10 | The quantification of the serum levels of IL-10 and TNFα will be performed using the Human IL-10 and THF-alpha ELISA MAX (Biolegend), according to the manufacturer's instructions. Briefly, plates will be coated with the capture anti-IL-10 or anti-TNF-alpha monoclonal antibody for 18h at 8°C, washed and then incubated with the reagent provided by the kit to block non-specific binding and to reduce background. Samples will be added to each well at room temperature for 2h and after wash, detection antibody solution will be added. Reactions will be revealed with the Avidin-HRP solution and the absorbance will be read at 450nm. | Through study completion, about one year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EDSS | The participants will be evaluated before and after treatment using the Expanded Disability Status Scale administered by a physiotherapist. | Through study completion, about one year. |