Evaluation of the Effects of Photobiomodulation Therapy Combined With Static Magnetic Field (PBMT-sMF) on Temporary Pain Relief in Patients With Lateral Epicondylitis
Phase: NA
Conditions: Lateral Epicondylitis
Sponsor: University of Nove de Julho

 
 
 
 
 
 
 
 
 
MR5® Prototype Device 
 
 
 
 
 
  
A multi-center, triple-blind, placebo-controlled,  
randomized evaluation of the effect of the MR5® Prototype 
Device for temporary adjunctive use to relieve pain 
associated with Lateral Epicondylitis. 
 
 
 
 
 
 
MULTI RADIANCE MEDICAL®   
 
 
 
Version 2.5 
 
July 18, 2019 

MR5® Prototype Device for temporary adjunctive use to relieve pain associated with Lateral 
Epicondylitis. 
 
Version 2.5 
 
July 18, 2019 
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Table of Contents 
STUDY INFORMATION .............................................................................................................4 
SPONSOR .............................................................................................................................................................. 4 
PRINCIPAL CLINICAL INVESTIGATORS AND TEST SITES ......................................................................................... 4 
ETHICS COMMITTEE ............................................................................................................................................. 4 
DEVICE: MULTI RADIANCE MEDICAL® MR5® PROTOTYPE DEVICE .................................4 
DEVICE DESCRIPTION & DETAILS .......................................................................................................................... 6 
STUDY DURATION ................................................................................................................................................. 8 
LABELING .............................................................................................................................................................. 8 
PROPOSED INDICATIONS FOR USE ....................................................................................................................... 8 
EXPECTED RESULTS ............................................................................................................................................... 8 
REGULATORY HISTORY..........................................................................................................9 
TECHNOLOGY, LITERATURE, BACKGROUND, THEORY OF MECHANISM OF 
OPERATION, PRODUCT OVERVIEW & SAFETY ................................................................ 10 
BACKGROUND: ................................................................................................................................................... 10 
LATERAL EPICONDYLITIS: ............................................................................................................................... 10 
THEORY OF MECHANISM OF OPERATION .......................................................................................................... 12 
General Therapeutic Effects and Mechanism of Operation of Low Level Lasers ........................................... 12 
PRODUCT OVERVIEW ......................................................................................................................................... 15 
SAFETY ................................................................................................................................................................ 16 
DEVICE SAFETY .................................................................................................................................................... 17 
RISK AND PREVENTION OF EYE INJURY .......................................................................................................... 17 
Figure 5: Laser Safety Industries PN: 100-40-245 .......................................................................................... 17 
DEVICE LABELING................................................................................................................................................ 18 
Symbol Explanation:....................................................................................................................................... 18 
OTHER POTENTIAL RISKS .................................................................................................................................... 19 
STUDY INDICATION: LATERAL EPICONDYLITIS .............................................................. 20 
STUDY DESIGN ...................................................................................................................... 23 
SUBJECT GROUPS................................................................................................................................................ 23 
Test procedure groups: .................................................................................................................................. 24 
SUBJECTS ............................................................................................................................................................ 24 
Recruitment  (THREE SITES) ........................................................................................................................... 24 
Flyer ................................................................................................................................................................ 24 
Newspaper Ad ................................................................................................................................................ 25 
RANDOMIZATION ............................................................................................................................................... 26 
TRIPLE BLIND DESIGN ......................................................................................................................................... 26 
STUDY PROCEDURE ............................................................................................................. 29 
PRIMARY OUTCOME MEASURE: ......................................................................................................................... 29 
DEGREE OF PAIN RATING: ................................................................................................................................... 29 
SECONDARY OUTCOMES .................................................................................................................................... 30 
Grip Strength Test ......................................................................................................................................... 30 
TNF-α Marker - Blood Collection ................................................................................................................... 30 
BACKGROUND/RATIONALE: EPICONDYLITIS - TNF-α.................................................................................... 31 
ADVERSE EVENTS EVALUATION .......................................................................................................................... 31 
PRE-PROCEDURE ACTIVITIES .............................................................................................................................. 32 

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STUDY QUALIFICATION ....................................................................................................................................... 32 
INCLUSION CRITERIA .......................................................................................................................................... 33 
EXCLUSION CRITERIA .......................................................................................................................................... 34 
SUBJECT GROUP RANDOMIZATION .................................................................................................................... 35 
INDIVIDUALIZED PAIN MANAGEMENT REGIMEN STABILIZATION PHASE: ......................................................... 35 
DETERMINATION AND RECORDING OF THE INDIVIDUALIZED PAIN MANAGEMENT REGIMEN ......................... 34 
IMPLEMENTATION AND COMMENCEMENT OF THE INDIVIDUALIZED PAIN MANAGEMENT REGIMEN ............ 35 
ESTABLISHMENT OF PROCEDURE ADMINISTRATION VISIT SCHEDULE .............................................................. 35 
INDIVIDUALIZED PAIN MANAGEMENT REGIMEN STABILIZATION PHASE MEASURES ....................................... 36 
PRE-PROCEDURE ASSESSMENT PHASE ......................................................................... 36 
CONTINUED STUDY ELIGIBILITY EVALUATION .................................................................................................... 36 
PRE-PROCEDURE MEASURES .............................................................................................................................. 36 
PRE-PROCEDURE VARIABLES .............................................................................................................................. 36 
PROCEDURE ADMINISTRATION PHASE ............................................................................ 36 
PROCEDURE ADMINISTRATION PROTOCOL ....................................................................................................... 36 
PROCEDURE ADMINISTRATION PHASE MEASURES ...................................................... 38 
POST-PROCEDURE ADMINISTRATION PHASE ................................................................ 39 
POST-PROCEDURE ADMINISTRATION PHASE EVALUATION POINTS AND MEASURES ....................................... 39 
ADVERSE EVENTS ................................................................................................................................................ 39 
PRIVACY AND CONFIDENTIALITY ........................................................................................................................ 39 
MONITORING OF THE CLINICAL STUDY .............................................................................................................. 40 
STATISTICAL ANALYSIS ...................................................................................................... 40 
PRIMARY EFFICACY OUTCOME MEASURE: ......................................................................................................... 40 
PRIMARY EFFICACY OUTCOME STATISTICAL EVALUATION METHODS ............................................................... 41 
SUPPORTIVE OUTCOME MEASURES................................................................................................................... 42 
SUPPORTIVE MEASURES STATISTICAL EVALUATION METHODS ........................................................................ 42 
STATISTICAL EVALUATION OF APPLICATION OF PAIN MANAGEMENT REGIMEN .............................................. 42 
BLINDING EFFICACY EVALUATION ...................................................................................................................... 43 
POOLABILITY EVALUATION ................................................................................................................................. 46 
SAFETY ANALYSES ............................................................................................................................................... 46 
INFORMED CONSENT ......................................................................................................................................... 43 
CASE REPORT FORMS ......................................................................................................................................... 46 
 
APPENDICES 
APPENDIX A: Supporting Research Abstracts 
APPENDIX B: MRM Research Abstracts 
APPENDIX C: Informed Consent Form 
APPENDIX D: Supplemental Forms 
APPENDIX E: Case Report Forms 
  
 
 
 
 
 

MR5® Prototype Device for temporary adjunctive use to relieve pain associated with Lateral 
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STUDY INFORMATION 
 
SPONSOR 
Multi Radiance Medical  
6521 Davis Industrial Parkway  
Solon, Ohio 44139 USA 
Contact: Douglas Johnson, ATC, EES, CLS 
Chief Science Officer, Clinical and Scientific Affairs 
Telephone: 440-542-0761  
Fax: 440-542-0765  
Email: info@multiradiance.com  
www.multiradiance.com  
 
PRINCIPAL CLINICAL INVESTIGATORS AND TEST SITES 
 
Principal Clinical Investigator: Ernesto Cesar Pinto Leal Junior, PhD, MSc, PT 
Nove de Julho University – UNINOVE, Sao Paulo, Brazil. 
Email: ernesto.leal.junior@gmail.com  
 
Three Test Sites: 
 
Test Site #1: Laboratory of Phototherapy and Innovative Technologies in Health 
Nove de Julho University 
Vergueiro St. 235/249 
Liberdade, São Paulo - SP 
Brazil, 01504-001 
Telephone: +55 11 3385 9134 
  
Test Site #2: Vila Maria Outpatient Clinic 
Nove de Julho University 
Guaranésia St. 425 
Vila Maria, São Paulo - SP  
Brazil, 02112-000. 
 
Test Site #3: Core Sport Physical Therapy 
Siqueira Campos Ave, 1240 
Sumaré, Caraguatatuba - SP 
Brazil, 11661-400 
 
. 
 
ETHICS COMMITTEE 
Research Ethics Committee of Nove de Julho University 
Rua Vergueiro nº 235/249 – 3º subsolo 
Liberdade 
São Paulo – SP, Brazil  01504-001 
Telephone: +55 11 3385 9197 
E-mail: comitedeetica@uninove.br  
Approval # 3.669.043 
 
 

MR5® Prototype Device for temporary adjunctive use to relieve pain associated with Lateral 
Epicondylitis. 
 
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MR5® Prototype Device for temporary adjunctive use to relieve pain associated with Lateral 
Epicondylitis. 
 
Version 2.5 
 
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DEVICE: MULTI RADIANCE MEDICAL® MR5® Prototype Device 
 
DEVICE DESCRIPTION & DETAILS 
The Multi Radiance Medical MR5 Prototype Device is being evaluated in this study for 
temporary adjunctive use to relieve pain associated with Lateral Epicondylitis. 
 
The MR5 Prototype Device is designed to provide pain relief and non-invasive treatment of 
diverse conditions. The device, which may be used in combination with pharmacological 
methodologies, operates in phototherapeutic modes providing simultaneous penetrative 
impact of coherent and incoherent light energy. These include infrared and visible red light 
and are delivered into biological tissues in combination with a surface impact provided by a 
static magnetic field.  Phototherapeutic treatment is carried out by placing the light emitting 
aperture directly over the affected area according to the study protocol.   
 
 
 
 
Figure 1:  MR5 Prototype Device 
 
 
 
 
 
 
 
 

MR5® Prototype Device for temporary adjunctive use to relieve pain associated with Lateral 
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MR4 Prototype Settings 
Wavelength 
905 
850 
660 
905, 850, and 660 
Total Power (Average, W) 
0.001375 
0.25 
0.2 
0.451375 
Number of Diodes 
1 
3 
3 
7 
Power per Diode (W) 
0.001375 
0.083333 
0.066667 
N/A 
Irradiance W/cm2 
0.000344 
0.062500 
0.050000 
0.112844 
Fluence J/cm2 
0.020625 
3.750000 
3.000000 
6.770625 
Time Duration (seconds) 
60 
Frequency of SPL (Hz) 
250 
 
 
 
Laser Peak Pulse 
Power (W) 
50 
Laser Pulse Duration (s) 
0.00000011 
Aperture area (cm2) 
4 
Laser average power (W) 
0.001375 
IR average power (W) 
0.25 
Red average power (W) 
0.2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 2: The Multi Radiance Medical MR5 Prototype Device Technical 
S
f

MR5® Prototype Device for temporary adjunctive use to relieve pain associated with Lateral 
Epicondylitis. 
 
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PURPOSE OF STUDY 
 
The purpose of this multi-center clinical study is to determine the effectiveness of the Multi 
Radiance Medical MR5 Prototype Device manufactured by Multi Radiance Medical (the 
Company), MR5® Prototype Device for temporary adjunctive use to relieve pain associated 
with Lateral Epicondylitis. 
 
STUDY DURATION 
The estimated total duration of the study is four to five months. 
 
LABELING 
Once the device has been cleared for market in the U.S., the device will be labeled as a 
prescription device, per 21 CFR § 801.109. 
 
PROPOSED INDICATIONS FOR USE 
The indication (claim) being sought through support of the results of this clinical study is: 
“The Multi Radiance Medical MR5 Prototype Device is indicated for temporary adjunctive use 
to relieve pain associated with Lateral Epicondylitis.”  It is intended that the results of this 
clinical study be used to support a DeNovo submission to FDA for clearance to market the 
device for the intended indication. 
 
EXPECTED RESULTS 
Following completion of the study procedure protocol with the Multi Radiance Medical MR5 
Prototype Device, it is anticipated that relative to baseline (pain at rest), significantly more 
subjects in the test group than in the placebo group will show a 30% or greater reduction in 
self-reported VAS rating in the Lateral Epicondylitis following completion of the three-week 
study procedure administration phase. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

MR5® Prototype Device for temporary adjunctive use to relieve pain associated with Lateral 
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REGULATORY HISTORY 
 
The MR4™ Multi Radiance Therapy and its various emitters and accessories have received 
the following 510(k) clearances from the United States Food and Drug Administration (FDA): 
 
1. K080102 
• Device Name: MR4™ Multi Radiance Therapy System, TQ Solo, TQ Solo Pro, and 
LS50 Accessory 
• Regulatory Class: Class II 
• Product Code: ILY, GEX 
• Clearance date: August 20, 2008 
• Indications for Use: All four devices are indicated for temporary relief of minor muscle 
and joint pain, arthritis and muscle spasm, relieving stiffness, promoting relaxation of 
muscle tissue, and to temporarily increase local blood circulation where heat is 
indicated. 
• Over-The-Counter (OTC) use 
 
 
 
 
2.  K171354 
• Device Name: MR4™ Laser 
• Regulatory Class: Class II 
• Product Code: NHN 
• Clearance date: January 13, 2018 
• Indications for Use: MR4 Laser is indicated for adjunctive use in providing temporary 
relief of minor chronic neck and shoulder pain of musculoskeletal origin. 
• Prescription use 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TECHNOLOGY, LITERATURE, BACKGROUND, THEORY OF MECHANISM OF 
OPERATION, PRODUCT OVERVIEW & SAFETY 
 
BACKGROUND: 
LATERAL EPICONDYLITIS:  
Upper extremity musculoskeletal disorders are common in the general population. These 
disorders may include diseases such as cervical disc disease, rotator cuff disease, lateral 
and medial epicondylitis, carpal tunnel syndrome, osteoarthritis, and other conditionsi. 
Studies report that these disorders have a negative impact on quality of lifeii,iii,iv since upper 
extremity pain can cause substantial disability, need for health care, and loss of work timev. 
Among the most common upper extremity disorders are lateral and medial epicondylitis, 
which have been reported to significantly affect the upper extremity function, causing losses 
in daily living activitiesvi,vii.  
 
Lateral epicondylitis (LE) is one of the most frequently encountered lesions affecting the 
upper extremity and is the most common cause of elbow pain in adults. It occurs on the 
lateral side of the elbow where the common extensors originate from the lateral 
epicondyleviii,ix,x. It is defined as an injury involving the wrist common extensor tendons, 
particularly the carpi radialis brevis and extensor digitorumxi. LE is a common term used to 
describe a group of symptoms, including pain and tenderness over the origin of extensor 
muscles of the wrist and fingers, and is also known as tennis elbow, as it is frequently seen 
in racquet sports playersxii,xiii,xiv,xv. This clinical condition has a significant impact on the 
healthcare industry and society in generalxvi,xvii.  
 
LE can be considered an overuse injury which occurs on the lateral side of the elbow in the 
extensor tendons with repetitive micro-traumaxviii,xix. It typically presents around the lateral 
epicondyle elicited by forced wrist extension, this is the result of the degenerative 
angiofibroblastic hyperplasia of wrist extensor tendons due to repeated micro-traumasxx,xxi. 
This condition is usually related to repetitive occupations or hobbiesxxii. Besides overuse and 
repetitive movements, other relevant risk factors include wrong training, misalignment, 
flexibility problem, age, poor circulation and muscle weakening or imbalancexxiii,xxiv. While the 
exact pathophysiology behind the condition is not yet clear, and despite the presence of 
inflammatory cells locally, there are arguments that LE can be regarded as a degenerative 
process caused by muscle overuse, with subsequent tendinosis, microtrauma and tear of the 
extensor carpi radialis brevis tendonxxv,xxvi. 
 
The prevalence rate of LE is more than 1% in the general population, with a slight 
predominance among femalesxxvii,xxviii. It is commonly seen in racquet sports players with a 
reported incidence of 9 ~ 35% and prevalence of 14 ~ 41% among tennis playersxxix. The 
disease mostly affects people between the ages of 35 – 50 years, who have a history of 
repetitive activities involving the upper limbs, and the dominant upper limb is much more 
often involvedxxx,xxxi,xxxii. The high prevalence of LE leads to a significant socioeconomic 
burdenxxxiii. Diagnosis is usually based on clinical history and physical examination, for a 
differential diagnosis, multiple exams can be used including simple radiography, 
ultrasonography, magnetic resonance imaging and electrodiagnosisxxxiv. 
 
The clinical presentation of LE involves a painful or burning sensation over the humeral 
insertion of the common extensor tendonsxxxv. This pain can be exacerbated by wrist 
extensor activation, passive wrist flexion combined with passive elbow extensionxxxvi, and 
palpation over the lateral epicondyle or the origin of the wrist extensor muscle groupsxxxvii. 
People affected by LE in the lateral epicondyle show increased pain and decreased 
functional abilities due to the weakening of the rotator cuff and the scapula muscular 

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systemsxxxviii. They will commonly present with a loss of grip strength and usually report pain 
during daily activities such as grasping objects, turning doorknobs and shaking handsxxxix,xl. 
In some cases, the recovery phase can take several months, potentially impacting the quality 
of life and sports performance of these individualsxli,xlii. 
 
Despite the high incidence of LE, optimal treatment has not been established, and, although 
treatments are usually non-surgical, such as oral medications, physiotherapy and 
corticosteroid injection, surgical decompression has been used to treat LExliii. The relatively 
large number of options currently available for LE treatment could be attributed to the scarce 
evidence available about the disease etiology and the lack of agreement about definitive 
treatment for the conditionxliv,xlv,xlvi.   
 
Medial epicondylitis (ME) of the elbow is less commonly encountered than the lateral disease 
but is also a common pathologyxlvii,xlviii,xlix. The relative incidence of ME is 9.8% to 20%l,li, and 
is often referred to as "golfer's elbow,” because in the golf swing significant tension is noted 
across the medial aspect of the elbowlii,liii. However other activities involving repetitive use 
have also been implicated, they include tennis, swimming, weightlifting and work-related 
activitiesliv. With the continuation of sport practice and active use of the elbow in the aging 
population, it has been diagnosed with increasing frequencylv.  
 
The underlying etiology of ME is described as an angiofibroblastic tendinosis in the origin of 
the common flexor-pronator, it has also been characterized as a micro-tearing in the origin of 
the flexor masslvi. It occurs due to repetitive forced wrist extension and forearm supination 
during activities involving wrist flexion and forearm pronation causing flexor-pronator tendon 
degeneration. The confluence of the flexor carpi radialis and pronator teres is frequently a 
common site of injurylvii. A staged process of pathologic change in the tendon can result in 
structural breakdown and irreparable fibrosis or calcificationlviii. 
 
Patients typically report persistent medial-sided elbow pain that is exacerbated by daily 
activities, it is usually present with flexion of the wrist and fingers and pronation of the 
forearmlix,lx. The ME is primarily a condition of the middle aged, most injuries are 
degenerative in nature, but in some cases an acute trauma may precipitate the symptoms. 
Once the acute symptomatology is alleviated, focus is turned to flexor-pronator mass 
rehabilitation and injury preventionlxi. 
 
Treatment of ME is initiated with nonsurgical modalities, this supportive care includes activity 
modification, physical therapy, oral medications and corticosteroid injectionslxii. Conservative 
treatment has been shown to relieve the pain, however this may depend on the stage of 
presentation. Surgical treatment via open techniques is typically reserved for patients with 
persistent symptoms, typically after at least six months of nonsurgical carelxiii. 
 
Considering the importance and high incidence of these musculoskeletal disorders, LE and 
ME, a variety of therapeutic modalities has been employed in order to alleviate pain and 
repair the tissue. Treatment options include therapeutic exercise, bracing, shock wave or 
ultrasound therapylxiv, but many of them lack sufficient evidence of beneficial effectslxv,lxvi. The 
corticosteroid injections are often used but with limited successlxvii. Photobiomodulation 
therapy (PBMT) has been shown to stimulate tendon healing, this suggests that therapy 
using laser or light-emitting diodes (LEDs) is efficacious for the symptoms associated with 
chronic epicondylitislxviii.  
 
The PBMT was first used to target soft tissue inflammation and injuries, its applications have 
expanded to a multitude of musculoskeletal injuries, including tendon injurieslxix. PBMT can 

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be performed using lasers or LEDs and is possible over a range of wavelengths, studies 
have demonstrated favorable results using PBMT on the tendon repair process, evidenced 
by improved quality of remodeling and decreased inflammationlxx,lxxi,lxxii,lxxiii.  
 
The PBMT is non-thermal, thus its effects are related to photochemical and photobiological 
effects within the tissue and not to heatlxxiv. It is non-invasive, therapeutically beneficial and 
promotes a wide range of biological effects including the enhancement of energy production, 
gene expression and cell death preventionlxxv. The major intracellular molecule absorbing 
photons is cytochrome c oxidase, an enzyme present in mitochondria, which can be 
stimulated by PBMTlxxvi. So the PBMT modulates biological processes of cells in the 
mitochondrial level increasing oxygen consumption and production of adenosine 
triphosphate (ATP)lxxvii. The PBMT also has the advantage of not having severe side effects. 
  
Favorable results of PBMT in the tendon repair process have already been demonstrated, it 
promotes the deposition of collagen fibers in the early and late stages and minimization of 
inflammatory cells in the lesion arealxxviii,lxxix. These beneficial outcomes of PBMT can be 
attributed to the modulatory effect of fibroblast metabolism and collagen deposition by matrix 
metaloproteinases, and activation or inhibition of inflammatory mediators. This also supports 
the indications that PBMT treated tendons have a higher turnover rate of collagen and higher 
mechanical integrity when compared to non-treated tendonslxxx.  
 
Epicondylitis (lateral or medial) has a significant impact on the health care system and 
society in generallxxxi. Therefore, investigating the mechanisms involved in tendon repair in 
order to encourage the development of novel therapies for epicondylitis treatment is very 
important. According to the favorable results of PBMT in tendons repair processes, this type 
of therapy can be used as a therapeutic tool for management in epicondylitis, therefore, more 
investigations are necessary to establish the ideal parameters. With this in mind, we believe 
that PBMT, in the appropriate parameters, can significantly decrease pain and improve 
quality of life of patients presenting epicondylitis diagnosis. 
 
THEORY OF MECHANISM OF OPERATION  
The scientific principle underlying laser physics was first developed by Albert Einstein in 
1916. The biological effects of low-level laser therapy (LLLT) have been studied globally for 
over forty years with no unwanted side effects noted.  
 
General Therapeutic Effects and Mechanism of Operation of Low Level Lasers 
 
“Low-energy photon irradiation by low level laser light lasers or LED arrays has been found 
to modulate various biological processes in cell culture and animal models. This mechanism 
of photobiomodulation by LLLT lasers or LED arrays at the cellular level has been ascribed 
to the activation of mitochondrial respiratory chain components, resulting in initiation of a 
signaling cascade that promotes cellular proliferation and cytoprotection.”  
Source: Proc Natl Acad Sci U S A. 2003 Mar18; 100(6): 3439-44. 2003 Mar 07. 
 
L.A.S.E.R. (Light Amplification by Stimulated Emission of Radiation) is a name for a type of 
intense radiation of the light spectrum. A laser is a beam of light in which high energies can 
be concentrated. Laser light has unique physical properties of coherence and 
monochromaticity that other types of light do not have. It is these physical properties that 
make laser light is so effective compared to other kinds of light in the field of pain reduction 
and healing. When applied to injuries and lesions, low level laser light has been shown to 
stimulate healing and reduce pain by accelerating the speed, quality and strength of tissue 
repair and the reduction of inflammation. Laser therapy has been found to be particularly 

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effective over other standard therapies in relieving pain and other symptoms associated with 
chronic problems and injuries as it impacts the complete system of targeted muscles, 
tendons, ligaments, connective tissue, bone, nerve, and dermal tissues. 
 
The effects of low-level laser treatments are photochemical. Photons enter the tissue and are 
absorbed in the cell’s mitochondria and at the cell membrane by chromophores. These 
chromophores are photosensitizers that generate reactive oxygen species following 
irradiation thereby influencing cellular redox states and the mitochondrial respiratory chain. 
Within the mitochondria, the photonic energy is converted to electromagnetic energy in the 
form of molecular bonds in ATP (Adenosine Triphosphate). In order to interact with the living 
cell, laser light has to be absorbed by intracellular chromophores. Cell membrane 
permeability increases, which causes physiological changes to occur. These physiological 
changes affect macrophages, fibroblasts, endothelial cells, mast cells, and bradykinin and 
nerve conduction rates. The clinical and physiological effects are obtained by the way in 
which tissues absorb laser radiation. This tissue absorption depends on the wavelength of 
the beam itself and the power to ensure that the laser energy reaches the target tissue at the 
necessary clinical levels. The improper wavelength of laser light would not penetrate into the 
tissue to reach the target area. Furthermore, even if one has a laser with the proper 
wavelength, if the device does not have enough power to drive the energy into the tissue, the 
target area may not realize the potential benefits. Each type of laser emits light at a very 
specific wavelength which interacts with the irradiated tissue. It also acts in particular with the 
chromophores present in the tissue, but in a different way. A chromophore, intrinsic or 
extrinsic, is any substance, colored or clear, which is able to absorb radiation. Among the 
endogenous chromophores are water and hemoglobin, nucleic acid and proteins. Among the 
exogenic chromophores are porphyrins and hematoporphyrins, which are injected into the 
organism. These are described as photosensitizers because they fix themselves to the tissue 
making it photosensitive at specific wavelengths. 
 
The level of tissue penetration by the laser beam depends on the beam’s optical 
characteristics, as well as on the concentration and depth of the chromophores, which are 
absorbed at different percentages according to the laser light’s wavelength. For instance, 
water absorbs almost 100 percent of the laser irradiation at 10,600 nanometers, the 
wavelength of a CO2 gas laser. That is the reason why this type of laser wavelength is used 
in surgical applications. Other factors affecting the depth of penetration are the technical 
design of the laser device and the particular treatment technique used. There is no exact limit 
with respect to the depth penetrated by the light. The laser light gets weaker the further from 
the surface it penetrates where eventually the light intensity is so low that no biological effect 
from it can be measured. In addition to the factors mentioned, the depth of penetration is also 
contingent on tissue type, pigmentation and foreign substances on the skin surface such as 
creams or applied oils. Bone, muscles and other soft tissues are transparent to certain laser 
lights, which means that light can safely penetrate these tissues. The radiation in the visible 
spectrum, between 400 and 600 nanometers, is absorbed by the melanin, while the whole 
extension of the visible which goes from 420 to 750 nanometers is absorbed by composite 
tetrapyrrolics. In the infrared, which covers about 10,000 nanometers of light spectrum, water 
is the main chromophore. Fortunately, there exists a narrow band in the light spectrum where 
water is not a highly efficient chromophore, thereby allowing light energy to penetrate tissue 
that is rich in water content. This narrow band, which extends approximately from 600 to 
1,200 nanometers, is the so-called “therapeutic window” and is the range within which the 
output design of the Multi Radiance Medical® MR5® Prototype Device is based.  
 
In general, laser diodes are either continuous wave or pulsed. Continuous wave (CW) diodes 
emit laser energy continuously while pulsed diodes emit a radiation impulse with a high 

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amplitude (intensity) and duration which is typically extremely short: 100-200 nanoseconds. 
Continuous wave lasers produce a fixed level of power during emission. Although lacking the 
high peak power of a "true" or "super" pulsed laser, most continuous wave lasers can be 
made to flash a number of times per second to simulate pulse-like rhythms by interrupting 
the flow of light rapidly as in turning a light switch “off” and “on”. “True” or “super” pulsed 
lasers produce a brief high-power level light impulse. It is the high-power level achieved 
during each pulse that drives the light energy to the target tissue. Even though the pulse 
peaks at a high-power level there are no deleterious thermal effects in the tissue because the 
pulses are of such short duration. Therefore, the peak power of a “true” or “super” pulsed 
laser is quite high compared to its average pulse power. As such, “true” or “super” pulsed 
lasers are able to more effectively drive light energy into tissue.  
 
Therefore, in summary, LLLT: 
•  
Promotes healing in many conditions because it penetrates the skin, increases the 
 
ATP and activates enzymes in the targeted cells.  
•  
Cultivates a growth factor response within the cells and tissue as a result of increased 
 
ATP and protein synthesis.  
•  
Improves cell proliferation.  
•  
Provides pain relief as a result of increased endorphin release.  
•  
Strengthens the immune system response via increasing levels of lymphocyte 
 
activity.  
 
Additionally, low level laser light energy will only be absorbed by cells and tissues that are 
not functioning normally (impaired) and will have no effect on healthy cells. 
 
The process by which low level laser light aids in the production of ATP, thereby providing 
cells with more energy which in turn means the cells are in optimum condition to play their 
part in a natural healing process, works as follows: 
 
The effects of low-level laser light are photo-chemical (not thermal), 
triggering normal cellular function. 
 
PHOTONS 
 
 
ABSORBED IN CYTOCHROMES & PORPHYRINS  
WITHIN THE MITOCHONDRIA  
AND AT THE CELL MEMBRANE 
 
 
 
SINGLET OXYGEN PRODUCTON 
 
 
 
FORMATION OF PROTOC GRADIENTS ACROSS CELL MEMBRANE  
AND ACROSS MEMBRANE OF MITOCHODRIA 
 
 
  
  CHANGES IN         INCREASED                 DNA 
                                    CELL MEMBRANE     ATP LEVELS           PRODUCTION 
                                        PERMEABILITY 
 
 
PHYSIOLOGICAL CHANGES 
 
 
 

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Considering the general mechanism of operation of LLLT as explained above, it follows that 
LLLT provides relief from the Lateral Epicondyle by: 
▪ 
penetrating the skin of the Lateral Epicondyle region to increase the production of 
ATP and activate enzymes in the underlying targeted cells of the tissue to promote 
healing of the micro-tears in the tissue 
▪ 
cultivating a growth factor response within the cells and tissue as a result of the 
increased ATP production to promote new, healthier cell and tissue growth to 
strengthen and support tendons and musculature, to restore strength and flexibility 
and to protect against further damage 
▪ 
the anti-inflammatory properties of low-level lasers reduce the inflammation to 
provide pain relief.  
See Appendix A for Supporting Research Abstracts 
 
PRODUCT OVERVIEW 
Like other therapeutic laser and light-emitting commercially available devices.  The MR5™ 
emits visible and infrared photons that are absorbed by skin and tissue via cellular 
mitochondria which contain chromophores capable of absorbing light energy.  This creates a 
cellular cascade of events that result in an increase in ATP production which allows the cells 
to function more normally and to resolve or minimize the results of specific diseased states. 
  
The Multi Radiance® Medical devices combine a combination of wavelengths and light 
sources comprised of Super Pulsed Lasers (GaAs 905 nm), infrared and red LEDs (850 nm 
and 660 nm) wavelengths.  Albuquerque-Pontes et allxxxii investigated the effects of 
phototherapy with the combination of different light sources to establish if an optimal dose or 
wavelength was needed to stimulate the enhancement of ATP production.  Three different 
low-level laser therapy (LLLT) wavelengths (660, 875 and 905 nm) were used to analyze 
cytochrome c-oxidase (CCO), an enzyme in muscle, brain, and other tissues that catalyzes 
the transfer of a phosphate group from ATP to creatine, producing adenosine diphosphate 
(ADP) and phosphocreatine (PCr) expression by immunohistochemistry.  The results 
demonstrated that LLLT increased (p<0.05) CCO expression mainly with the following 
wavelengths and doses: 660nm with 1 J, 875nm with 3 J and 905nm with 1 J at each time-
point. These specific wavelengths and light sources were selective to optimize the biological 
effects of the entire phototherapeutic window, provide a greater depth of penetration and 
eliminate the thermal barrier. 
 
It has been suggested in the literature that other modes, such as super pulsing, may have 
different skin penetration time profiles.  Brondon, et allxxxiii found the super pulsing the laser 
allows for better penetration through melanin filters, indicating that pulsing may be beneficial 
in reaching deep target tissue in dark-skinned patients.  Joensen et allxxxiv evaluated a super 
pulsed 904nm LLLT and found the light energy penetrated 2-3 easier through the rat skin 
barrier than 810nm continuous.  There was an interesting linear increase in penetrating 
energy from 38% (SEM±1.4) to 58% (SEM±3.5) during 150 seconds of exposure during the 
study.  Therefore, the greatest depth of penetration occurs at the 904/905nm wavelengths 
and that the absorption occurs not just at the superficial layers of the skin, but in deeper 
layers as well. 
 
Leal-Junior and Albuquerque-Pontes evaluated the depth of penetration time profile (DPTP) 
of the original ACTIV and Albuquerque-Pontes, et al. performed the same study with the 
ACTIV PRO to determine the effects of concurrent multiple wavelengths of 660nm Red LED, 
875nm IRED and 905nm SPL. Each individual wavelength was tested separately with and 
without the tissue skin flaps to establish the percentage of energy penetration.  Data 
observed also confirmed what Joenson, et al found regarding the pattern of linearly 

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increasing penetration of the light over time by the super-pulsed laser.  The individual 
wavelength penetration profiles provided a predicted measurement (summated total of each 
individual wavelength) to compare with an actual reading of the combined wavelength time 
profile. 
 
The data suggests and demonstrates a pattern of linearly increasing penetration of the light 
over time with the device and 49% penetrating beyond the skin.  This skin penetration time 
profile allows for a greater proportion of the available light energy to penetrate beneath the 
skin.  By improving the efficiency of penetration, the necessary energy provided at the 
surface is significantly less, reduces the conversion into heat and avoids a dangerous rise in 
tissue temperature. 
See Appendix B for supporting research studies on Multi Radiance® Medical Technology 
 
SAFETY 
After 50+ years of low intensity level light applications in humans with lasers (or any other 
optical to near infrared light sources) there are no known reports of any adverse side effects 
to the best of our knowledge.lxxxv  The MR4™ Laser Therapy System and many other light 
devices are cleared (FDA, Health Canada, TGA) and considered safe for both professional 
and consumer home use (OTC).  Low level laser devices have been designated by FDA as 
non-significant risk.  Multi Radiance® Medical also complies with ISO 13485 Certification to 
ensure good manufacturing practices for consistency in product quality, monitoring and 
reporting.   
 
The Multi Radiance Medical Super Pulsed Infrared Laser (905 nm) in the ACTIV PRO 
creates the desired higher peak power, however due to the ultrashort pulses, there is little 
resulting heat accumulating within the target tissue.  Vanin, et al.lxxxvi replicated a study by 
Grandinétti, et al.lxxxvii that evaluated the thermal impact of the MR5 Prototype Device on light, 
medium and dark skin. Baseline measurements were taken prior to the start and skin 
temperatures were measured using a FLIR thermographic camera.  Four doses were 
applied: placebo, 25 J, 80 J, and 133 J to the skin.  The MR5 Prototype Device was set to full 
power (500 mW and 50 Hz frequency). 
 
Light 
Intermediate 
Dark 
Baseline 
33.84 
34.74 
34.48 
72 sec 
34.28 
34.86 
34.90 
228 sec 
34.54 
35.45 
35.21 
380 sec 
35.54 
36.46 
36.06 
 
There was a non-significant increase (p>0.05) in temperature (degrees C) for all skin types 
and with all doses.  No groups experienced excessive photothermal effects that may affect 
patient safety and no threat or concern regarding cytotoxicity in clinical practice exists. The 
lack of accumulating skin temperature may be attributed to the ultra-short pulse structure 
related to the frequency of the super pulsed laser and pulsing of the LEDs and IREDs. 

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DEVICE SAFETY 
RISK AND PREVENTION OF EYE INJURY 
The MR5 Prototype Device - This product is classified as Class 1 according to EN IEC 
60825-1:2007. Access to laser radiation in excess of Class 1 is not possible during normal 
operation, and/or maintenance functions. 
 
The MR5 Prototype Device is a Class 1 laser device, and as such, protective eye wear is not 
required. However, for comfort and added caution, Laser Safety Industries shade/tint level 3 
goggles that block out the spectrum of light from 600 nm to 950 nm will be provided to the 
subject and the treating investigator in this clinical study, as follows: 
 
The Laser Safety Industries PN: 100-40-245 light blue laser safety glasses, having the 
following OD specifications and shown in Figure 6 to the right. 
                                                 
                                               
▪ 
OD 2+ @ 630-650 nm 
▪ 
OD 3+ @ 650-690 nm 
▪ 
OD 6+ @ 690-1330 nm           
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 3: Laser Safety Industries PN: 100-40-245  
 
 
 

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DEVICE LABELING 
 
 
 
 
 
 
1. Manufacturer 
 
2. Type BF applied part 
 
3. Attention: see instructions for use 
 
4. Catalog number 
 
5. Serial number 
 
6. Lot number 
 
7. Manufacture date 
 
 
 
Symbol Explanation: 
 
 
 
 
 
 
 
 
 

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OTHER POTENTIAL RISKS 
 
Other potential risks and their mitigation include: 
 
 
 
 

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STUDY INDICATION: LATERAL EPICONDYLITIS 
  
Definition 
Lateral epicondylitis is the most common overuse syndrome in the elbow. It is an injury 
involving the extensor muscles of the forearm. These muscles originate on the lateral 
epicondylar region of the distal humerus. In a lot of cases, the insertion of the extensor carpi 
radialis brevis is involved. 
  
Statistics 
The right elbow was affected in 63% of cases; the left in 25%, with 12% of patients 
diagnosed with LET in both elbows. The highest incidence occurred in individuals aged 40 to 
49, with a 7.8 per 1,000 rate in men and a 10.2 per 1,000 rate in women. Most patients 
received bracing and NSAIDS as primary treatmentlxxxviii. 
  
Anatomy of the lateral elbow 
The elbow joint is made up of three bones: the humerus (upper arm bone), the radius and 
ulna (two bones in the forearm). At the distal end of the humerus there are two epicondyles, 
one lateral (on the outside) and one medial (on the inside). The area of maximal tenderness 
is usually an area just distal to the origin of the extensor muscles of the forearm at the lateral 
epicondyle. Most commonly, the extensor carpi radialis brevis (ECRB) is involved, but others 
may include the extensor digitorum, extensor carpi radialis longus (ECRL), and extensor 
carpi ulnaris. The radial nerve is also in close proximity to this region and divides into the 
superficial radial nerve and the posterior interosseous nerve.  
  
Etiologies of Lateral epicondylitis 
Lateral epicondylitis is classified as an overuse injury that may result in hyaline degeneration 
of the origin of the extensor tendon. Overuse of the muscles and tendons of the forearm and 
elbow together with repetitive contractions or manual tasks can put too much strain on the 
elbow tendons. These contractions or manual tasks require manipulation of the hand that 
causes maladaptation in tendon structure that lead to pain over the lateral epicondyle. 
Mostly, the pain is located anterior and distal from the lateral epicondyle. 
 
Epicondylitis occurs at least five times more often and predominantly occurs on the lateral 
rather than on the medial aspect of the joint, with a 4:1 to 7:1 ratio. It affects 1-3% of the 
population, with those 35-50 years old most commonly being affected. If a patient is <35 , it is 
important to consider differential diagnosis (growth plate disorder, referral from the cervical 
spine. If a patient is >50, consider OA, referred cervical spine pain. 
 
This injury is often work-related, any activity involving wrist extension, pronation or supination 
during manual labor, housework and hobbies are considered as important causal factors. 
Lateral epicondylitis is equally common in both sexes. Between the ages of 30-50 years the 
disease is most prevalent. Obtaining of the condition at the both lateral epicondyle is rare, 
the dominant arm has the greatest chance of the occurrence of lateral epicondylitis. Twenty 
percent of cases persist for more than a year. 
 
A systematic review identified 3 risk factors: handling tools heavier than 1 kg, handling loads 
heavier than 20 kg at least 10 times per day, and repetitive movements for more than 2 
hours per day. Other risk factors are overuse, repetitive movements, training errors, 
misalignments, flexibility problems, aging, poor circulation, strength deficits or muscle 
imbalance and psychological factorslxxxix. 
  
 
 

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There are several opinions concerning the cause of lateral epicondylitis: 
1. Inflammation 
a. Although the term epicondylitis implies the presence of an inflammatory 
condition, inflammation is present only in the earliest stages of the disease 
processxc.  
 
2. Microscopic tearing 
a. Nirschl and Pettrone attributed the cause to microscopic tearing with formation 
of reparative tissue (angiofibroblastic hyperplasia) in the origin of the extensor 
carpi radialis brevis (ECRB) muscle. This micro-tearing and repair response 
can lead to macroscopic tearing and structural failure of the origin of the 
ECRB muscle. 
b. Histology of tissue samples shows "collagen disorientation, disorganization, 
and fibre separation by increased proteoglycan content, increased cellularity, 
neovascularization, with local necrosis." Nirschl termed these histological 
findings bangiofibroblastic hyperplasia. The term has since been modified to 
bangiofibroblastic tendinosis. He noted that the tissue was characterized by 
disorganized, immature collagen formation with immature fibroblastic and 
vascular elements. This grey, friable tissue is found in association with varying 
degrees of tearing involving the extensor carpi radialis brevis. 
 
3. Degenerative Process 
a. The histopathological features of 11 patients who had lateral epicondylitis 
were examined by Regan et al. They determined that the cause of lateral 
epicondylitis was more indicative of a degenerative process than an 
inflammatory process. The condition is degenerative with increased 
fibroblasts, vascular hyperplasia, proteoglycans and glycosaminoglycans, and 
disorganized and immature collagen.  
b. Repetitive eccentric or concentric overloading of the extensor muscle mass is 
thought to be the cause of this angiofibroblastic tendinosis of the ECRB. 
Epicondylitis is a degenerative condition in which increased fibrolastic activity 
and granulation tissue formation occur within the tendonxci. 
 
4. Hypovascularity 
a. Because this tendinous region contains areas that are relatively hypovascular, 
the tendinous unit is unable to respond adequately to repetitive forces 
transmitted through the muscle, resulting in declining functional tolerancexcii.  
 
Symptoms 
The most prominent symptom of epicondylitis lateralis is pain, this pain can be produced by 
palpation on the extensor muscles origin on the lateral epicondyle. The pain can radiate 
upwards along the upper arm and downwards along the outside of the forearm and in rare 
cases even to the third and fourth fingers. It is also often seen that the flexibility and strength 
in the wrist extensor and posterior shoulder muscles are deficientxciii. 
Furthermore, it is also often seen that the flexibility and strength in the wrist extensor and 
posterior shoulder muscles are deficient. At least patients report weakness in their grip 
strength or difficulty carrying objects in their hand, especially with the elbow extended. This 
weakness is due to finger extensor and supinator weaknessxciv. 
 
Symptoms last, on average, from 2 weeks to 2 years. 89% of the patients recover within 1 
year without any treatment except perhaps avoidance of the painful movementsxcv. 
  

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Subjective Assessment 
▪ 
Onset of pain 24-72 hours after provocative activity involving wrist extension 
▪ 
Pain may radiate down forearm as far as the wrist and hand 
▪ 
Difficulty with lift and grip (Pain+/- weakness) 
  
Objective Assessmentxcvi 
▪ 
Pain and point tenderness over lateral epicondyle and/or 1-2cm distal to 
epicondyle 
▪ 
Pain and weakness on resisted wrist extension 
▪ 
Weakness on grip strength testing (Dynamometer) 
▪ 
Pain and/or decreased movement on passive elbow extension, wrist flexion and 
ulnar deviation and pronation 
▪ 
Weak elbow extensors and flexors 
  
Differential Diagnosis 
▪ 
Radial Tunnel Syndrome 
▪ 
Pain in the posterolateral area of the forearm  
▪ 
Pain sometimes spreads to the dorsal side of the wrist 
▪ 
Parasthesia 
▪ 
Weakness (overuse injuries of the musculoskeletal system) 
▪ 
Posterior Interosseus Syndrome 
▪ 
Motor deficits 
▪ 
Elbow osteoarthritis 
▪ 
Fractures 
▪ 
Distal Radial Fractures 
▪ 
Radial Head Fracture 
▪ 
Olecranon Fracture 
▪ 
Cervical Radiculopathy 
▪ 
Radiating arm pain corresponding to the dermatomes  
▪ 
Neck pain 
▪ 
Parasthesia 
▪ 
Muscle weakness in myotome 
▪ 
Reflex impairment/loss 
▪ 
Headaches 
▪ 
Scapular pain 
▪ 
Sensory and motor dysfunction in upper extremities and neck 
▪ 
Cervical Disc Disease 
▪ 
Cervical Myofascial Pain 
▪ 
Cervical Spondylosis 
▪ 
Fibromyalgia 
▪ 
Medial Epicondylitis 
 
Diagnosis 
The diagnosis of lateral epicondylitis is substantiated by tenderness over the ECRB or 
common extensor origin. By the following methods, the therapist or physiotherapist should be 
able to reproduce the typical pain.  To examine the severity of the tennis elbow, there is a 
dynamometer for strength and the patients must rate their levels of tennis elbow pain and 
disability from 0 to 10. 
  
Treatment Options 
Non-Operative medical management of lateral epicondylitis is initially based on the following 
principles: relieving pain and controlling inflammation. Relieving pain can be countered by 

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rest and avoiding painful activities. Inflammation on the other hand can be prevented by 
NSAIDs in the acute cases. The use of ice three times per day for 15 minutes is also 
recommended because it reduces the inflammatory response by decreasing the level of 
chemical activity and by vasoconstriction, which reduces the swelling. Elevation of the 
extremity is also indicated if an edema of the wrist or fingers is present. 
 
The use of an elbow counterforce brace can be helpful because it plays the role of a 
secondary muscle attachment site and relieves tension on the insertion at the lateral 
epicondyle. The brace is applied around the forearm (below the head of the radius) and is 
tightened enough so that, when the patient contracts the wrist extensors, he or she does not 
fully contract the muscles. 
 
Injections should be given subperiosteally to the extensor brevis origin. These injections 
have an early and beneficial effect. During the initial 24-28 hours, increased pain be 
experienced. A steroid injection should be followed by 1-2 weeks’ rest and should not be 
repeated more than 2 times. Steroid injection seems to be effective for about 3 months, 
indicating that the patient must continue with the exercise program. 
  
Surgical treatment: 
If the symptoms of epicondylitis lateralis will prove to be resistant surgical treatment is 
indicated. Usually this is after a failed conservative treatment for more than 6 months. Most 
surgical procedures for tennis elbow involve removing diseased muscle and reattaching 
healthy muscle back to bone. The right surgical approach for you will depend on a range of 
factors. These include the scope of your injury, your general health, and your personal 
needs. 
  
Physical Therapy may include: 
▪ 
Ultrasound 
▪ 
Transcutaneous electrical nerve stimulation (TENS) 
▪ 
Braces/Splints/Straps 
▪ 
Extracorporeal Shockwave therapy 
▪ 
Deep transverse frictions for tennis elbow 
▪ 
Exercise therapy 
▪ 
Stretching 
▪ 
Eccentric exercises  
  
Current treatments for pain have yielded mixed results. Pain relief and anti-inflammatory 
medications remain the primary treatment option of choice; however, only about half of 
patients who take prescription and/or over-the-counter medication for chronic pain reported 
ineffective pain relief.  Additionally, prescription painkiller use abuse and addiction rates are 
very high and a major contributor to unintentional drug deaths.  
 
STUDY DESIGN 
 
A multi-center, triple-blind, placebo-controlled, randomized evaluation of the effect of the 
MR5® Prototype Device for temporary adjunctive use to relieve pain associated with Lateral 
Epicondylitis. 
 
SUBJECT GROUPS  
Each subject will be randomized to one of two test procedure as follows: 
 

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Test procedure groups:  
A. Subjects randomized to the test procedure group 1 will receive the study procedures 
with the active (true) Multi Radiance Medical® MR5® Prototype Device (light only).  
B. Subjects randomized to the control procedure group will receive the study procedures 
with a ‘fake’ (placebo) Multi Radiance Medical® MR5® Prototype Device.   
 
The ‘fake’ (placebo) MR5 Prototype device will appear to the subject to be an active device 
but will not produce any therapeutic light output. The placebo laser device is designed to 
have the same physical appearance as the actual (active test) device, including the 
appearance of any visible light output. Therefore, both the test and control devices emit light 
when activated that is indistinguishable to the subject. As the laser light does not put out any 
notable degree of heat or noise, these are not distinguishing factors for subjects between the 
active and control devices.  
 
Apart from the distinction of whether the subject receives the study procedures with the 
actual or the fake laser device, all subjects and investigative parties will adhere to all phases 
of the entire protocol design.   
 
SUBJECTS  
Recruitment   
Subjects will be recruited from three different sites and among the licensed health care 
provider’s test site’s pool of patients who are currently being treated for, or who are seeking 
treatment for Lateral Epicondylitis, or from patients who respond to the following recruitment 
materials, if needed.  
 
Flyer 
 
 
WANTED 
 
ADULTS WITH LATERAL EPICONDYLITIS, ONGOING  
FOR ONE MONTH, FOR A CLINICAL STUDY  
OF THE EFFECTS OF LOW-LEVEL LASER LIGHT ON REDUCING LATERAL 
EPICONDYLITIS. 
 
THIS STUDY INVOLVES SIX LASER LIGHT PROCEDURES, TWO TIMES A WEEKS FOR 
THREE WEEKS WITH THE MULTI RADIANCE MEDICAL® MR5® LASER AT THE TEST 
SITE.  
 
THERE IS THREE VISITS PRIOR TO LASER LIGHT PROCEDURES WITH ONE MORE 
VISIT TO THE TEST SITE  
ONE MONTH AFTER THE LAST LASER LIGHT PROCEDURE. 
 
YOU WILL RECEIVE $450 IF YOU FINISH THE STUDY. 
FOR MORE INFORMATION PLEASE CONTACT: 
 
<PI name> 
<test site name & location> 
<phone # and/or e-mail> 

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Newspaper Ad 
 
Lateral Epicondylitis 
Research Study 
 
This study is to see if the Multi Radiance Medical® MR5® 
LASER, a non-invasive, investigational device that uses low-
level laser light, can help to relieve symptoms of Lateral 
Epicondylitis pain longer than one month in duration. 
 
The study involves ten visits to a test site and recording 
some information at home. 
 
You will receive $450 if you finish the study. Please contact 
<PI name> at 
<test site name & location> at  
<phone and/or e-mail> for details. 
 
Compensation  
A subject will be paid a stipend of $450.00 USD for their participation in the study upon 
completion. Subjects will not be charged for the cost of the study procedures administered 
with the Multi Radiance Medical® MR5® Prototype Device for the cost of any other directly 
related evaluations or measurements that occur as part of his or her participation in the 
study. 
 
Sample size  
There will be 60 subjects evaluated for eligibility in this clinical study: 
 
▪ 
30 subjects in the active procedure group 
▪ 
30 subjects in the control procedure group (Placebo) 
 
Rationale for sample size 
Based on the following parameters established for the purposes of assessing efficacy of the 
Multi Radiance Medical MR5 Prototype Device in this clinical study using the Fischer’s Exact 
test to assess the primary endpoint. 
 
▪ 
Individual subject success criteria is defined as a 30% or greater reduction in 
self-reported Degree of Pain rating on the 0-100 VAS from baseline to study 
endpoint evaluation.  
▪ 
Overall study success criteria of at least a 30% difference between the test 
device group and the placebo group, comparing the proportion of individual 
successes in each group.  
▪ 
It is anticipated that about 50% of subjects in the test device group and about 
20% of subjects in the placebo group will meet the individual success criteria, 
and 
▪ 
Intended application of a two-tailed test with an alpha value of 0.05 and Power 
of 0.8 
 
 
 

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▪ 
the sample size of 25 available subjects per group (test group and the control 
group, separately) has been determined using the following reference 
calculator: Hypothesis Testing: Categorical Data - Estimation of Sample Size 
and Power for Comparing Two Binomial Proportions in Bernard Rosner's 
Fundamentals of Biostatistics. 
 
For the purposes of sample size calculation, a subject loss-to-follow-up of 20% is anticipated. 
 
Therefore, a minimum starting sample size of 30 evaluable subjects in each group is needed 
to ensure that a sufficient number remains at the end of the trial (25 subjects per group) for 
any significant differences found between groups to be considered statistically valid and 
representative of the general population being sampled. This results in a total of 60 subjects 
being enrolled in this study across both study procedure groups.  
 
RANDOMIZATION 
Subject allocation to procedure group will be via variable block randomization with varying 
block sizes of two and four used at random to minimize the likelihood of predicting the next 
procedure group assignment. In addition, randomization will be stratified by Fitzpatrick Skin 
Type grouping 
 
Randomization will be attained using computer generation sequence methodology, ensuring 
that the randomization methodology and the generated allocation sequence is concealed 
from the investigator and subjects.  
 
Concealment will be insured as follows: 
▪ 
Each computer-generated randomization sequence is unique and will 
therefore not be able to be replicated. 
▪ 
Randomization will occur to either ‘Test Group A’ or ‘B’ rather than to a tests 
or placebo group, and only the study Sponsor will know which assignment 
corresponds to the active devices and which corresponds to the fake device. 
The Sponsor will not reveal this information to any source (investigators, 
subjects, or study Monitor) until the final study data analysis is complete. 
 
 
TRIPLE BLIND DESIGN  
This clinical study will be a triple-blind design, such that neither the subject, nor the assessor, 
nor the therapists will be aware of whether a subject is receiving the study procedure with the 
active (test procedure group assignment) or the ‘fake’ (placebo procedure group assignment) 
Multi Radiance Medical MR5 Prototype Device until after the study is completed.  
Maintenance of study triple-blind throughout the entire course of the study will be achieved 
through the following means: 
 
1) Each subject will be randomly assigned to ‘Test Group A’ or ‘B’ by the independent study 
Monitor. Only the study Sponsor will know which label ‘Test Group A’ or ‘B’) corresponds 
to the actual (test) MR5 device and which label corresponds to the ‘fake’ device until the 
final study data analysis is complete. The Sponsor will ensure that this information is 
stored and maintained confidentially at the Sponsor’s work site. This knowledge will not 
be shared with the investigators, the subjects, or the study Monitor until the final data 
analysis is complete. 
2) The fake (placebo) MR5 device is designed to have the same physical appearance as 
the actual MR5 device, including the appearance of any visible light output. Therefore, 
both the test and sham devices emit light when activated that is indistinguishable to both 

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the subject and to the investigator. As the laser light does not put out any notable degree 
of heat or noise, these are not distinguishing factors for subjects between the four 
groups.  
3) There will be two independent investigators interacting with subjects at each test site:  
i. 
Administration investigator: who will be responsible for administrating 
the study procedures; and  
ii. 
Assessment investigator: who will be responsible for recording the 
study outcome measures 
Only the administration investigator will be aware of whether a subject is assigned to 
‘Test Group A’ or ‘B’, although he or she will not be made aware of whether ‘Test Group 
A’ or ‘B’ corresponds to the true or fake laser. Neither the assessment investigator nor 
the subject will be aware of the subject’s A/B Group assignment. In this way, the 
assessment investigator will not be able to form an association between A/B Procedure 
Group and active/sham device over the course of the study if a treatment effect is 
observed. 
4) During the MR5 procedures, both the subject and the administration investigator will wear 
Laser Safety Industries protective eyewear that filter out the laser light spectrum. 
 
 
TABLE OF SUBJECT EVENTS 
 
The following table provides a progressive summary of subject events throughout this study.  
 
PRE-PROCEDURE ACTIVITIES  
 
1. A potentially well-suited and interested candidate for participation in the study attends 
the investigator’s office. 
2. The investigator reviews the informed consent form with the candidate.  
3. If the candidate continues to be interested and voluntarily signs the informed consent 
form, the study qualification evaluation phase of the study is performed. 
4. A qualified subject is randomly assigned to procedure group. 
5. One-week individualized pain management regimen stabilization phase occurs 
6. The following measures are recorded during the Stabilization Phase: 
▪ 
Subject Daily Diary 
▪ 
Degree of Pain Ratings on final three days   
 
PRE-PROCEDURE ASSESSMENT PHASE 
 
CONTINUED STUDY ELIGIBILITY EVALUATION  
▪ 
Review of application of individualized pain management regimen throughout the 
Stabilization Phase 
▪ 
Evaluation of 3-day average VAS rating  
 
PRE-PROCEDURE MEASURES 
▪ 
Degree of Pain Rating 
▪ 
PRTEE, Grip Strength and TNFa measurements  
 
PRE-PROCEDURE VARIABLES 
▪ 
Baseline concomitant medication and treatment/therapy use 

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▪ 
Historical pain medication and treatment/therapy use 
▪ 
Baseline Lateral Epicondylitis pain variables 
▪ 
Demographics 
PROCEDURE ADMINISTRATION PHASE  
 
Six 9-minute study procedure administrations with the Multi Radiance Medical® Prototype 
Device, two procedure administrations a week for three consecutive weeks administered at the 
test site. 
 
 
PROCEDURE ADMINISTRATION PHASE MEASURES 
 
DAILY THROUGHOUT THE THREE-WEEK PROCEDURE ADMINISTRATION PHASE 
▪ 
Maintenance of the individualized pain management regimen, as needed  
▪ 
Subject Daily Diary 
 
WITHIN 24 HOURS OF COMPLETION OF THE FINAL PROCEDURE ADMINISTRATION 
▪ 
Degree of Pain Rating 
▪ 
PRTEE, Grip Strength and TNFa measurements 
▪ 
Subject Satisfaction with Overall Outcome Rating 
▪ 
Perceived Group Assignment 
▪ 
Investigator Adverse Events Evaluation  
 
POST-PROCEDURE ADMINISTRATION PHASE 
 
DAILY THROUGHOUT THE ONE MONTH POST-PROCEDURE ADMINISTRATION PHASE 
▪ 
Maintenance of the individualized pain management regimen, as needed 
▪ 
Subject Daily Diary  
 
ONE MONTH (30 DAYS) POST-PROCEDURE ADMINISTRATION PHASE (TEST SITE 
VISIT)  
▪ 
Degree of Pain Rating 
▪ 
PRTEE, Grip Strength and TNFa measurements 
▪ 
Subject Satisfaction with Overall Outcome Rating 
▪ 
Perceived Group Assignment 
▪ 
Investigator Adverse Events Evaluation  
 
 
 
 

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STUDY PROCEDURE 
 
PRIMARY OUTCOME MEASURE: 
The following is a listing of the study measurement tools to be used in this study. At each 
evaluation point, the precise tools from this list that will be employed will be specified.  
 
DEGREE OF PAIN RATING: Subjects will be asked to rate the overall degree of pain they 
are currently experiencing in the Lateral Epidondyle region on the following 0-100 0 cm (100 
mm) horizontal Visual Analog Pain Scale (VAS). 
 
The Visual Analog Pain Scale is one of the three most commonly used scales for assessing 
chronic pain. It is a simple scale that consists of a line anchored at one end by a label such 
as "NO PAIN" and at the other end "WORST POSSIBLE PAIN". The subject marks on the 
line the spot for the pain intensity, which is then measured.  
 
Standard guidelines for effective use of the VAS that are followed in this clinical study are: 
1) The line should be 10 cm long, as other lengths are less reliable.  
2) There should be a small vertical mark at each end and a verbal description.  
3) The verbal description must be in absolute terms (e.g. worst discomfort 
imaginable); 
4) The line itself should be clear of any markings and should be horizontal rather 
than vertical, for more reliable measurements.  
 
Used in the above way, it has been shown that the VAS is a proper ratio scale. Like a 
thermometer, this means that its two ends are rooted, and a doubling of the score does 
accurately reflect a doubling of the pain. Consequently, sensitive t-tests and ANOVA 
methods can be used in the analysis, so that significant differences can be identified with 
relatively small sample sizes or small differences between groups.  
Source: Measuring Pain by Adrian White, Acupuncture in Medicine, November 1998 – Vol 16 
No. 2 
 
The subject will be instructed not to record a VAS pain rating (whenever indicated) any 
sooner than four hours after having consumed a dosage of any pain relief medication. This is 
to ensure that the effect of the pain relief medication does not influence the effect of the 
study procedures with the Multi Radiance Medical MR5 Prototype Device. That is, a VAS 
rating is only to be recorded once the effect of any previously consumed pain relief 
medication has dissipated. The subject may take another dosage of his or her study-
approved pain relief medication immediately after recording the VAS rating, if needed.  
 
Throughout the course of his or her study participation, a subject can continue to take any 
other over-the-counter and/or prescription medication(s) that he or she usually takes for any 
other (non-pain relief) indication(s), as he or she usually takes them, as reported at Baseline 
evaluation and approved by the study investigator. Subjects will be required to record 
consumption of all medication throughout the course of study participation. 
 

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SECONDARY OUTCOMES 
 
Patient Related Tennis Elbow Evaluation - PRTEE 
The PRTEE, formerly known as the Patient-Rated Forearm Evaluation Questionnaire 
(PRFEQ), is a 15-item questionnaire designed to measure forearm pain and disability in 
patients with lateral epicondylitis (also known as “tennis elbow”). The PRTEE allows patients 
to rate their levels of tennis elbow pain and disability from 0 to 10, and consists of 2 
subscales: PAIN subscale (0 = no pain, 10 = worst imaginable) and FUNCTION subscale (0 
= no difficulty, 10 = unable to do) In addition to the individual subscale scores, a total score 
can be computed on a scale of 100 (0 = no disability), where pain and functional problems 
are weighted equally.  
 
The PRTEE is a reliable, reproducible, and sensitive instrument for assessment of chronic 
lateral elbow tendinopathy. It is at least as sensitive to change as Visual Analog Scale (VAS); 
the Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire, and the Upper 
Extremity Function Scale. The PRTEE may become the standard primary outcome measure 
in research of tennis elbow.xcvii 
 
For a group using the questionnaire, mean PRTEE score reductions of at least 11 points - or 
an improvement of 37% on the mean baseline score - is necessary to consider that a 
substantial improvement has taken place. Using a less stringent criterion, falls of 7 points or 
22% of the baseline score can be interpreted as indicating a limited but meaningful 
improvement.xcviii 
 
Grip Strength Test 
The grip strength will be measured using a digital grip dynamometer type Jamar® Plus 
Digital Hand Dynamometer (Patterson Medical, Warrenville, IL, USA). The grip dynamometer 
will be placed on the second knuckle of the finger to measure the grip strength between the 
thumb and the other fingers, and the subject will grip the grip dynamometer for five seconds 
within the range where no pain will be felt, with both arms naturally lowered while ensuring 
that the grip dynamometer will not be shaken or put into contact with the body. This 
measurement will be conducted three times and the average value will be used (Lee et al. 
2018).  
Lee JH, Kim TH, Lim KB. Effects of eccentric control exercise for wrist extensor and shoulder 
stabilization exercise on the pain and functions of tennis elbow. J Phys Ther Sci. 2018; 
30(4):590-594. 
 
TNF-α Marker - Blood Collection  
Blood samples (5 ml) will be collected by puncture of the antecubital vein. The collections will 
be performed by a qualified professional who will use sterile gloves, disposable syringes and 
needles. The collected material will be placed in centrifuge tubes. Fifteen minutes after 
obtaining the blood sample, it will be centrifuged and the supernatant (serum) stored at -80°C 
for further analysis. An analysis of the concentration the inflammatory marker the cytokine 
TNF-α (Tumor Necrosis Factor-alpha) will be performed by means of the enzyme-linked 
immunosorbent assay (ELISA), following the instructions of the commercial kit. 
 
1) Risks and discomforts: Blood collection can generate discomfort at the puncture 
site (antecubital vein) during the procedure and for a few minutes later. A mild 
hematoma may occur at the puncture site after the procedure. 
 

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2) Inclusion and Exclusion Criteria: Subjects with hemophilia or any type of blood 
clotting disorder, or diagnosed with a chronic immune impairment, will be 
excluded from the study. 
 
BACKGROUND/RATIONALE: EPICONDYLITIS - TNF-α 
It is known that matrix remodeling is being enabled by the balance of matrix 
metalloproteinases (MMPs) and their inhibitors. The imbalance in the expression of MMPs 
and inhibitors can contribute to tendon matrix degradationxcix,c. The tendon matrix 
degradation is initiated by MMPs and involves the release of inflammatory cytokines such as 
tumor necrosis factor (TNF-α) and interleukins as IL-1, IL-6 and IL-10ci. The presence of 
these cytokines is directly related to the progression of inflammation and painful processes 
after tendon disordercii,ciii.  
 
TNF- α is a pleiotropic cytokine related to cell survival and proliferation but also to cell death 
in the apoptotic process expressed by tenocytes in inflammatory conditionsciv. It may be the 
key cytokine in the origin of several musculoskeletal diseases such as arthritis and tendinitis, 
the TNF-α expression is increased in tendons with installed inflammatory processes, such as 
after surgery or injuriescv.. The long persistence of inflammation can increase the pro-
inflammatory mediators extending the inflammatory phases and favoring the outbreak of scar 
tissues which alter the characteristics of original tendoncvi. So, in this context, it is important 
that treatment aims to modulate the inflammation process, promoting a quality tissue repair.   
 
ADVERSE EVENTS EVALUATION:  Adverse events evaluation will include, but not be 
limited to, the following unlikely, but potentially feasibly events that may occur from 
application of the Multi Radiance Medical® MR5® Prototype Device to the treatment site: 
▪ 
skin irritation 
▪ 
discoloring 
▪ 
rash 
▪ 
indentations 
▪ 
infection 
▪ 
increased pain or tenderness  
 
SUBJECT SATISFACTION WITH OVERALL OUTCOME RATING: The subject is asked to 
indicate how satisfied he or she is with any change in his or her Lateral Epicondylitis pain 
following completion of the procedure administrations with the MR5®, by responding to the 
following question by selecting the most appropriate category from the following five-point 
Likert scale: “How satisfied or dissatisfied are you with any change you may have noticed in 
the pain in your neck/shoulder after getting the procedures with the study device?” 
 
✓ Very Satisfied 
✓ Somewhat Satisfied 
✓ Neither Satisfied nor Dissatisfied 
✓ Not Very Satisfied 
✓ Not at All Satisfied   
 
PERCEIVED GROUP ASSIGNMENT: The subject, the Administration Investigator and the 
Assessment Investigator will each be asked (separately) to state whether he or she believes 
the subject to have received the active procedure administrations with the actual Multi 
Radiance Medical® MR5® Prototype Device or the ‘fake’ procedures with the ‘placebo’ 
MR5® device, and the reasons for those beliefs.   
  
 
 

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STUDY PROCEDURE PROTOCOLS 
 
All study procedure protocol activities listed below will be conducted by a licensed health 
care provider at the test site. The study licensed health care provider will be a suitably 
qualified and licensed medical/healthcare professional who is trained and experienced in 
treating individuals with Lateral Epicondylitis, in evaluating according to the study 
qualification parameters, in recording the study outcome measures such as range of motion 
and medication history, and in performing adverse events evaluations.   
 
PRE-PROCEDURE ACTIVITIES 
The pre-procedure activities will be conducted at the test site prior to commencement of the 
study procedure administration. 
 
STUDY QUALIFICATION 
 
ATTAINMENT OF INFORMED CONSENT PROCESS 
 
 
Informed consent is an agreement between the individual investigator (a licensed 
medical/healthcare professional) and each individual subject, having the capacity to 
understand and to make an informed decision. Informed consent is a process that is initiated 
prior to the potential subject agreeing to be considered for participation in the study and 
continues throughout the duration of the individual’s study participation. 
 
A written consent form describing in detail the purpose of the study, the study intervention, 
the study procedures, and the risks involved in taking part in the study is given to and 
reviewed with each subject, with voluntarily signed and dated documented informed consent 
required from the subject prior to starting any study subject activity, including study 
qualification evaluation. No other consent documents will be provided to subjects in this 
study. The consent form will be IEC-approved with supporting documentation. 
 
The informed consent process will occur in a private room and be between the investigator 
and the subject. 
 
The step-by-step processing for attainment of informed consent will be as follows: 
 
1. The subject will be provided with the written informed consent form and asked to carefully 
read and review the entire document or the investigator will read it to the subject if 
alternatively requested by the subject.  
 
2. The investigator will then also provide a verbal review of the written information contained 
in the consent form ensuring subject awareness of the: 
• purpose of, the intervention, and the procedures involved in, the study.  
• reasonably expected benefits the subject might receive, as well as any risks or potential 
discomfort that are involved.   
• alternative treatments available to the subject for the study condition being evaluated.   
• fact that the subject’s records will remain confidential, but that the FDA and the IEC has 
the right to inspect those records.   
• Subject’s rights as a research subject.  

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• name and method of contacting the appropriate person(s) to answer the subject’s 
questions about the research and in the event of the occurrence of a research-related 
injury. 
 
3. The investigator will emphasize to the subject that their participation in the study is strictly 
voluntary, and that they may decline to participate in the study or withdraw their consent 
to participate in the study at any time, for any reason, without prejudice, such that the 
quality of their medical care will not be adversely affected. 
 
4. The investigator will answer any questions the subject may have about the study and 
their participation in it and verify that the subject has correctly understood the information 
in the consent form.  
 
5. Subjects will be given the opportunity and encouraged to take the consent form home to 
discuss the study with their family and/or to think about it some more before signing for 
as long as desired provided enrollment is ongoing at the time the decision to sign is 
made.  
 
6. The subject must voluntarily and willingly, without coercion or duress, or force or 
influence from the investigator or sponsor or any other party, sign and date the written 
informed consent document that is witnessed and verified by the investigator’s dated 
signature prior to commencement of any study procedures or activities.  
 
7. A copy of the informed consent document will then be given to the subject for their 
records.  
 
8. Completion of the informed consent process will be documented in the source document 
(CRF), and the subject and investigator signed and dated consent form will be filed 
according to the procedure in the site’s Informed Consent SOP.  
 
The informed consent form that will be used in this clinical study is contained in Appendix D. 
 
ASSIGNMENT OF SUBJECT IDENTIFICATION NUMBER 
 
The subject will be assigned a unique subject identification number based upon his or her 
order of entry into the study. 
 
Additional information about the informed consent and subject ID number assignment is 
contained in a later section of the protocol titled, “SAFETY AND CONFIDENTIALITY 
ISSUES.” 
 
STUDY QUALIFICATION EVALUATION: INCLUSIONS/EXCLUSION CRITERION 
 
INCLUSION CRITERIA 
To be eligible for study participation, a subject must satisfy each of the following criteria. 
 
Patient history: History of one or more the following: 
▪ 
Patients with a history of pain around the Lateral Epicondyle for at least 1 
month; 
▪ 
Tenderness localized to the epicondyle and anterodistal region of the 
epicondyle with palpation;  

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▪ 
2 of 4 positive results of provocative tests comprising of Maudsley’s, Cozen’s, 
Thomsen and Mill’s tests (Whaley, Baker 2004); 
▪ 
Aged between 18 and 50 years; 
▪ 
Both genders. 
Reference - Whaley AL, Baker CL. Lateral epicondylitis. Clin Sports Med. 2004; 
23(4):677-691 
Medication Use History: Where applicable, history of attaining relief from Lateral Epicondyle 
pain from taking over-the-counter and/or prescription muscle relaxants; nonsteroidal anti-
inflammatories (NSAIDs) such as ibuprofen or naproxen, and acetaminophen. 
 
Previous Records Review (x-rays, MRI, CT scans, etc.): where pre-existing and available, 
previous records review that indicates muscle or ligament injury and the absence of 
Degenerative Joint Disorder (DJD)  
 
Physical Examination of the Lateral Epicondyle Region.  
• 
Painful range of motion  
• 
Pain and weakness upon grip strength and wrist extension 
• 
Muscles in Lateral Epicondyle feel hard, tight or knotted upon palpation 
• 
Muscles in Lateral Epicondyle feel hard, tight or knotted upon palpation 
• 
Lateral Epicondyle pain is persisting over one month 
• 
Self-reported Degree of Pain rating on the 0-100 VAS pain scale for the Lateral 
Epicondyle region is 50 or greater  
• 
Subject is willing and able to maintain his or her current pre-study Lateral 
Epicondyle pain management regimen of pain relief medication and/or 
treatment/therapy use throughout the course of study duration, whilst refraining 
from consuming other OTC and/or prescription medication(s) and/or herbal 
supplements intended for the relief of pain and/or inflammation, including muscle 
relaxants,  and/or partaking in other treatments/therapies including conventional 
therapies such as physical therapy, occupational therapy and hot or cold packs, 
as well as alternative therapies such as chiropractic care and acupuncture. 
• 
18 years of age or older 
• 
Male or female 
• 
Subject is fluent in Portuguese 
 
EXCLUSION CRITERIA 
A subject who satisfies any of the following criteria will be excluded from study participation: 
• 
hemophilia or any type of blood clotting disorder 
• 
chronic immune impairment neoplasia  
• 
neurologic deficits  
• 
cervical radiculopathy  
• 
peripheral nerve disease  
• 
rheumatoid arthritis 
• 
shoulder disease  
• 
radial tunnel syndrome  
• 
previous surgery of the affected upper extremities  
• 
congenital or acquired bony deformity in the ipsilateral upper extremity  
• 
the initiation of opioid analgesia or corticosteroid or analgesic injection 
interventions within the previous 6 months  

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• 
physical therapy intervention on the upper extremity in the previous year  
• 
bilateral epicondylosis  
• 
secondary orthopedic problems. 
 
Physical Examination of the Lateral Epicondyle Region: 
• 
Lateral Epicondyle pain is acute, defined as having persisted over less than the 
last 1 month 
• 
Self-reported Degree of Pain rating on the 0-100 VAS pain scale for the Lateral 
Epicondyle region is less than 50  
• 
Local corticosteroids and/or botulinum toxin (Botox®) injection for Lateral 
Epicondyle pain relief within the prior 30 days  
• 
Medical tx; such as chiropractic care and acupuncture within last 30 days 
• 
Current, active chronic pain disease: chronic fatigue syndrome, fibromyalgia, 
endometriosis, inflammatory bowel disease, interstitial cystitis diabetic 
neuropathic pain 
• 
Cancer or treatment for cancer in the past 6 months, including tumors of the 
spinal cord 
• 
Diabetes Type 1 
• 
Significant heart conditions including CHF and implantable heart devices such as 
a pacemaker 
• 
Active infection, wound, or other external trauma to the areas to be treated with 
the laser 
• 
Medical, physical, or other contraindications for, or sensitivity to, light therapy 
• 
Pregnant, breast feeding, or planning pregnancy prior to the end of study 
participation 
• 
Serious mental health illness such as dementia or schizophrenia; psychiatric 
hospitalization in past two years 
• 
Developmental disability or cognitive impairment that in the opinion of the 
investigator would preclude adequate comprehension of the informed consent 
form and/or ability to record the necessary study measurements 
• 
Involvement in litigation and/or receiving disability benefits related in any way to 
the parameters of the study 
• 
Subject is less than 18 years of age  
• 
Participation in a clinical study or other type of research in the past 30 days 
• 
Subject is not fluent in Portuguese 
 
SUBJECT GROUP RANDOMIZATION  
A fully qualified subject is randomly assigned to ‘Test Group A’ or ‘B’ following the 
methodology outlined above in the STUDY DESIGN section of the protocol. 
 
INDIVIDUALIZED PAIN MANAGEMENT REGIMEN STABILIZATION PHASE:  
During the one-week period immediately preceding commencement of the pre-procedure 
assessment phase, subjects will partake in a pain management stabilization phase. 
See Appendix C for Individualized Pain Medication Regimen Details. 
 
ESTABLISHMENT OF PROCEDURE ADMINISTRATION VISIT SCHEDULE 
To implement consistency in the time of day when VAS pain ratings are recorded across all 
evaluation points throughout the study duration, the visit schedule times for each of the six 
procedure administration visits will be established at this time within a one-hour time frame. 
For example, between 2 p.m. and 3 p.m. for each of the six procedure administration visits, 
or between 10 a.m. and 11 a.m. for each of the six procedure administration visits, etc.  

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INDIVIDUALIZED PAIN MANAGEMENT REGIMEN STABILIZATION PHASE MEASURES 
During the two-week stabilization phase, the subject records the following, as applicable. 
 
• 
Subject Daily Diary 
• 
Degree of Pain Rating on the 0-100 VAS on each of the last three days of the 
baseline stabilization phase, each measurement to be recorded within 15 minutes of 
the procedure administration visit times scheduled. For example, if the procedure 
administration visit schedule is established as between 2 p.m. and 3 p.m., the latest 
time a required VAS recording can be made is 3:15 p.m. The subject will record the 
exact time that he or she marks the VAS recording. 
 
PRE-PROCEDURE ASSESSMENT PHASE 
 
The pre-procedure assessment phase will commence following successful completion of the 
individualized pain management regimen stabilization phase and just prior to 
commencement of the procedure administration phase. 
 
CONTINUED STUDY ELIGIBILITY EVALUATION 
Prior to the subject commencing the Pre-Procedure Assessment phase of the study, the 
investigator will: 
• 
review the subject’s recordings of use/application of his or her individualized pain 
management regimen to ensure it was correctly applied and recorded, and that there 
are no deviations significant enough to warrant withdrawal of the subject from the 
study prior to entry to the pre-procedure assessment phase; and 
• 
calculate the average of the 3 VAS degree of pain scores recorded during the last 
three days of the individualized pain management regimen stabilization phase. In 
order for the subject to proceed, the 3-day average VAS score must be 50 or greater. 
If it is less than 50, the subject’s participation in the study ends at this time. 
 
PRE-PROCEDURE MEASURES 
• 
Degree of Pain Rating. This will occur within 15 minutes prior to the initial procedure 
administration. The exact time the VAS rating is recorded will be noted. 
• 
PRTEE, Grip Strength and TNFa measurements will be noted. 
 
PRE-PROCEDURE VARIABLES 
• 
Baseline concomitant medication and treatment/therapy use 
• 
Historical pain medication and treatment/therapy use 
• 
Baseline Lateral Epicondyle pain variables 
• 
PRTEE, Grip Strength and TNFa measurements and Fitzpatrick Skin Type 
Classification will be noted. 
• 
Demographics 
 
PROCEDURE ADMINISTRATION PHASE 
 
PROCEDURE ADMINISTRATION PROTOCOL   
• 
The procedure administration phase of the study will commence within 15 minutes 
subsequent to completion of the pre-procedure assessment phase.    
• 
The procedure administration phase comprises a total of six procedure 
administrations with the Multi Radiance Medical® MR5® Prototype Device: two 

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procedures a week for three consecutive weeks*, each procedure administration 
three to four days apart. 
• 
Three weeks, 2 times a week... Follow-up at 4th week after administration phase  
• 
Emanet SK, Altan LI, Yurtkuran M. Investigation of the effect of GaAs laser therapy 
on lateral epicondylitis. Photomed Laser Surg. 2010 Jun;28(3):397-403. doi: 
10.1089/pho.2009.2555. PubMed PMID: 19877824. 
• 
Each of the six procedure administration visits will occur within the same on-hour 
timeframe, as explained above under ‘ESTABLISHMENT OF PROCEDURE 
ADMINISTRATION VISIT SCHEDULE’ above. 
• 
Each procedure administration lasts 20 minutes. 
• 
The procedure administrations with the MR5® Laser is administered by the procedure 
administrator at the test site. 
• 
Prior to administration of treatment protocol skin should be cleansed and verify there 
is no broken skin. 
 
The study procedure administration protocol is as follows: 
1. The subject enters the procedure administration room and is situated in a seated 
position.  
2. The skin should be prepared for treatment by cleansing skin and verification of no 
broken skin. 
3. The subject is correctly fitted with the safety glasses. 
4. The procedure administrator puts on the safety glasses and selects the Multi 
Radiance Medical® MR5® Prototype Device A or B according to the subject’s 
procedure group randomization.  
5. The Prototype Device emitter is statically held by direct contact with the skin on 
each of the target areas: 
Identified in diagram (over the Lateral Epicondyle) for the light administration 
phase for 60s each location. 
6. The total procedure administration duration is 5 minutes for the laser portion of the 
treatment. 

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PROCEDURE ADMINISTRATION PHASE MEASURES 
 
Daily throughout the three-week procedure administration phase, the subject will continue at 
home to: 
• 
maintain application of his or her individualized pain management regimen, as during 
the two-week stabilization phase, and 
• 
complete the Subject Daily Diary, as applicable 
 
WITHIN 24 HOURS OF COMPLETION OF THE FINAL (6TH) PROCEDURE 
ADMINISTRATION  
• 
Degree of Pain Rating. The exact time the VAS rating is recorded will be noted. 
• 
PRTEE, Grip Strength and TNFa measurements will be noted. 
• 
Subject Satisfaction with Overall Outcome Rating 
• 
Perceived Group Assignment 
• 
Investigator Adverse Events Evaluation  
 

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POST-PROCEDURE ADMINISTRATION PHASE  
    
The post-procedure administration phase encompasses the one-week period immediately 
following completion of the procedure administration phase and comprises the following 
evaluation points and associated measures.  
 
POST-PROCEDURE ADMINISTRATION PHASE EVALUATION POINTS AND 
MEASURES 
Daily throughout the one-week post-procedure administration phase, the subject will continue 
at home to: 
• 
maintain application of his or her individualized pain management regimen, as during 
the two-week stabilization phase and the three-week procedure and phase, and 
• 
complete the Subject Daily Diary, as applicable 
 
ONE MONTH POST-PROCEDURE ADMINISTRATION PHASE (TEST SITE VISIT)  
• 
Degree of Pain Rating: This time will be within the same one-hour time-frame as the 
prior post-procedure administration phase VAS ratings were recorded, 1 month after 
the final procedure administration; e.g., if the prior 3 post-procedure administration 
VAS recordings were made between 1:30 p.m. and 2:30 p.m. on each of the three 
days, then the 1 week post-procedure VAS recording will also be made between 1:30 
p.m. and 2:30 p.m. The exact time the VAS rating is recorded will be noted. 
• 
PRTEE, Grip Strength and TNFa measurements will be noted. 
• 
Subject Satisfaction with Overall Outcome Rating 
• 
Perceived Group Assignment 
• 
Investigator Adverse Events Evaluation  
 
ADVERSE EVENTS  
At each evaluation and measurement point throughout the clinical study, and at any other 
time throughout the duration of the clinical trial that is necessary, any and all potential 
adverse events reported by a subject or observed by an investigator will be recorded on the 
case report form, and subsequently evaluated by the investigator for its relation to the study 
procedure and whether or not any corrective action needs to be taken. All potential adverse 
events recorded will be appropriately reported to the governing IRB, as applicable. 
 
It is unlikely and not expected that any adverse events will result from implementation of this 
clinical study protocol. Prior clinical trials using low level laser light have not typically yielded 
any adverse events or reactions. However, potential adverse events that may feasibly occur 
from application of the Multi Radiance Medical® MR5® Prototype Device include, but are not 
necessarily limited to; skin irritation, discoloring, rash, indentations and infection. 
 
PRIVACY AND CONFIDENTIALITY 
Records for each subject in this clinical study will be maintained in separate files in a locked 
filing cabinet at the test site. The investigator at the test site will be responsible for ensuring 
that all records for a subject pertaining to his or her participation in the clinical study are 
stored in that subject’s file at all times other than when information is being recorded on 
them.   
 
The Laboratory of Phototherapy in Sports and Exercise will have access to the files for the 
purposes of data monitoring and auditing. Once the study is complete, copies of all of the 
subject case report forms will be made and supplied to Laboratory of Phototherapy in Sports 
and Exercise for analysis of results. Laboratory of Phototherapy in Sports and Exercise will 

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maintain these copies in a separate clinical study file that is kept in a locked filing cabinet on 
their premises. The original records will be maintained at the respective test sites upon 
completion of the study in their original files and stored in a locked filing cabinet.  
 
Subjects’ identities will be kept confidential by assigning each subject a subject ID upon 
acceptance into the study. The subject ID will comprise the investigator’s two initials (first and 
last name initials) and a three-digit number from 001 to 100 that will be based upon the 
subject’s order of entry into the clinical study. For example, the eighth subject to be enrolled 
at the test site would have a subject ID of EL008. Neither the study Sponsor nor Laboratory 
of Phototherapy in Sports and Exercise will receive any additional identifying information 
about a subject and will therefore have no way of linking a subject ID to a particular subject 
and his or her results.   
 
MONITORING OF THE CLINICAL STUDY 
The study Monitor will assure that the test site and the investigator is executing the protocol 
exactly as outlined and intended. This includes insuring that a signed informed consent form 
has been attained from each subject prior to commencing the protocol, and that all study 
evaluations are recorded using the specified methods and correctly and fully recorded on the 
appropriate clinical case report forms. The investigator will be trained by the same study 
Monitor to this end, including insuring that the investigator understands how to watch for, to 
evaluate and to handle, the occurrence or potential occurrence of an adverse event.  
 
STATISTICAL ANALYSIS 
 
PRIMARY EFFICACY OUTCOME MEASURE:  
CHANGE IN SUBJECT SELF-REPORTED VAS PAIN RATING FROM BASELINE TO 
STUDY ENDPOINT   
Primary efficacy outcome measure for this clinical study will be a statistically significant 
difference in the proportion of subjects between test and control groups who achieve a 
clinically meaningful and statistically significant decrease in self-reported VAS pain rating 
from baseline to study endpoint.    
 
Subjects meeting Individual Success Criteria 
The individual subject success criteria is defined as a 30% or greater decrease in self-
reported VAS pain rating at study endpoint relative to baseline. 
 
Overall Study Success Criteria.  
Overall study success criteria is defined as at least a 30% difference between procedure 
groups, comparing the proportion of individual successes in each group. It is anticipated that 
about 50% of subjects in the test group will meet the individual success criteria and about 
20% of subjects in the control group will meet the individual success criteria.  
 
Evaluation Time Points 
The study end evaluation time point at which study success will be analyzed is within 24 
hours following completion of the three-week procedure administration phase with the Multi 
Radiance Medical® MR5® Prototype Device. Study success will be evaluated at endpoint 
relative to baseline.  
 
Hypotheses 
• 
Null Hypothesis: There will be no statistically significant difference in the proportion of 
individual successes, as defined, between the test and control groups. 

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• 
Alternative Hypothesis: There will be a statistically significant difference in the 
proportion of individual successes, as defined, between the test and control groups, 
to the effect of 30% or greater. 
 
PRIMARY EFFICACY OUTCOME STATISTICAL EVALUATION METHODS 
Intent to Treat (ITT) Principle: Primary efficacy analysis will be according to the intent to treat 
(ITT) principle; wherein subjects will be included in the analysis if they were randomized to 
study procedure group, had a valid baseline (pre-procedure) visit including the required 
Lateral Epicondylitis pain VAS recordings; and received at least the first study procedure 
administration.  
 
Missing data will be handled through all of the following methods:  
• 
Last Observation Carried Forward (LOCF): by carrying forward the last recorded 
observation to fill in the subsequent missing value.  
• 
Tipping Point Analysis: Tipping point analysis will be used to examine the impact of 
missing data on the study conclusion. Tipping point analysis is defined as the 
difference in means (for continuous data) or the difference in the number of events 
(for binary data) between treatment groups in the missing cohort at which the study 
conclusion is changed. A tipping point analysis replaces the missing value with 
other values so that the resulting p-value is equal to the pre-specified significance 
level (i.e. α=0.05, 2-sided).   
• 
Multiple Imputation Analysis: Multiple imputation analysis is a strategy to handle 
missing values in a clinical trials wherein each missing value is replaced with a set 
of plausible values that represent the uncertainty about the right value to impute. 
Multiple imputation does not attempt to estimate each missing value through 
simulated values, but rather to represent a random sample of the missing values. 
This process results in valid statistical inferences that properly reﬂect the 
uncertainty that results from missing values, such as valid conﬁdence intervals for 
parameters. 
 
Multiple imputation inference involves three distinct phases: 
1. The missing data are ﬁlled in m times to generate m complete 
data sets. 
2. The m complete data sets are analyzed by using standard 
statistical procedures. 
3. The results from the m complete data sets are combined for the 
inference. 
 
Multiple imputation usually assumes that the data are missing at random (MAR). 
That is, for a variable Y, the probability that an observation is missing depends 
only on the observed values of other variables, not on the unobserved values of 
Y. 
 
Pre-Protocol Analysis will also be performed for the set of all subjects who were 
randomized to procedure group and completed the study according to the full protocol.  
 
Primary analysis of efficacy will be according to intent to treat (ITT) analysis through the 
application of: 
1) Fisher's exact test to compare the proportion of success between the test and the 
control groups, considering that randomization has been diligently conducted and 
important covariates between the two groups are well balanced. 

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2) Parametric ANCOVA model analysis with the mean change from baseline to study 
endpoint in Lateral Epicondyle pain ratings on the VAS as the dependent variable, 
procedure group as the independent variable of interest and baseline average Lateral 
Epicondyle pain VAS rating as a covariate. A two-tailed significance level of 5% will be 
considered to be statistically significant.  
 
Covariates: The following potential covariate baseline variables will be adjusted, as 
applicable, through application of an ANCOVA analysis for the continuous variables and 
linear regression analysis for categorical variables. 
• 
Baseline Lateral Epicondyle pain VAS rating 
• 
Fitzpatrick Skin Type Classification 
• 
Age   
• 
Gender 
• 
Demographics 
 
SUPPORTIVE OUTCOME MEASURES  
The following supportive outcome measures will be evaluated: 
 
a. Mean and individual subject changes in Degree of Pain VAS ratings across and 
between all study evaluation time points, within and between procedure groups 
b. Mean and individual subject changes in each of the PRTEE, grip strength and TNFa 
levels measurements across and between all evaluation points, within and between 
procedure groups 
c. Differences in satisfaction with Study Outcome Ratings between procedure groups at 
both evaluated time points, and any change between   
 
SUPPORTIVE MEASURES STATISTICAL EVALUATION METHODS 
a. Supportive measures that are continuous variables will be analyzed through 
parametric analysis using ANCOVA. A two-way significance level of 5% will be 
statistically significant.  
b. Supportive measures that are categorical will be evaluated through linear regression 
analysis. 
c. Satisfaction with Study Outcome Ratings: will be tabulated according to category and 
reported as percentages. Satisfaction levels will be correlated with subject individual 
study success and recorded changes in Lateral Epicondyle pain VAS ratings from 
baseline to endpoint evaluations.  
 
STATISTICAL EVALUATION OF APPLICATION OF PAIN MANAGEMENT REGIMEN 
The impact of pain management regimen use on the study outcome measure will be 
evaluated through application of the following analyses: 
 
a. Fisher's exact test to compare the proportion of subjects requiring use of his or her 
individualized pain management regimen between the test and the control groups. 
b. Parametric ANCOVA model analysis with the mean change from baseline to study 
endpoint in Lateral Epicondyle pain ratings on the VAS as the dependent variable, 
procedure group as the independent variable of interest and average 
dosage/frequency of use any component of the individualized pain management 
regimen. A two-tailed significance level of 5% will be considered to be statistically 
significant.  
c. T-test analysis to compare the frequency of usage of the pain management regimen 
across study duration between treatment groups.   

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d. Linear regression analysis to evaluate the impact of frequency of usage of the pain 
management regimen across study duration on the primary outcome measure 
between procedure groups 
e. Log Rank statistics to evaluate differences in the time to first use of the pain 
management regimen between test and placebo procedure groups   
 
 
BLINDING EFFICACY EVALUATION  
Statistical evaluation of blinding efficacy will be performed as follows: 
 
(i) The percentage of subjects who correctly perceived their procedure group assignment 
and the percentage of subjects who did not correctly perceive their procedure group 
assignment will be calculated. 
(ii) The percentage of times the administration investigators correctly perceived subjects’ 
procedure group assignment and the percentage of times the assessment investigators 
did not correctly perceive subjects’ procedure group assignment will be calculated. 
(iii) The percentage of times the assessment investigators correctly perceived subjects’ 
procedure group assignment and the percentage of times the assessment investigators 
did not correctly perceive subjects’ procedure group assignment will be calculated. 
(iv) The Fischer’s Exact categorical analysis technique for comparison of proportion of 
successes (accurate procedure group assignment determination) and failures (inaccurate 
procedure group assignment determination) between subject groups will be performed for 
each of the subject, administration investigator and assessment investigator 
determinations. 
• 
Comparisons will be made to evaluate if the proportion of correctly guessed 
subject procedure group assignments is greater than the proportion of incorrectly 
guessed subject group assignments. 
• 
Comparison will be made for each of the groups of subjects, administration 
investigators and assessment investigators, within and between treatment groups.  
• 
In performing these evaluations, the numerical design and analysis of the blinding 
assessment will follow that outlined in Bang, et al. (Bang H, Ni L, Davis CE, 
Assessment of blinding in clinical trials. Control Clin Trials. 2004; 25:143-56)  
(v) Qualitative analysis confirmation: Evaluation of the comments provided by the subject, 
administration investigators and assessment investigators in the rationale section to 
explain the guess at group alignment will be evaluated and interpreted as follows to either 
support or negate the numerical findings:   
• 
Positive blinding efficacy will be supported through qualitative assessment of 
comments provided to support perceived group assignment that pertain to the 
determination being made based on treatment efficacy or lack thereof; e.g.: ‘I can 
move my head from side to side easily and without it hurting and I couldn’t do that 
before, so I believe I got the real treatment’ or ‘I haven’t noticed any change in my 
Lateral Epicondyle pain, so I believe I got the fake treatment.’ 
• 
Blinding will be determined to have failed if comments provided to support 
perceived group assignment pertain to factors such as sensation/visual clues, such 
as ‘I saw/didn’t see a light go on’, or other factors that pertain to blinding having 
been compromised such as ‘I overheard the doctor saying I wasn’t getting the real 
treatment.’ 
 
Sample stratification distribution plan 
 
Sample Stratification 

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In order to account for the possibility that skin phototype could affect the absorption of the 
energy emitted from the study device, and to ensure that the study sample is representative 
of the range of skin phototypes in the intended U.S. clinical patient population, recruitment 
and enrollment of the final 50 study subjects will be further stratified by Fitzpatrick skin type, 
as determined according to race, according to the process of proportionate allocation using a 
sampling fraction in each of the strata that is proportional to that of the total sample 
population. 
 
According to the United States Census Bureau (www.census.gov), the distribution of race 
throughout the United States population as of 2014 is as follows: 
- 
White (not Hispanic/Latino): 62% 
- 
Hispanic/Latino: 17% 
- 
African American: 13% 
- 
Asian: 5% 
- 
Other (including Hawaiian/Pacific Islander, America Indian, Alaskan and 2+ races): 
3% 
 
Applying stratification according to the process of proportionate allocation using a sampling 
fraction in each of the strata that is proportional to that of the total sample population, the 
following formula is applied: 
 
X = x1*X + x2*X + x3*X + x4*X + x5*X; where 
• X = Total Sample Population = 50 subjects 
• x1 = Subpopulation: White = 0.62; 0.62*50 = 31 subjects 
• x2 = Subpopulation: Hispanic/Latino = 0.17; 0.17*50 = 8.5 subjects 
• x3 = Subpopulation: African American = 0.13; 0.13*50 = 6.5 subjects 
• x4 = Subpopulation: Asian = 0.05; 0.05*50 = 2.5 subjects 
• x5 = Subpopulation: Other = 0.03; 0.03*50 = 1.5 subjects 
 
Furthermore, in the following reference … 
Sauer’s Manual of Skin Disease; Brian J Hall, John C. Hall; 2012 
Chapter 35: Skin Disease in Ethnic Skin; Cheryl M Burgess, MD & Beverly A. Johnson, MD 
… Fitzpatrick Skin Type is associated with race, as follows: 
 
• “White”: (Not Hispanic/Latino): Fitzpatrick Skin Types I, II &III 
• “Ethnic” (Hispanic/Latino; African American, Asian): Fitzpatrick Skin Types IV, V & VI 
 
In consideration of the distribution of race in the U.S population as determined above, this 
results in the need to recruit: 
Ø 31 subjects with Fitzpatrick Skin Type I, II or III 
Ø 19 subjects with Fitzpatrick Skin Type IV, V or VI (17 Hispanic/Latino+13 African 
American+5 Asian+3 ‘Other’) 
 
For ease and uniformity of randomization, given that there will be three test sites, and two 
procedure administration groups the sampling plan is rounded to even numbers within 
individual groups, as follows: 
 
 
 
Test Site #1 
 
Skin Type I, II & III 
Skin Type IV, V & VI 
Test Group 
7 
5 
Placebo Group 
8 
4 

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Test Site #2 
 
Skin Type I, II & III 
Skin Type IV, V & VI 
Test Group 
4 
3 
Placebo Group 
4 
3 
 
 
 
Test Site #3 
 
Skin Type I, II & III 
Skin Type IV, V & VI 
Test Group 
4 
2 
Placebo Group 
4 
2 
 
 
While every effort will between made to recruit subjects evenly across the range of 
Fitzpatrick Skin Types within each of the two categories, it is anticipated that the majority of 
recruited Skin Types will fall within the range of II to V, inclusive, proportionate within the 
respective categories, as Fitzpatrick Skin Types I and VI and the least predominant Skin 
Types amongst the U.S. population. 
 
Once a Fitzpatrick Skin Type category has been filled at a test site, no additional subjects will 
be enrolled in that category at that site. 
 
 
FITZPATRICK SKIN TYPE CLASSIFICATION SCALE: The Fitzpatrick Skin Type 
Classification Scale is a numerical classification schema for human skin color developed in 
1975 by Harvard Medical School dermatologist, Thomas Fitzpatrick, MD, PhD. The scale 
classifies a person's complexion and their tolerance of sunlight. 
 
The Fitzpatrick Classification Scale classifies skin type from I through VI according to the 
applicable criteria contained in the chart below. 
 
Skin 
Type 
Skin Color 
Characteristics 
I 
White; very fair; red or blond hair; blue eyes; 
freckles 
Always burns, never tans 
II 
White; fair; red or blond hair; blue, hazel, or green 
eyes 
Usually burns, tans with difficulty 
III 
Cream white; fair with any eye or hair color; very 
common 
Sometimes mild burn, gradually 
tans 
IV 
Brown; typical Mediterranean Caucasian skin 
Rarely burns, tans with ease 
V 
Dark Brown; mid-eastern skin types 
very rarely burns, tans very easily 
VI 
Black 
Never burns, tans very easily 

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POOLABILITY EVALUATION  
The primary efficacy outcome is a binary variable, with success defined as a 30% or greater 
reduction in self-reported Degree of Pain rating on the 0-100 VAS from baseline to study 
endpoint evaluation. Poolability analysis for this primary binary outcome will be via the 
Breslow-Day test for homogeneity of odds ratios. 
Furthermore, poolability analysis will also be conducted for the continuous outcome of mean 
change from baseline to study endpoint in self-reported Degree of Pain ratings on the 0-100 
VAS through a treatment-by-subgroup interaction term applying a logistic regression model 
that also includes the main effect terms of all treatment groups.  
 
SAFETY ANALYSES  
Safety analyses will be based on all subjects who were randomized to the test or to the 
placebo procedure group. Safety will be assessed by evaluating and comparing frequency 
and incidence of observed and/or reported adverse events between test and placebo 
procedure groups. A chi-square test with a continuity correction will be performed to compare 
the percentage of subjects who had adverse events between test and placebo group 
subjects.  
 
 
CASE REPORT FORMS 
The case report forms that will be used to collect the data from each subject in this clinical 
study can be found in Appendix E. 
 
 
 

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lxxiii Xavier M, de Souza RA, Pires VA, Santos AP, Aimbire F, Silva JA Jr., Albertini R, Villaverde AB. Low-level light-emitting diode therapy 
increases mRNA expressions of IL-10 and type I and III collagens on Achilles tendinitis in rats. Lasers Med Sci. 2014;29:85-90. 
 

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