The Effects of Cranial Laser Reflex Technique on Hamstring Flexibility, Strength, and Pain Pressure Threshold: a Pilot Study
Phase: NA
Conditions: Hamstring Injury, Muscle Tone Increased, Muscle Pain, Muscle Weakness
Sponsor: University of North Carolina, Chapel Hill

 
Study Title 
The effect of Cranial Laser Reflex Technique on hamstring function: a pilot study 
 
NCT number: 03044106 
 
 
Document Date: Jan 25, 2017 
 
 

 
 
 
 
 
 
Master Protocol  
CLRT for Hamstring Flexibility 
and Strength 
  
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MASTER PROTOCOL 
THE EFFECT OF CRANIAL LASER REFLEX TECHNIQUE ON 
HAMSTRING FLEXIBILITY, STRENGTH AND PAIN 
PRESSURE THRESHOLD: A PILOT STUDY 

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PROTOCOL  
Title: The Effects of Cranial Laser Reflex Technique (CLRT) on Hamstring Flexibility, 
Strength and Pain Pressure Threshold: a pilot study 
 
Principal Investigator:  
Nicholas A. Wise, D.C.  
T32 Postdoctoral Research Fellow 
University of North Carolina Program on Integrative Medicine 
Department of Physical Medicine and Rehabilitation, Chapel Hill, NC   
  
Supported by:  
NC TraCS 
NCCIH T32 Fellowship 
 
  
Sponsor of IND (IDE):  
None Required  
 

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TOOL REVISION HISTORY 
Version Number: 1.1 
Version Date: January 25, 2017 
 

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Table of Contents 
PROTOCOL ............................................................................................................................................... 1 
TOOL REVISION HISTORY .......................................................................................................................... 2 
Version Number: 1.1 ...............................................................................................................................................2 
STUDY TEAM ROSTER ............................................................................................................................... 7 
Principal Investigator...............................................................................................................................................7 
Co-Investigators .......................................................................................................................................................7 
Biostatistician...........................................................................................................................................................7 
Study Coordinators ................................................................................................. Error! Bookmark not defined. 
Research Assistants .................................................................................................................................................7 
PARTICIPATING STUDY SITES .................................................................................................................... 7 
PRÉCIS ..................................................................................................................................................... 8 
LIST OF ABBREVIATIONS ........................................................................................................................... 9 
2. BACKGROUND AND RATIONALE .......................................................................................................... 10 
2.1: Background .................................................................................................................................................... 10 
2.2: Study Rationale ............................................................................................................................................. 11 
3. STUDY DESIGN ................................................................................................................................... 11 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS ................................................................................ 14 
4.1: Inclusion Criteria ........................................................................................................................................... 14 
4.2: Exclusion Criteria ........................................................................................................................................... 14 
4.3: Study Enrollment Procedures....................................................................................................................... 15 
5. STUDY INTERVENTION ........................................................................................................................ 16 
5.1: Intervention, Administration, and Duration ............................................................................................... 16 

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5.2: Concomitant Interventions........................................................................................................................... 16 
5.2.1: Allowed Interventions........................................................................................................................... 16 
5.2.2: Required Interventions ......................................................................................................................... 17 
5.2.3: Prohibited Interventions....................................................................................................................... 17 
5.3: Adherence Assessment................................................................................................................................. 17 
6. STUDY PROCEDURES........................................................................................................................... 17 
6.1: Schedule of Evaluations ................................................................................................................................ 17 
6.2: Description of Evaluations ............................................................................................................................ 17 
6.2.1: Screening Evaluation and Consenting ................................................................................................. 17 
6.2.2: Enrollment, Baseline, and/or Randomization ..................................................................................... 18 
6.2.3: Blinding .................................................................................................................................................. 18 
6.2.4: Study Visits ............................................................................................................................................ 18 
6.2.5: Completion ............................................................................................................................................ 19 
7. SAFETY ASSESSMENTS ........................................................................................................................ 20 
7.1: Specification of Safety Parameters .............................................................................................................. 20 
7.2: Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters .................................. 20 
7.3: Adverse Events (AEs) and Serious Adverse Events (SAEs).......................................................................... 20 
Definitions ........................................................................................................................................................ 20 
Classification of AE Severity ............................................................................................................................ 21 
AE Attribution Scale ......................................................................................................................................... 21 
7.4: Reporting Procedures ................................................................................................................................... 22 
7.5: Follow up for Adverse Events ....................................................................................................................... 22 
7.6: Safety Monitoring ......................................................................................................................................... 22 
8. INTERVENTION DISCONTINUATION ..................................................................................................... 22 
9. STATISTICAL CONSIDERATIONS ........................................................................................................... 23 
9.1: General Design Issues ................................................................................................................................... 23 
9.2: Sample Size and Randomization .................................................................................................................. 24 

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9.3: Definition of Populations .............................................................................................................................. 24 
9.4: Interim Analyses and Stopping Rules........................................................................................................... 24 
9.5: Outcomes....................................................................................................................................................... 24 
9.5.1: Primary Outcome .................................................................................................................................. 24 
9.5.2: Secondary Outcomes ............................................................................................................................ 24 
9.6: Data Analyses ................................................................................................................................................ 24 
10. DATA COLLECTION AND QUALITY ASSURANCE ................................................................................... 25 
10.1: Data Collection Forms:  Data Type & Personnel Collecting Data ............................................................ 25 
10.2: Data Management ...................................................................................................................................... 25 
10.3: Quality Assurance ....................................................................................................................................... 25 
10.3.1: Training ................................................................................................................................................ 25 
10.3.2: Quality Control Committee ................................................................................................................ 26 
10.3.3: Metrics ................................................................................................................................................. 26 
10.3.4: Protocol Deviations ............................................................................................................................. 26 
10.3.5: Monitoring ........................................................................................................................................... 27 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY .................................................................................... 27 
11.1: Institutional Review Board (IRB) Review ................................................................................................... 27 
11.2: Informed Consent Forms ............................................................................................................................ 27 
11.3: Participant Confidentiality.......................................................................................................................... 27 
11.4: Study Discontinuation Understanding....................................................................................................... 28 
12. COMMITTEES ................................................................................................................................... 28 
13. PUBLICATION OF RESEARCH FINDINGS .............................................................................................. 28 
14. REFERENCES ..................................................................................................................................... 28 
15. SUPPLEMENTS/APPENDICES ............................................................................................................. 33 
Appendices List ..................................................................................................................................................... 33 
A. 
Consent Form ......................................................................................................................................... 33 
B. 
Data Collection Forms ............................................................................................................................ 33 

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C.      AE & SAE Forms....................................................................................................................................... 33 
 
 

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STUDY TEAM ROSTER 
Principal Investigator  
Nicholas Wise, PI, Physical Medicine and Rehabilitation, 183 Wing D, C.B.#7200, 170 Manning 
Drive, UNC School of Medicine, Chapel Hill, N.C.  27599-7025.  Phone: 919-966-8865, Fax: 919-
843-5791, email: nicholas_wise@med.unc.edu 
Co-Investigators 
Brian Pietrosimone, Co-I, Department Of Exercise and Sports Science, 26D Fetzer Hall 
University of North Carolina, Chapel Hill, NC 25599. Phone: (919) 962-3617, Fax: (919) 962-0489, 
email: pietrosi@email.unc.edu 
 
Susan Ann Gaylord, Co-I, Department of Physical Medicine and Rehabilitation, 183 Wing D, 
C.B.#7200, 170 Manning Drive, UNC School of Medicine, Chapel Hill, N.C.  27599-7025. Phone: 
919-966-8586, email: gaylords@med.unc.edu 
Jacob Hill, Co-I Department of Physical Medicine and Rehabilitation, 183 Wing D, C.B.#7200, 170 
Manning Drive, UNC School of Medicine, Chapel Hill, N.C.  27599-7025 
Biostatistician 
Mark Weaver, Biostatistician, NC TraCS. 258 Brinkhous-Bullitt Building, CB #7064, Chapel Hill, 
NC 27599. Phone: (919) 843-7680, email: mark_weaver@med.unc.edu 
 
Research Assistants 
 
TBD 
PARTICIPATING STUDY SITES 
Primary Site: EXSS Neurophysiology Lab, Fetzer Hall, University of North Carolina; Chapel Hill, North 
Carolina, 27599. 
Secondary Site: UNC Medical School, Wing D. C.B.#7200, 170 Manning Drive, UNC School of Medicine, 
Chapel Hill, N.C.  27599-7025. 
 
 

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PRÉCIS  
Title: The Effects of Cranial Laser Reflex Technique (CLRT) on Hamstring Flexibility, Strength, and Pain: a 
pilot study. 
Objectives: To assess the acute effect on hamstring flexibility, strength, and pain pressure threshold of a 
novel laser therapy intervention (CLRT) compared to sham.  
Design and Outcomes  
This is a randomized, blinded crossover trial with 44 healthy young adults that will compare the acute 
effects of CLRT to sham laser on hamstring flexibility, strength, and pain pressure threshold (PPT). The 
primary outcome is hamstring flexibility, which will be assessed by independent examiners using the 
standard Knee-Extension-Angle (KEA). As secondary outcomes, hamstring strength will be measured 
using handheld dynamometry (HHD), and PPT with digital algometry. The intervention will consist of 
low-level-laser stimulation of the hamstring cranial reflex points for an average total treatment time of 
30 seconds. A one-week washout period will occur between visits, and participants will have access to 
usual care throughout the research study. The research study will be conducted at the Neurophysiology 
Lab at the University of North Carolina and in UNC Medical School, Wing D. 
 
Specific Aim 1: To examine the acute effect of CLRT on hamstring flexibility as measured by the 
standard 90-90 Knee Extension Angle (KEA) test.  
Hypothesis 1: CLRT will increase mean hamstring flexibility immediately after treatment. 
 
Specific Aim 2: To examine the acute effect of CLRT on hamstring strength as measured by handheld 
dynamometry (HHD). 
Hypothesis 2: CLRT will have a neutral to positive effect on hamstring strength. 
 
Specific Aim 3: To examine the acute effect of CLRT on hamstring pain pressure threshold as measured 
by digital algometry. 
Hypothesis 3: CLRT will increase PPT in the hamstrings. 
 
 
 
 
 
 

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LIST OF ABBREVIATIONS 
ADL 
Activity of Daily Living 
AE 
Adverse Event/Adverse Experience 
ATP 
adenosine triphosphate 
CLRT 
Cranial Laser Reflex Technique 
Co-I 
Co-Investigator 
CRF 
Case Report Form 
CRP 
Cranial Reflex Point 
CTCAE 
Common Terminology Criteria for Adverse Events 
DHHS 
Department of Health and Human Services 
DSMC 
Data and Safety Monitoring Committee 
EXSS 
Exercise and Sport Science 
FDA 
Food and Drug Administration 
HHD 
Handheld Dynamometry 
HIPAA 
Health Insurance Portability and Accountability Act 
Hz 
Hertz 
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption 
IRB 
Insitutional Review Board 
KEA 
Knee extension angle 
LLLT 
Low level laser therapy 
LTrP 
Latent trigger point 
mtNO 
mitochondrial nitric oxide 
mW 
miliwatt 
NC TraCS 
North Carolina Translational and Clinical Sciences Institute 
NIH 
National Institutes of Health 
nm 
nanometer 
NRS 
Numerical Rating Scale 
OHRP 
Office for Human Research Protections 
PBM 
Photobiomodulation 
PI 
Principal Investigator 
PID 
Participant ID 
PPT 
Pain Pressure Threshold 
PS 
Potential subject 
SAE 
Serious Adverse Event/Serious Adverse Experience 
tcPBM 
Transcranial Photobiomodulation 
UNC 
University of North Carolina 
UNC-CH 
University of North Carolina at Chapel Hill 
UP 
Unexpected Problem 
US 
United States 

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2. BACKGROUND AND RATIONALE 
2.1: Background  
Hamstring injuries are a common occurrence in many sports that involve sudden or explosive 
movements, such as jumping and sprinting. Soccer and lacrosse players are especially at risk for these 
frustrating injuries that have the highest rate of recurrence (12-31%) in sports(1) making prevention and 
rehabilitation important areas of study. Static stretching is widely performed, even though it may cause 
a significant loss of strength(2), endurance(3), and explosive performance for 24 hours(4). Latent 
myofascial trigger points (LTrPs) are typically asymptomatic neuromuscular lesions that are associated 
with muscle overload and decreased contractile efficiency and are highly prevalent in the lower 
extremity(5). Currently no clear consensus exists on the most effective protocols for prevention of 
hamstring injuries(6), but decreased flexibility and reduced strength are known risk factors for 
hamstring strain(1) and other musculoskeletal lesions such as lower back pain(7). 
 
Low Level Laser Therapy (LLLT) aka Photobiomodulation (PBM) is the application of low doses of 
monochromatic coherent light from low powered laser devices to induce a biostimulatory effect in the 
target tissue. PBM has been shown to be effective for musculoskeletal pain relief and wound healing(8), 
as well as many other applications (9-14). PBM is anti-inflammatory and reduces oxidative stress, 
working primarily on the mitochondria in stressed or ischemic tissues. The mitochondria produce nitric 
oxide (mtNO) that binds to the chromophore cytochrome c oxidase, competitively displacing oxygen 
leading to oxidative stress and reduced ATP production. Light of suitable wavelength, sufficient 
irradiance and time when applied to injuries is absorbed by cytochrome c oxidase, displacing mtNO and 
thereby reducing oxidative stress and increasing ATP production. A cascade of downstream metabolic 
effects leads to a reduction in inflammatory markers including prostaglandin E2, interleukin 1β, 
interferon (α, β, γ), and tumor necrosis factor-α (15-17). Anti-inflammatory and immune-modulatory 
markers are also upregulated, such as TGF-β1, IL-4, and IL-10 (18, 19). 
Lasers have a long history of use in acupuncture in lieu of needles (20-23). Typically, lower doses (1-4 
J/cm2) of laser light are used on specific points to induce a non-local or systemic effect. Laser 
acupuncture has been shown to be effective in a variety of musculoskeletal conditions such as low back 
pain and knee pain, and has been shown to have significant effects on brain activation in fMRI studies 
(24, 25) 
Cranial Laser Reflex Technique (CLRT) is a novel complementary and alternative (CAM) medicine 
intervention for musculoskeletal conditions that incorporates principles of laser acupuncture with 
chiropractic cranial reflexology(26). Developed in 2006 by Dr. Nick Wise (PI), CLRT has been incorporated 
into clinical practice by hundreds of practitioners around the world. It involves non-invasive laser 
stimulation of a distinct cranial microsystem discovered by chiropractors(27). It was postulated that 
these cranial reflexes are similar in nature to acupuncture points and would likewise respond to 

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photobiomodulation (PBM) from a low level laser (28, 29) (30). Clinical experience by the PI and others 
confirmed that cranial reflexes are indeed responsive to low doses (0.5-5 J/cm2) of laser light: the 
length, strength, and pain in a specific muscle could be improved rapidly, even in cases of chronic post-
stroke muscle spasms(31). This pilot study will examine the acute effect of this promising intervention 
on hamstring flexibility and strength in healthy young adults. 
 
 2.2: Study Rationale 
 
Preliminary Findings  
The Principal Investigator, Dr. Nicholas Wise, has 16 years of clinical experience in conservative care of 
musculoskeletal conditions, specializing in manual manipulation and laser therapy. Since developing 
CLRT in 2006, he has amassed clinical data and presented numerous case reports from clinical practice 
demonstrating that CLRT has the ability to modulate muscle tone, strength, and pain. This is the first 
clinical trial to directly examine these effects of CLRT in human subjects. 
 
Environment and Capabilities of the Research Team 
This project will take place at the University of North Carolina School of Exercise and Sports Science 
Neurophysiology Lab. Dr. Nicholas Wise, the PI of this proposed project, is a board-certified chiropractor 
and postdoc research fellow in the Program on Integrative Medicine in The Department of Physical 
Medicine and Rehabilitation.  
Dr. Pietrosimone is an assistant professor in the Department of Exercise and Sports Science at UNC. His 
research has evaluated the neuromuscular mechanisms related to disability following lower extremity 
joint injury. Additionally, he has sought to develop novel intervention strategies to treat neuromuscular 
impairments and improve clinical outcomes. 
Providing guidance to the project are senior statistician, Dr. Mark Weaver, and Dr. Susan Gaylord, PhD, 
research psychologist and director of PIM, who has expertise in project design and CAM modalities for 
pain management. Jacob Hill is a postdoc researcher in Physical Medicine and Rehabilitation and has 
been trained in the physical assessment tests used in this study. 
3. STUDY DESIGN 
This is a randomized, assessor-blinded, sham controlled crossover study with repeated measures. 
First Visit. The research staff will schedule all study visits in the Neurophysiology Lab or other 
appropriate site in the UNC Healthcare system or medical school. The baseline phase of the first visit will 
include review of inclusion/exclusion criteria and the components of the study. Those who wish to sign 
the consent will complete a brief questionnaire on their activity level, history of hamstring injuries, and 
perceived hamstring tightness. 

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Randomization/Random Allocation. Subjects who meet the inclusion criteria and give consent will be 
randomized to one of the following for the first treatment period: 1) active CLRT; or 2) sham laser.  At 
the first intervention visit, the research assistant will enter the subject’s assigned ID into an online 
computer program (selected by study biostatistician) to determine assignment to one of the two 
periods. The study biostatistician will use computer-generated random numbers to generate the 
allocation sequence using random blocks of random sizes.  The program documents treatment 
assignment in an un-editable form including a date stamp. 
Post Randomization. After randomization, subjects will be asked to complete the three functional 
hamstring tests: KEA, HHD, and PPT. Subjects will have direct contact with the investigator and research 
assistant at each visit to facilitate adverse event reporting.   
Assessments. KEA: The 90-90 Knee Extension Angle test is a functional assessment designed to assess 
lower extremity flexibility and is considered the gold standard for hamstring length (32) The participant 
will be in the supine position on a treatment table. The tested extremity (the right leg in each subject) 
will be placed in a 90° hip and 90° knee position with the contralateral lower extremity placed flat on the 
table. A digital inclinometer will be consistently placed at the level of the medial malleoli and the 
superior pole of the patella. The examiner will maintain 90° of hip flexion. Pelvic position will be 
monitored by palpation of the anterior superior iliac spine and lumbar spinous processes to maintain a 
neutral pelvic position. The examiner will passively extend the knee to the point of a ‘‘strong, but 
tolerable stretch," as reported by the subject. The examiner will read the angle of the inclinometer and 
record the mean value of three attempts. A greater angle indicates greater degree of flexibility. 
 
Hand held Dynamometry (HHD) is currently considered a reliable and valid measurement of peak 
muscle contraction(33). The subject will be prone on the table with right leg bent to 90°. The tester will 
place the dynamometer (microFET2; Hoggan Health Industries, Salt Lake City, UT) at the heel of the 
participant and apply force to the heel, gradually increasing in 3 to 5 seconds. Participants will be 
instructed to resist the applied force and maximally contract the hamstring muscle against the HHD 
device. The test ends once they are no longer able to resist the force and the leg begins to move (break 
point). The investigator will record the mean value of three attempts. 
 
Pain Pressure Threshold (PPT) is a reliable, accurate and valid method for measuring muscle pain 
sensitivity and response to treatment(34). The digital algometer (FDX, Wagner Instruments, Greenwich, 
CT) is a hand-held muscle tester with a range of 0–100 lbf that consists of a padded disc with a diameter 
of 0.5” attached to a microprocessor-control unit that measures peak force (pounds or kilograms). The 
unit has a digital readout for peak-applied pressure and provides a built-in calibration routine that 
verifies a valid calibration. In order to determine PPT, the researcher will apply the tip of the algometer 
to a tender spot in the participant’s hamstrings and increase the amount of pressure until the 
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the algometer is removed and the peak force 
recorded. The mean of three repeated measures 
will be reported. 
 
Intervention: CLRT. Subject will don protective 
eyewear and remain in the prone position. The 
hamstring reflexes are two lines on the posterior 
portion of the top of the head, approximately 2 cm 
long and 2 cm apart, running parallel to the sagittal 
suture (fig. 1). The posterior end of the reflexes 
can be located by finding the vertex, or CZ point in 
the standardized 10-20 EEG system, and moving 
laterally approximately 1 cm. 
Sequence:  
The aperture of the laser probe will be placed at 
point (a), turned on and moved to point (b) at a 
speed of approximately 2 cm/s. The laser will be 
turned off and quickly returned to point (a), turned 
on and moved to point (b) again. This will be 
repeated for a total of 30 times. The probe will 
make light contact with the scalp during the powered laser pass, moving aside as much hair as possible.  
Device: The treatment device to be used in this study is a Class IIIB 810nm 200mW near-infrared GAAlAS 
diode laser (THOR Photomedicine Ltd, Great Britain) that is currently marketed in the US. The laser 
probe is FDA-cleared and classified as a non-significant risk device. The spot size is 0.0364 cm2, and the 
treatment time is 30 seconds. Current best-practice recommendations for laser acupuncture(35) 
recommend a dosage between 1-4 J/cm2 per point. Since the cranial reflex point (CRP) is a line of 2 cm, 
for the purposes of calculating dosage, we will treat it as a series of 10 connected points each with a 
diameter of 2mm. With the scanning rate of 2cm/s, each “point” on the line will receive 1/10 of each 
pass, totaling 3s (out of 30s total) exposure time per point. The dose per point for this intervention is 
calculated to be approximately 1.65 J/cm2. 
𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 ൬𝐽𝐽
𝑐𝑐𝑐𝑐2൰= 
𝑒𝑒𝑒𝑒𝑒𝑒 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝(𝑊𝑊) ∗𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 (𝑠𝑠) ∗𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒 𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 (
1
𝑐𝑐𝑐𝑐)
𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 (𝑐𝑐𝑐𝑐2)
 
= 0.2 𝑊𝑊∗3𝑠𝑠∗1
0.0364 𝑐𝑐𝑐𝑐2 = 1.65 
𝐽𝐽
𝑐𝑐𝑐𝑐2 
Random Allocation. At the first intervention visit, the research assistant will enter the subject’s assigned 
ID into an online computer program that will determine assignment to one of the two treatment 
periods. Using a random number sequence to generate a permuted block of 2-4, the program ensures 

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equal numbers of subjects in each arm.  The program documents treatment assignment in an un-
editable form including a date stamp. 
Masking. The research coordinator and treating investigator will be unmasked. All research assistants 
performing the assessments will be masked.  Masking will be maintained in the random allocation 
procedure. The treating investigator will not indicate to subjects or assessor to which period the 
participant is assigned. 
Remuneration. Subjects will receive an Amazon gift card worth $25 upon completion of the second visit. 
If the subject completes only the first visit, they will be compensated a prorated amount with a card 
worth $15. 
The following patient-reported variables will be assessed: 
1) Expectation of benefit: Measured with a modified Borkovec and Nau scale(36). This instrument 
provides an assessment of credibility of each intervention using an adaptation of a validated 
credibility scale previously developed for psychological studies for purposes of comparing the 
two treatment arms. This instrument has been successfully adapted for use in other conditions 
such as chronic pain and migraine headache. It will be administered after each subject 
completes the second visit. 
2) Perceived value of the intervention is measured at the end of the active intervention via 
questionnaire.  At the end of the post-intervention phase, subjects will be invited to participate 
in a brief post-study interview to assess their overall impressions of the treatment. 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1: Inclusion Criteria 
Participants must meet all of the inclusion criteria to participate in this study. Criteria include:  
1) Between 18-35 years of age  
2) All genders 
3) Willing to complete two study visits over 2-3 weeks 
4) Able to read and communicate in English 
4.2: Exclusion Criteria 
All candidates meeting any of the exclusion criteria at baseline will be excluded from study participation. 
Exclusion criteria include:  
1) Current lower back condition with pain, numbness or tingling that radiates down the legs  
2) Active treatment for a major medical illness, such as heart disease, uncontrolled diabetes or 
hypertension, malignancy, autoimmune, or immune deficiency disorder 

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3) History of vasculitis, intracranial mass, clotting disorder (including medication-induced, e.g., 
warfarin) 
4) Current skin malignancy on scalp 
5) Cognitive dysfunction preventing informed consent 
6) Pending or currently receiving benefits from personal injury litigation, including worker’s 
compensation 
7) Chronic long-term disability related to lumbosacral injury/symptoms 
8) Epilepsy 
4.3: Study Enrollment Procedures  
Sample Size and Population  
Target Population. The target population will be healthy young adults between the ages of 18-35.  
Healthy young adults are chosen as the target population because this is a) a pilot study and b) the 
expectation of rapid subject recruitment and excellent retention. 
Recruitment Estimates. Approximately 60 healthy young adults will be screened to achieve a pre-
intervention sample size of 44 subjects. We expect at least 38 of the 44 to complete the 2-week 
intervention, which will provide adequate power to test Aim 1.  
Sources of Subjects 
The primary source for recruitment will occur through the Exercise and Sports Science Department. 
Additional recruitment for potential subjects will occur at other sites around UNC. The study will be 
listed on the NC TraCS research recruitment website www.jointheconquest.com. 
Consenting  
All subjects will be assessed for eligibility on the basis of their medical condition by the PI, Dr. Wise, a 
board certified chiropractor specializing in conservative care of musculoskeletal conditions. Interested 
individuals will sign a permission to contact form.  Prior to the initial visit with a study team member, the 
subject will complete a telephone screen with telephone consenting. If the potential participant remains 
eligible, a study team member will schedule an appointment for the first study visit. 
Consenting Process 
Informed consent forms (ICFs) will be reviewed with the patient by either the study coordinator, the 
project supervisor, or the co-investigator. The study team member will read the ICFs to the patient as 
they follow along. Any questions the patient may have will be answered accordingly. After reviewing the 
consent, a patient may decline to participate, sign to participate at the time of the meeting, or take the 
ICFs home with them to be signed at a later time. The patient will be considered to be a subject at the 
time of signing the consent. Persons who cannot sign for themselves will not be recruited.  
Documentation 

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Documentation of each study visit will include a visit checklist signed by the study team personnel 
completing the visit. 
Randomization  
The study coordinator randomizes eligible subjects into one of the two arms at the time of their first 
visit using a computer-generated blocked randomization process. Please see Section 9.2 for details.   
5. STUDY INTERVENTION  
5.1: Intervention, Administration, and Duration  
CLRT is a complementary or alternative intervention that incorporates principles of laser acupuncture 
with chiropractic cranial reflexology. Instead of acupuncture points derived from TCM, CLRT involves low 
level laser stimulation of two distinct cranial microsystems discovered by chiropractors. The first map of 
cranial reflex points/pathways (CRP) was originally discovered by a doctor named Jack Elvidge using 
Applied Kinesiology, and each CRP corresponds to a major muscle or group. These soft-tissue CRPs are 
either points or directional lines on the skull, and they appear to have an influence on the particular 
muscle’s tonus and strength. It was originally found that stimulating a linear reflex with digital pressure 
in one direction relaxed the muscle’s tone, and stimulating it in the opposite direction increased the 
tonicity.  
The second set of CRPs used in CLRT were discovered by David Denton, D.C., and consists of points that 
relate to each vertebra of the spine, rib, sacroiliac joint, sacrum and coccyx. Denton found that subtle 
manipulations of these points affected the position and function of misaligned vertebra in manner 
similar to adjusting them directly. Dr. Nicholas Wise developed CLRT after postulating that the CRP’s had 
similar optical properties to the acupuncture meridians, and would respond to coherent light in a similar 
manner. Upon clinical experimentation, he found that the cranial reflexes were in fact extremely 
responsive to low doses of laser light. The major goal of CLRT is to quickly decrease in pain, increase 
joint range of motion, and achieve lasting functional improvements. CLRT can be performed with a 
range of laser powers from 5milliwatts (mW) to 500mW with similar results, and wavelengths from 
405nm-840nm have been used successfully. 
The first visit will last approximately 1 hour and the second visit will take 30 minutes. 
5.2: Concomitant Interventions  
5.2.1: Allowed Interventions   
Subjects will be allowed to partake in their usual exercise and physical activities.  

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5.2.2: Required Interventions   
Participation in both study arms of the crossover trial.   
5.2.3: Prohibited Interventions  
None. 
5.3: Adherence Assessment  
We will define study adherence as completion of both study visits.   
6. STUDY PROCEDURES  
6.1: Schedule of Evaluations 
Activity 
Visit 1 (Week 1) 
Visit  2  
 (Week 2) 
Check-in 
Call 
(Week 3) 
People involved in visit/activity: 
Study Coordinator, 
Investigator and 
Research Assistant 
Investigator 
and Research 
Assistant 
Research 
Assistant 
Location: 
Neurophysiology Lab 
NL 
Phone 
Eligibility Criteria Review 
X 
 
 
Informed Consent Review   
X 
 
 
Randomization 
X 
 
 
Musculoskeletal History 
X 
 
 
Hamstring Tightness Questionnaires 
X 
X 
 
90-90 KEA 
X 
X 
 
Handheld Dynamometry 
X 
X 
 
Intervention 
X 
X 
 
Expectation of Benefit 
X 
 
 
Perceived value of the intervention 
 
X 
 
Follow up 
 
 
X 
6.2: Description of Evaluations  
6.2.1: Screening Evaluation and Consenting 
Screening  
A brief telephone call by the research assistant that will cover inclusion/exclusion criteria and 
components of the study will be completed. If subject is interested, they will be invited to consent and 
enroll in the study. 
Consenting 
Interested participants will travel to UNC Neurophysiology Lab at Fetzer Hall to meet with a Study 
Coordinator or Research Assistant to review consent forms and sign and date (in a private room).  

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After participants sign the consent, their musculoskeletal history questionnaire will be reviewed by the 
PI to ensure that the patient has no outlying medical issues that would exclude participation. 
6.2.2: Enrollment, Baseline, and/or Randomization 
Enrollment 
Subjects are enrolled at time of signing the consent form. The analysis will be done under an 
Intention to Treat. 
Baseline Assessments 
Age, gender, hamstring injury questionnaire, perceived hamstring tightness scale, activity level. 
  
Randomization 
Randomization occurs at the end of the baseline and screening phase immediately prior to 
starting the intervention.    
6.2.3: Blinding 
Subjects and assessors will be blinded to treatment allocation. The subject will be face down, eyes 
closed, and wearing protective eyewear that blocks the specific wavelength of the laser light 
during the intervention. 
Individuals authorized to break the blind include the PI and study statistician. 
Circumstances for breaking the blind include the development of a Serious Adverse Event (SAE) or 
recurrent Adverse Event (AE) apparently related to the research interventions. 
The procedure for breaking the blind is to have the research assistant inform the PI or the study 
statistician of the allocation of the subject. 
After each treatment session, the participants will complete a de-blinding questionnaire 
administrated by the assessor providing a dichotomous ‘yes’ or ‘no’ answer as to whether active 
treatment was received. This response will be followed by a second question regarding how 
certain they were that active treatment was received on a 0–10 numeric rating scale (NRS), where 
0 represents absolutely uncertain and 10 represents absolutely certain. 
6.2.4: Study Visits 
Study visits will ideally be one week apart. (See Section 6.1 for Schedule of Evaluations table.) 
• Visit 1:  
 
o Inclusion / Exclusion Criteria  
o Consenting:  Subject Enrollment  
o Study questionnaires:  Hamstring Injury questionnaire 
o Randomization  
o KEA 

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o HHD 
o PPT 
o Intervention 
o Post KEA 
o Post HHD 
o Post PPT 
o De-blinding questionnaire 
 
• Visit 2: Week 2-3 
o KEA 
o HHD 
o PPT 
o Intervention 
o Post KEA 
o Post HHD 
o Post PPT 
o De-blinding questionnaire 
 
6.2.5: Completion 
• 
Study questionnaires:   
o Expectation of benefit/ Believability scale 
• 
Evaluation for participants who discontinue study intervention early 
Potential reasons for early termination include: subject no longer interested, adverse 
events, subject not able or willing to follow the protocol, subject moved away from the area 
or prolonged travel.   
If subjects withdraw early, the PI or his designee will attempt to follow-up by telephone to 
inquire about health status as it relates to adverse events experienced by the subject 
leading to early discontinuation of participation.  

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7. SAFETY ASSESSMENTS  
7.1: Specification of Safety Parameters 
Low level laser devices used for the purposes of photobiomodulation or acupuncture are designated by 
the FDA as “non-significant risk” devices (37). After four decades of research, over 4000 peer-reviewed 
papers and over 150 Phase III clinical trials, there are no known side effects attached to low level laser 
therapy (LLLT). Animal studies have shown that lasering the head, or transcranial photobiomodulation 
(tcPBM), is very safe and causes no thermal or neoplastic changes in the cortex(38). The use of tcPBM 
has been shown to have promise for treating traumatic brain injury(39-41) and stroke(42-44), as well as 
enhancing mood(45-47) and cognition(48-52) in humans.  
 
CLRT involves principles and laser dosages very similar to laser acupuncture. Laser acupuncture has been 
extensively studied and deemed to be safe and effective for certain musculoskeletal conditions(21), 
especially in long-term follow up (29). No known or anticipated serious side effects from CLRT have yet 
occurred but minor reactions may include mild delayed onset muscle soreness or headache. Due to the 
intensity of the laser light, subjects will wear proper eye protection that blocks the specific wavelength 
of light while lasers are in use.  
 
Based on previous research, no serious side effects are anticipated. The PI will closely monitor all 
subjects for any adverse events and will report them to the IRB if any arise. 
 
Examples of safety measures include: monitoring subjects for any discomfort related to intervention; 
reports of cramps, spasms, headache or delayed onset muscle soreness.  
7.2: Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
1) Timing: each contact with the subject will be an opportunity to inquire about adverse events.  
2) Recording: each incidence of an adverse event will be recorded in the case report form in a 
designated location for this information.  
3) Analyzing: the PI will be informed of all adverse events and will forward the information to the 
IRB. 
7.3: Adverse Events (AEs) and Serious Adverse Events (SAEs) 
Definitions 
An adverse event (AE) is any untoward medical occurrence in a subject during participation in the clinical 
study. An adverse event can include a sign, symptom, abnormal assessment (laboratory test value, vital 
signs, electrocardiogram finding, etc.), or any combination of these. 
A serious adverse event (SAE) is any AE that results in one or more of the following outcomes: 

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• 
Death 
• 
A life-threatening event 
• 
Inpatient hospitalization or prolongation of existing hospitalization  
• 
A persistent or significant disability/incapacity 
• 
A congenital anomaly or birth defect 
• 
An important medical event based upon appropriate medical judgment 
Classification of AE Severity 
Classification of AEs will be based on the Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4, 2009. AEs will be described by symptom or condition/diagnosis, and graded for severity (mild, 
moderate, or severe), depending on the intensity of the event.  Two additional categories will be used 
based on the CTCAE system, “life threatening” and “death”.  
Grade 1.  Mild: asymptomatic or mild symptoms; clinical or diagnostic observations only; 
minimal impact on subject’s life; intervention not indicated.  
Grade 2. Moderate: medical care sought; significant but limited inconvenience on Activities of 
Daily Living (ADL) or lifestyle; local or noninvasive intervention indicated. 
Grade 3. Severe: medically significant but not immediately life-threatening; disabling; limiting 
self-care; substantial disruption to the subject’s well-being; hospitalization or prolongation of 
hospitalization indicated. 
Grade 4. SAE. Life-threatening consequences; urgent medical intervention indicated.  
Grade 5. SAE. Death: related to AE.  
An AE that is graded as severe (Grade 3) can be distinct from an SAE (Grades 4 and 5). A subject 
could experience a severe AE (Grade 3) that does not meet the definition of an SAE (see above). 
Alternatively, a subject could experience a moderate AE (fever, mild confusion) that meets the 
SAE definition (example - need for antibiotics to combat a life threatening infection).  
AE Attribution Scale  
AEs will also be classified on an assessment of relatedness to the study intervention. AEs will be 
categorized according to the likelihood that they are related to the study intervention. They will be 
labeled as: 1) definitely related, 2) definitely unrelated, 3) probably related, or 4) possibly related to the 
study intervention in the opinion of the PI after review of the circumstances and relevant records. 
Attributions will be made by the PI. 

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7.4: Reporting Procedures 
Those events that will be asked about (solicited) include: delayed onset muscle soreness and pain in the 
hamstring. Other events that could occur with maximal contraction of the hamstring strength test 
include fatigue, cramps, spasms, muscle strain, or muscle pain.  
Unsolicited events will be captured by query at each visit after enrollment. 
Time frames for reporting and collecting AEs are weekly. Reporting of AEs must be to the IRB and OHRE. 
For SAEs the time frame is daily reporting and capture as soon as possible. 
Detection of AEs and SAEs will be the responsibility of each member of the research team at every 
subject contact. Reporting procedures for unexpected events related to the study intervention will 
include written documentation of the finding or complaint, which will occur within 5 days for AEs and 
immediately or as soon as possible for SAEs. The goal of reporting is to inform the PI for a determination 
of severity, relatedness to the research, and next level of reporting, i.e. IRB, TraCS Institute. 
Decisions regarding relatedness and severity will be made by the PI once all available information has 
been reviewed. 
Safety Monitor members will be informed of AEs and SAEs as part of their routine reviews. 
Case Report Forms will be used to collect AE and SAE data entered into a secure database. 
Reports will be distributed to the PI and Co-I’s and Project Manager. These reports will be coded and 
without identifiers. 
7.5: Follow up for Adverse Events 
Subjects who have experienced AEs will be followed until resolved or considered stable by the PI.  For 
issues not resolved, a minimum period of follow up is 1 month with contact on a weekly basis by 
telephone or in person.  
7.6: Safety Monitoring  
The senior advisors on this study will serve as data and safety monitors and make up the Data and Safety 
Committee: Dr. Brian Pietrosimone, Dr. Susan Gaylord, and Dr. Mark Weaver. We will record all adverse 
events and unexpected health problems and review weekly with the study team. Safety monitors will 
review the adverse events and unexpected health problems after the tenth subject reaches visit 2 in the 
intervention and every 3 months thereafter.  
8. INTERVENTION DISCONTINUATION  
Discontinuation of intervention for a participant: Subject may stop their participation for any reason, 
e.g., the subject is non-compliant with the protocol; subject develops unacceptable side effects; or 
psychosocial circumstances prevent continuation.    

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Possible reasons for discontinuation of the whole study:  Study closure by NC TraCS; research 
environment is no longer supportive; multiple Unexpected Problems (UP); insufficient recruitment to 
answer research hypotheses.  If greater than 3 enrolled and randomized subjects develop a grade 3 or 
greater adverse event due to the intervention, the entire study would be stopped and the safety 
monitors would reevaluate. 
Early discontinuation: Participants will continue to be followed, with their permission, for another 6 
weeks if study interventions are discontinued for reasons other than the normal end of the study.  
Normal end to the study: Subjects completing the final evaluation will be followed up one week after 
the final visit by phone call to solicit any possible AEs. 
9. STATISTICAL CONSIDERATIONS  
9.1: General Design Issues  
 
Primary Outcome 
90-90 Knee Extension Angle Test.  KEA is a functional test designed to assess lower extremity flexibility 
and is considered the gold standard test for assessing hamstring length (53).  Results will be recorded as 
degrees of knee flexion angle. A clinically significant effect size is an increase of 5 degrees. 
 
Secondary Outcomes 
Handheld Dynamometry. HHD is currently considered a reliable and valid measurement of peak muscle 
contraction. The subject will be prone on the table with right leg bent to 90° and will maximally contract 
the hamstring muscle for 4-5 seconds against the HHD device. The investigator will record the mean 
value of three attempts. 
 
Pain Pressure Threshold. PPT is a reliable, accurate and valid method for measuring muscle pain 
sensitivity and response to treatment(54). In order to determine PPT, the researcher will apply the tip of 
the algometer to a tender spot in the participant’s hamstrings and increase the amount of pressure until 
the participant verbally informs the researcher when the sensation of pressure became pain. At this 
point the algometer is removed and the peak force recorded. The mean of three repeated measures will 
be reported. An increase in PPT signifies an increase in pain tolerance. 
 
Additional Variables  
Age, gender, activity level, perceived hamstring tightness, perceived hamstring flexibility and 
perceived hamstring strength will be assessed at baseline and subsequent follow up visit.  

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9.2: Sample Size and Randomization 
 
Sample Size and Power:  Based on previously published results(55), we would consider a mean increase 
of 5º on the KEA (e.g., from 135º to 140º) to be clinically meaningful, and we assume a common 
standard deviation of 15º.  We further assume that correlation between repeated measurements from 
the same individual will be at least 0.75 (likely a conservative assumption).  Under these assumptions, 
enrolling 38 participants would provide at least 80% power using a two-sided test at the 0.05 level.  
Allowing for up to 10% loss to follow-up, we will enroll 44 participants.  
9.3: Definition of Populations 
We are defining our intention-to-treat population as all subjects who are randomized. We will retain 
randomized subjects into the treatment periods to which they were assigned. For a per-protocol analysis 
(if necessary), we will analyze data from subjects who attend and complete both study visits. 
9.4: Interim Analyses and Stopping Rules 
We are not planning any pre-specified interim analyses for any reason. The study may be suspended by 
our PI or the Data and Safety Monitoring Committee (DSMC) if a severe adverse event occurs that is 
deemed to be secondary to the intervention. The DSMC may also suspend or stop the study or a study 
arm if reported adverse events are increasing, either across intervention arms or in a particular study 
arm.   
9.5: Outcomes  
Outcomes include two functional measures that will be logged into REDCap at the time of the 
evaluation. The study coordinator will verify complete data entry after each study visit.  
9.5.1: Primary Outcome  
We define the primary outcome as the change in angle of the KEA test from the time before 
to the intervention to afterwards.  
9.5.2: Secondary Outcomes   
We define the secondary outcome as the difference in peak hamstring strength on HHD, and 
difference in PPT scores between pre and post-intervention time periods. 
Subgroup analyses:  conduct analyses on the primary outcome stratifying on gender and 
baseline hamstring subjective tightness, flexibility and strength, number of prior 
hamstring injuries.  
9.6: Data Analyses  
 

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To compare mean KEA response between treatment conditions, we will use a linear mixed effect model.  
The model will include fixed effects for treatment, period, and baseline pre-intervention KEA within each 
period. The model will include random subject effects to account for correlation between repeated 
measurements. Given the length of the washout period relative to the treatment period, the primary 
analysis will assume no carry-over effects and will estimate effect size along with a 95% confidence 
interval. As a secondary analysis to explore the potential for carry-over, we will include and test a fixed 
effect for treatment-by-period interaction. If significant carry-over is identified, we will also report 
comparisons using only the period 1 data. We will use a similar approach to explore intervention effects 
on HHD and PPT. 
 
10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1: Data Collection Forms:  Data Type & Personnel Collecting Data  
 
Principal Investigator—Nicholas Wise 
Co-Investigator- Jacob Hill 
Research Assistants—TBD 
 
Data Collection and Contacts with Subjects.  
Paper records collected at study visits will be entered into the REDCap database, a secure online 
research database system. Paper source documents will be locked in a file cabinet under the control of 
the full-time Study Coordinator.   
10.2: Data Management  
All data will be collected at the University of North Carolina at Chapel Hill. Online questionnaires will be 
completed by subjects during study visits. Data collection forms are listed in Table 5 and are attached to 
this document in appendices.  
The research assistant or investigator will verify questionnaire completion after each study visit; data 
will be input by research assistants. Source documents are identified by a Study Identification (ID). 
Investigator will compile a data completion report every other month to be reviewed at study meetings.  
10.3: Quality Assurance  
10.3.1: Training  
Current HIPAA and CITI Human Ethics training certificates or their equivalents are required of all 
study personnel who will be collecting, entering or managing data. 
Before participant data is collected, the PI or Project Manager will ensure that staff has completed 

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training for applicable tasks. A log including dates and type of training will be kept in the Study 
Regulatory Binder. 
The Study Manual of Operating Procedures (MOP) will include detailed procedures for each of the 
following: 
1. Consent forms 
2. Functional assessment tests (KEA, HHD, PPT) 
REDcap will be used to track recruitment data, questionnaires, and initial and post-intervention 
evaluations. 
The PI will train staff in data entry procedures and report generating options in REDcap database as 
outlined in the Study MOP. 
10.3.2: Quality Control Committee  
Quality control will be an agenda item of the research meeting which will include the PI, Research 
Assistants, and Co-Is as available. 
Data will be presented in the meeting from information gathered as described in section 10.3.3 
below. 
10.3.3: Metrics 
Outcome Measures: 
Questionnaires designed to be completed on paper (Expectation of Benefit / Credibility survey) will 
be collected and entered into the REDCap database by a research assistant. The research assistants, 
under supervision of the PI, will also enter study visit data, including KEA, HHD and PPT scores. The 
research assistant who will be responsible for data entry will not have contact with enrolled study 
participants. Double data entry for all paper-based outcome measures will be performed. 
Corrections will be made using source documents. If a greater than 1% discrepancy in data is found, 
then additional training will take place.  
10.3.4: Protocol Deviations 
Staff will be trained to record any protocol deviation that may occur while performing their specific 
research related activities. Many of the data collection forms include comment sections where 
protocol deviation information will be captured on the source documents. Deviations will also be 
documented in REDcap. Training of the research staff will include practices of double checking all 
demographics, inclusion/exclusion criteria, data collection procedures including capture and secure 
storage, intervention procedures and data management activities.   
Deviations will be documented as a written report submitted to the UNC IRB by the PI or Project 
Manager or Study Coordinator within 2 weeks. If warranted, corrective action plans will be 

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developed and submitted to the IRB as part of that reporting process.  
10.3.5: Monitoring 
Outside monitoring of the study is not required.  However, the Regulatory binder will be maintained 
as if study monitoring were to take place. 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1: Institutional Review Board (IRB) Review  
This protocol and the informed consent documents and any subsequent modifications will be reviewed 
and approved by the IRB and the Scientific Review Committee responsible for oversight of research at 
UNC. The IRB application, modification, and renewal procedures will be adhered to throughout the 
study.    
11.2: Informed Consent Forms 
A signed consent form will be obtained from each participant.  
The consent form will describe the purpose of the study, the procedures to be followed, reasons not to 
be in the study, risks and benefits of participation, responsibilities of the participant, incentives and 
remunerations, privacy and confidentiality measures, and names and contact information for the PI and 
the study staff.  
Procedures for obtaining and documenting informed consent: Interested persons meeting screening 
criteria of age, inclusion / exclusion will be given a copy of the informed consent form (ICF) in the 
presence of the Study Coordinator or their designee, who will then read the consent orally with the 
potential subject (PS), indicating important points in each section and answering any questions at that 
time. The PS will be given time to re-read any or all of the form, and they may take it home for further 
review if they so desire for signing at a later time. If they have their questions answered and are willing 
to participate, the informed consent will be signed at the time of the meeting by the PS and research 
team member obtaining the consent. The PS is considered to be a subject in the study (enrolled) at the 
time of the signing. A copy of the IFC will be given to each participant.  
Those below age 18, pregnant women, prisoners, and those requiring a legally authorized 
representative are excluded from participation.  
11.3: Participant Confidentiality  
Participant confidentiality will be maintained according to the Health Insurance Portability and 
Accountability Act (HIPAA).  
Any data, forms, reports, and other records that leave the site will be identified only by a participant 

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identification number (Participant ID, PID) to maintain confidentiality.  
All records will be kept in a locked file cabinet in Medical School Wing D. All computer entry and 
networking programs will be done using PIDs only. Information will not be released without written 
permission of the participant, except as necessary for monitoring by IRB, the FDA, and the OHRP. 
Research records arising from this study will be retained at a secure UNC-maintained locked site for 5 
years with access limited to the PI and named designees. 
 
11.4: Study Discontinuation Understanding 
The study may be discontinued at any time by the IRB, the OHRP, the FDA, or other government 
agencies as part of their duties to ensure that research participants are protected.  
12. COMMITTEES 
Data and Safety Monitoring Committee. No other committees.    
13. PUBLICATION OF RESEARCH FINDINGS  
Any presentation, abstract, or manuscript will be made available for review by NC TraCS prior to 
submission. Publication Committee formation will be contingent on successful data collection.  
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15. SUPPLEMENTS/APPENDICES 
Appendices List 
A. Consent Form 
B. Data Collection Forms 
B.a  IPAQ Activity Questionnaire 
B.b  Hamstring History 
B.c  De-blinding Form 
B.d  Expectation of Benefit / Credibility 
     C.      AE & SAE Forms 
 
 
 
 

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Appendix A: Consent Form

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Appendix A (cont.): Consent Form

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Appendix A (cont.): Consent Form 

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Appendix A (cont.): Consent Form 

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Appendix A (cont.): Consent Form 

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Appendix B(a): IPAQ (version 1.0) 

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Appendix B(a) cont.: IPAQ (version 1.0) 

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Appendix B(b): Hamstring History (version 1.0) 

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Appendix B.c: De-blinding Questionnaire (Ver. 0.1)

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Appendix C.a: Adverse Event Form (version 1.0) 

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Appendix C.b: Serious Adverse Event Form (version 1.0)

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Appendix C.b (cont.): Serious Adverse Event Form (version 1.0)
 
 
 
 
 
 

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Appendix C.c : Modified Borkovec and Nau Expectation of Benefit/ Credibility Form (version 1.0) 

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