Can Transcranial Direct Current Stimulation Improve Ambulation and Fatigue Resistance in People With MS?
Phase: NA
Conditions: Multiple Sclerosis
Sponsor: Colorado State University

IRB Approved Protocol, Consent and Statistical Plan :  
Title: Can transcranial direct current stimulation improve ambulation and fatigue resistance in 
people with MS? 
NCT #: NCT02987621 
Document date: 08/24/2017 

 
PROTOCOL
Biomedical
Colorado State
University
Protocol # 16-6856H
 Date Printed: 07/18/2018
Continuing review
1
Personnel Information
3
Subject Population
4
Study Location
5
General Checklist
5
Funding
6
Expedited Paragraphs
7
Purpose,Study Procedures,Background
8
Radioisotopes or Radiation Machines
12
Medical Equipment for Human Subjects and Laboratory Animals; Investigatiional Devices
13
Drugs, Reagents, or Chemicals
13
Subject Population (a-g)
13
Subject Population (h-m)
14
Risks
15
Benefits, Procedures to Maintain Confidentiality
18
Potential Conflict of Interest
19
Informed Consent
20
Assent Background
20
HIPAA
21
Attachments
22

 
PROTOCOL
Biomedical
Colorado State
University
Protocol # 16-6856H
 Date Printed: 07/18/2018
Obligations
24
Event History
25

Page 1 of 25
 
1
PROTOCOL
Biomedical
Colorado State
University
Protocol # 16-6856H
 Date Printed: 07/18/2018
Protocol Title:
Can transcranial direct current stimulation improve ambulation and fatigue resistance in
people with MS?
Protocol Type:
Biomedical
Date Submitted:
08/24/2017
Approval Period:
09/15/2017-09/14/2018
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
* * * Continuing review * * *
 
To renew your protocol: 1. Complete this one-page form; 2.  If necessary, update any sections of the protocol
that need to be updated for the upcoming year (e.g., change in personnel, location); 3. Electronically "sign" the
application by clicking in the check box on the bottom of the "Obligations" page; 4.  Remember to click "Submit
Form" and confirm your intent to submit by clicking "OK" so that the IRB administrators receive your application.
You must answer each question. Input N/A to answer any questions that are not applicable.  NOTE:  Documents
that contain much of the information required to answer the participant number questions below can be found in
the "Event History" section of each protocol.  The status on your homepage will be "Submitted to IRB" when your
submission is successful. IMPORTANT:   If the Department Head has changed since your last approval, please
be sure to update the Department Head listing on the personnel Information screen of your protocol.
 
1.
Summary: Number of Participants Associated with the Protocol: 
 
  
  
 a. 
Total number of participants approved to date:
40 (20 strength and 20 fatigue)
 
  
  
 b. 
Number of participants studied since the last approval date:
5 (1 strength and 4 fatigue)
 
  
  
 c. 
Total number of participants studied since the beginning of the project:
5 (1 strength and 4 fatigue)
 
  
  
 d. 
Number of participants remaining to study (total number of participants approved  LESS  the
total number of participants studied to date):
35
 
  
  
 e. 
Please explain if there is a discrepancy in participant numbers (e.g., more participants
responded to a survey than had been approved):
n/a
 
 
2.
 a. 
Reasons and number of withdrawals from the research (both subject and investigator initiated)
since the last approval date.
none

Page 2 of 25
 
 
  
  
 b. 
Number of subjects lost to follow-up since the beginning of the study.
none
 
  
  
 c. 
Please summarize any protocol deviations/violations or unanticipated problems (UPs)/adverse
events (AEs) since the last continuing review or original approval (if this is your first continuing
review).  Please indicate if any of the unanticipated problems/events are being reported to the
IRB for the first time.  If you have or will make changes to your protocol as a result of any
unanticipated problem/event or adverse event, please summarize those changes in Question #5
below.
none
 
 
  
  
 e. 
Complaints about the research during the last year.
none
 
3.
A summary of any recent findings, literature, or other relevant information (especially pertaining to
risks), if applicable.
none
 
4.
Description of the remainder of project:
Y
Do you plan to recruit more subjects?
 
If "No," have all subjects completed all research-related interventions?  Note: Protocols must be
renewed to continue recruiting participants and/or collect data from already recruited participants.
 
N
Are you only performing data analysis?  NOTE:  If you are analyzing data with no identifiers (i.e., you
cannot link your data to individuals), you can close your protocol by submitting a Final Report.
 
N
Does this protocol have a Data Satety Monitoring Board (DSMB)?
 
If you do have a DSMB, have reports been submitted to the IRB and/or the Sponsor?
Upload any DSMB reports that have not yet been submitted to the IRB since the approval
or last continuing review.
 
5.
Summarize all approved changes in the protocol since the last continuing review or since the original
approval (if this is your first continuing review).  For example: Have you amended your protocol
during the past year?  Are you requesting to make any changes for the upcoming year?  Have you
included any changes as a result of an unanticipated problem/event or Adverse events (AE)?  Have
there been any personnel changes in the past year (including a change in department head)?
Amendment 1: Added clinicialtrials.gov language to the consent
Amendment 2: Removed the requirement of physician clearance and updated screener to mimic
other tDCS protocol
Amendment 3: Add compensation for fatigue group and the strength group was closed to
enrollment.  Please note: the investigator would like to keep the strength group open to enrollment,
please revise in the next approval letter.
 
         
If necessary, proceed to the appropriate section(s) of the protocol and make your requested changes.
Remember that if you are requesting to revise a document that is already attached, you must delete the
already attached document and upload the revised document.
 

Page 3 of 25
 
6.  
List of Protocol Sections (and questions) that have been changed/modified.
Updated Felix Proessl's personnel status
Please note: the investigator would like to keep the strength group open to enrollment, please revise
in the approval letter.
---------------------------------------------------------------------------------------------
* * * Personnel Information * * *
IMPORTANT NOTE: Mandatory Personnel on a protocol are: Principal Investigator and Department Head. Only
the Principal Investigator can submit the protocol; although other personnel listed on the protocol can create the
protocol. Human Subjects Protection Training is mandatory for Principal Investigator, Co-Principal Investigator,
and Key Personnel (as defined by NIH). Training must be updated every three (3) years.
 
Principal Investigator  Mandatory
Name of Principal Investigator
(Faculty, Staff or Postdoc)
Degree
Title
Rudroff, Thorsten
Assistant Professor
Email
Phone
Fax
Thorsten.Rudroff@colostate.edu
(970) 491-8655
Department Name
Campus Delivery Code
 
1582 Dept Hlth & Exer Sci
 
 Human Subjects Training Completed? PIs must complete training every three
(3) years.
Y
 
CO-Principal Investigator
Name of Co-Principal Investigator
(This could be another faculty or a
Master's or Ph.D. student)
Degree
Title
Kindred, John
Graduate Assistant
Email
Phone
Fax
John.Kindred@colostate.edu
Department Name
Campus Delivery Code
 
1582 Dept Hlth & Exer Sci
 
 Human Subjects Training Completed? Training is required for Co-PI. Training
must be updated every three (3) years.
Y
No training data is available.
 
Additional Co-Principal Investigator
Name of Additional Co-Principal
Investigator
Degree
Title
Ketelhut, Nathan
Graduate Assistant
Email
Phone
Fax
Nathan.Ketelhut@colostate.edu
Department Name
Campus Delivery Code (CSU) or off-
campus mailing address
 
1582 Dept Hlth & Exer Sci
 
 Human Subjects Training Completed? Training is required for Co-PI.
Training must be updated every three (3) years.
Y

Page 4 of 25
 
Name of Additional Co-Principal
Investigator
Degree
Title
Proessl, Felix
Graduate Assistant
Email
Phone
Fax
Felix.Proessl@colostate.edu
Department Name
Campus Delivery Code (CSU) or off-
campus mailing address
 
1582 Dept Hlth & Exer Sci
 
 Human Subjects Training Completed? Training is required for Co-PI.
Training must be updated every three (3) years.
Y
 
Department Head  Mandatory
Name of Department Head
Degree
Title
Braun, Barry
Professor
Email
Phone
Fax
Barry.Braun@colostate.edu
(970) 491-7875
Department Name
Campus Delivery Code
 
1582 Dept Hlth & Exer Sci
 
 Human Subjects Training Completed?? Training is not required for
Department Head. Select "No" if you do not know if your Department Head has
completed training or not.
Y
 
Administrative Contact
Name of Administrative Contact,
Project Director, or Lab Coordinator
Degree:
Title
Biela, Laurie
Email
Phone
Fax
Laurie.Biela@colostate.edu
Department Name
Campus Delivery Code
 
1582 Dept Hlth & Exer Sci
 
 Human Subjects Training Completed? Training is not required for
Administrative Contacts
Y
No training data is available.
 
---------------------------------------------------------------------------------------------
* * * Subject Population * * *
 
 
Subject Population(s) Checklist
        Â Select All That Apply - Note that this is your Targeted Population :
X
 Adult Volunteers
 Decisionally Challenged
Elderly
 Employees
 Fetuses

Page 5 of 25
 
X
 Long-Term Patients
 Mentally Disabled
 Minors (under 18)
 Pregnant Women
 Prisoners
 Soldiers
 Students
 Other (i.e., non-English Speaking or any population that is not specified above)
       
---------------------------------------------------------------------------------------------
* * * Study Location * * *
 
 
Study Location(s) Checklist
         Select All That Apply - NOTE: Check "Other" and input text: 1.) If your study location is not listed, or 2.) If
you would like to list details of your already-checked location (e.g., specific school within a school district)
Aims Community College
Colorado Department of Public Health & Environment
X
Colorado State University
Colorado State University - Pueblo Campus
Denver Public Schools
Greeley/Evans School District
Poudre School District
University of Colorado Health - North (Formerly -Poudre Valley Health System - PVHS)
Rocky Mountain National Park
Thompson School District
University of Colorado - Boulder
University of Colorado - Colorado Springs
University of Colorado - Denver
University of Colorado Health Sciences Center
University of Northern Colorado
Other (In the box below, list your study location if not checked above. You may also list details of your
already-checked location (e.g., specific school within a school district).
       
---------------------------------------------------------------------------------------------
* * * General Checklist * * *
 
General Checklist
         Select All That Apply :
X
Proposed Start Date (cannot be before IRB approval):
Sept. 25, 2016
Sponsored Project (Check if you will be funded OR if you have or plan to submit a grant application in
association with this protocol)
NSF Sponsored (Please upload mandatory Data Management Plan in the Attachment section)
FDA or EPA-regulated research.  Please contact the CSU Quality Assurance Manager, Cat Bens, at 970-
491-5445 to determine if your study is under Good Laboratory, Good Clinical, or Good Manufacturing
Practices (GLP, GCP, GMP).
 Training Grant
Clinical Trial.  To register your trial on Clinicaltrials.gov, please contact Cat Bens, CSU Quality Assurance

Page 6 of 25
 
Manager and Clinical Trails Administrator at:  970-491-5445.
Project is associated with the Colorado School of Public Health - CSPH(faculty and/or student)
Cooperating/Collaborating Institution(s) Institution
where recruitment will occur OR Institution where
Collaborating PI will conduct associated research.
Interview
Questionnaire/Survey
 Subjects will be compensated for participation
Thesis or Dissertation Project
ÃÂ Radioisotopes/radiation-producing machines, even if standard of care.  Please contact Jim Abraham,
Radiation Safety Officer for questions related to use of all radiation-producing machine:  970-491-3736;
james.abraham@colostate.edu.  Upload your radiation-use approval  (if available) or your Radiation Safety
Training certificate in the attachment section.
Human blood, cells, tissues, or body fluids. You will need to obtain IBC approval if you check this box. For
information regarding IBC approval, contact Christine Johnson, IBC Coordinator:
christine.johnson@colostate.edu
 Tissues to be stored for future research projects
 Tissues to be sent out of this institution as part of a research agreement
Human Embryos. You will need to obtain IBC approval if you check this box. For information regarding IBC
approval, contact Christine Johnson, IBC Coordinator:  christine.johnson@colostate.edu
Human Embryonic Cells? Provide NIH Code Number(s)
or state that no federal funding will be used to support
this research. You may need to obtain IBC approval if
you check this box. For information regarding IBC
approval, contact Christine Johnson, IBC Coordinator:
christine.johnson@colostate.edu
 Use of Patient-related equipment? If Yes, specify what equipment is being used.
Medical equipment used for human patients/subjects also used on animals. For questions regarding animal
use approval, contact Elaine Kim, IACUC Senior Coordinator:  491-0236
Protocol involves studying potentially addicting drugs. For questions regarding approval for possession of
controlled substances, contact Chris Giglio, DRC Coordinator:  491-4830; Chris.Giglio@colostate.edu.
Investigational drugs, reagents, or chemicals (IND)
 Commercially available drugs, reagents, or other chemicals administered to subjects (even if they are not
being studied)
X
Investigational Device (IDE)
Cancer Subjects (e.g., clinical trials, behavior/prevention) or Cancer Tissues (e.g., blood, cells, body fluids).
You may need to obtain IBC approval if you check this box. For information regarding IBC approval, contact
Christine Johnson, IBC Coordinator:  christine.johnson@colostate.edu
Other (clarify in text box to the right)
---------------------------------------------------------------------------------------------
* * * Funding * * *
 
Please complete this section if:  1. This protocol will be funded, 2. You have submitted or will submit a grant
application associated with this protocol.  Please be sure to input your PASS/SP1 number to assist Sponsored
Programs in setting up an account for your funds.
If this protocol is funded by the NIH or NSF, or will lead to the regulatory involvement of the FDA or EPA, please
be certain you are cognizant of any specific regulatory requirements for data acquisition, storage, retention and
sharing, as well as research expenditure allowability, with regard to this IRB protocol.
 
Funding Checklist
NONE

Page 7 of 25
 
  
  
NOTE: Applicable Federal Grant Application, including competing renewals, must be attached in the
Attachment Section (#16). Applicable investigator's brochure and sponsor's protocol must also be
attached in section #16 for all industry-sponsored clinical trials.
 
Funding - Grants/Contracts
Funding - Fellowships
Funding - Other
 
Gift Funding
Dept. Funding
Other Funding
Other Fund Name
Rocky Mountain ACSM
Account #, if known
n/a
---------------------------------------------------------------------------------------------
* * * Expedited Paragraphs * * *
 
PLEASE READ:  This online application is for projects that will be reviewed by the IRB via the expedite or full-
board review process.  The criteria for expedited review are listed below. Review and check what expedite
criteria is/are appropriate for your project. NOTE:  If your research involves or may involve greater than minimal
risk, an element of deception, or is FDA-regulated research, do NOT check any of the expedited criteria listed
below.  Your protocol will then be reviewed by the full-board at their next regularly scheduled meeting.  If your
project meets the exempt criteria, please submit your exempt application via email to:
RICRO_IRB@mail.colostate.edu.  Information regarding exempt applications can be found here:
http://ricro.colostate.edu/IRB/ExemptReview.html
 
  Expedite Criteria:
 
1.
Clinical studies of drugs and medical devices only when condition (a) or (b) is met.
 
a) 
Research on drugs for which an investigational new drug application (21 CFR Part 31,32) is
not required. (Note: Research on marketed drugs that significantly increases the risks or
decreases the acceptability of the risks associated with the use of the product is not eligible
for expedited review.)
 
b) 
Research on medical devices for which                                                                                       
                             
 
      i) 
An investigational device exemption application (21 CFR Part 812) is not required; or
      ii) 
The medical device is cleared/approved for marketing and the medical device is being used in
accordance with its cleared/approved labeling.

Page 8 of 25
 
 
2.
Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:
 
a) 
From healthy, nonpregnant adults who weigh at least 110 pounds. For these subjects, the
amounts drawn may not exceed 550 ml in an 8- week period and collection may not occur
more frequently than 2 times per week; or
 
b) 
From other adults and children, considering the age, weight, and health of the subjects, the
collection procedure, the amount of blood to be collected, and the frequency with which it will
be collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3
ml per kg in an 8-week period and collection may not occur more frequently than 2 times per
week.
 
3.
Prospective collection of biological specimens for research purposes by non-invasive means.
 
4.
Collection of data through non-invasive procedures (not involving general anesthesia or sedation)
routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where
medical devices are employed, they must be cleared/approved for marketing. (Studies intended to
evaluate the safety and effectiveness of the medical device are not generally eligible for expedited
review, including studies of cleared medical devices for new indications.)
 
Examples:
a) 
Physical sensors that are applied either to the surface of the body or at a distance and do not
involve input of significant amounts of energy into the subject or an invasion of the subject's
privacy;
b) 
Weighing or testing sensory acuity;                                                                                              
           
c) 
Magnetic resonance imaging;                                                                                                      
     
d) 
Electrocardiography, electroencephalography, thermography, detection of naturally occurring
radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow,
and echocardiography;
e) 
Moderate exercise, muscular strength testing, body composition assessment, and flexibility
testing where appropriate given the age, weight, and health of the individual.
 
5.
Research involving materials (data, documents, records, or specimens) that have been collected, or
will be collected solely for nonresearch purposes (such as medical treatment or diagnosis). (NOTE:
Some research in this paragraph may be exempt from the HHS regulations for the protection of
human subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)
 
6.
Collection of data from voice, video, digital, or image recordings made for research purposes.
 
7.
Research on individual or group characteristics or behavior(including, but not limited to, research on
perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and
social behavior) or research employing survey, interview, oral history, focus group, program
evaluation, human factors evaluation, or quality assurance methodologies. (NOTE: Some research in
this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR
46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.)
 
 
---------------------------------------------------------------------------------------------
* * * Purpose,Study Procedures,Background * * *
 
Original Protocol Number (e.g., 07-226H)
   
Title (Please indicate if the protocol title is different from the proposal title)

Page 9 of 25
 
Can transcranial direct current stimulation improve ambulation and fatigue resistance in people with MS?
 
      Complete Sections 1 - 16. Specify N/A as appropriate. Do not leave any required sections blank.
1. Purpose of the study
a)
Provide a brief lay summary of the project in <200 words.  The lay summary should be readily
understandable to the general public, and is, for example, what would be released to a newspaper if
requested.
In this project we will be using non-invasive brain stimulation on people with multiple sclerosis (PwMS) to
improve leg muscle function. Two groups of participants will be recruited. One group will perform strength
testing with and without the brain stimulation. After completing the strength testing they will walk for six
minutes to see if any increases in strength translate into improve mobility. The second group will perform a
fatigue task, pulling against a wire at a low level of force, with and without the brain stimulation. This type
of brain stimulation has been shown to transiently improve strength and fatigue measures in other
populations, e.g. aged, Parkinson’s, and improve cognitive abilities in people with multiple sclerosis. It is
our hope that the increases in performance seen in other patient groups will also occur in people with
multiple sclerosis. Future investigations will look to apply the non-invasive brain stimulation technique
during physical rehabilitation to improve short and long term outcomes related to physical function.
 
b)
What does the Investigator(s) hope to learn from the study?
We expect to show that transcranial Direct Current Stimulation (tDCS) is an effective method for improving
neuromuscular function in PwMS. With this information we plan to investigate the concurrent use of tDCS
and physical rehabilitation and identify if tDCS can increase the gains seen with traditional PT and if these
improvements last longer compared to when only physical therapy is performed.
 
c)
Proposed Start Date (may not precede IRB approval date):
Oct. 1, 2016
 
2. 
Study Procedures (If this is a student project, the methods section of the thesis or dissertation proposal
must be attached in section #16 - Attachment section.)
 
a)
In lay language, describe all the procedures, from screening through end-of-study, that the human subject
must undergo in the research project, including study visits, drug treatments, randomization and the
procedures that are part of standard of care.  Please note: Do NOT respond "See Attachment Section." If
you would like to add tables, charts, etc., attach those files in the Attachment section (#16).
To investigate the effects of tDCS on strength and fatigue of the leg muscles in patients with multiple
sclerosis (MS) we will employ and randomized blinded cross-over design. Once accepted into the study
participants will be randomized into 1 of 4 groups. Group 1 and 2 will perform leg strength testing followed
by a 6 minute walk test. Groups 3 and 4 will perform a fatigue task. Each group will perform the same
procedures during 2 different visits with 1 visit having a tDCS sham procedure performed and 1 visit
performing the task with tDCS. The order of the sham / treatment will be based on the participant’s group
assignment. Each visit will be separated by at least 7 days. See attachment for proposal timeline.
Participant Recruitment:
Prospective participants will be recruited from the: Integrative Neurophysiology Laboratory’s (INPL)
participant database; the clinical practice of Dr. William Shaffer, Banner Health, Greeley CO; and through
advertisements in the Colorado and Wyoming Chapter of the National MS Society newsletters. All
experimental procedures will be performed in the INPL (Director: Thorsten Rudroff, PhD, FACSM).
Interested individuals will perform an initial screening via an online questionnaire, hosted by Qualtrics,
which has an agreement with the College of Health and Human Sciences. Contact information for the
prospective participants’ information will be accessible only to the research staff according to HIPPA
regulations. After completion of the online screening form, INPL personal will contact 40 eligible
participants, 10 for each group, via phone to confirm their participation and schedule the participant’s first
visit. Once eligibility is confirmed participants will be randomly assigned to 1 of the 4 groups using a
random number generator. If by chance a group fills, 10 participants assigned, before the others that
number will then be removed to ensure each group has a similar size.
Experimental Sessions:

Page 10 of 25
 
The experimental protocol for this study consists of two testing sessions. The following procedures are
common to the Strength Group and the Fatigue Group in session 1. Upon arrival to the INPL the
investigators will explain the protocol and received signed informed consent from the participants.
Participants will also complete the Fatigue Severity Scale (FSS) and the Beck’s Depression Inventory
(BDI) questionnaires. Body composition will be assessed via Dual-Energy X-Ray Absorptiometry (DXA)
utilizing standard guidelines set forth by the Department of Health and Exercise Science. Following
consent, questionnaires, and DXA each participant will being procedures specific to their randomized
group. Group 1 = strength testing, tDCS → Sham; Group 2 = strength testing, Sham → tDCS; Group 3 =
fatigue testing, tDCS → Sham; Group 4 = fatigue testing, Sham → tDCS
Strength Group Session 1
After completion of the questionnaires participants will begin strength testing of the knee extensors/flexors,
planter/dorsi flexor muscle groups. The participants will perform these measurements while seated with the
hip, knee, and ankle at 90 degrees of flexion. All procedures, including those for the fatigue group, will be
performed with the participants in this positon. Between muscle group testing and tDCS application
participants will be allowed to get up and stretch as needed. A strap attached to a linear force transducer
(Noraxon, Scottsdale AZ, USA) will be placed around the participant’s ankle or metatarsals. Once in the
proper position participants will be verbally encouraged to increase to maximal isometric force output over
3 seconds, continue maximal isometric force output for 1-2 more seconds , and then relax. After each
maximal voluntary contraction (MVC) the participants will recover for no less than 60 seconds. Each
muscle group will be tested 3-5 times, or until there is no further increase in force produced or if force
produced is lower than the previous trial. Both the right and left legs will be tested.
After the initial MVCs are performed participants will be asked to self-report their more- and less-affected
legs. Investigators will confirm the self-reported values with the results from the strength testing. Once the
more-affected leg has been determined surface electromyography (sEMG) electrodes will be placed on the
rectus femoris, vastus lateralis, and vastus medialis oblique, -longus. Prior to performing the experimental
paradigm, we will use Transcranial magnetic stimulation (TMS) (Magstim Rapid magnetic stimulator (The
Magstim Company Ltd, Spring Gardens, Whitland, Carmarthenshire, UK)) and a focal figure of eight coil
(diameter of each wing 70 mm) to identify the right hemisphere M1 hotspot for the left leg extensors.  The
coil will be placed tangential to the scalp with the handle pointing 90° away from the midline (Groppa et al.,
2010).  The optimum site in the right M1 (hotspot) for eliciting motor responses in the left leg extensors will
be identified at supra-threshold intensity. Resting motor threshold (RMT) will be determined to the nearest
1% of the maximum stimulator output.  Using standard protocol, the RMT will be defined as the minimum
stimulus intensity that elicited MEPs of 50 mV in at least 5 out of 10 consecutive trials (Triggs et al. 1994).
Once the leg motor cortex of the more-affected side (left or right) has been identified via TMS, a tDCS
device (Neuroelectrics Inc., Simi Valley, CA, USA) will deliver a small direct current through two sponge
surface electrodes (3cm × 3cm, soaked with 15 mM NaCL)(Dundas et al. 2007). The anodal electrode will
be placed over the representation of the motor cortex for the more affected leg, and a second electrode will
be placed on the forehead above the contralateral orbit. The intensity of the tDCS will be 2 mA applied for
10 minutes, starting at 0 and increasing to 2 mA over a 30 second period of time. At the 9:30 time point the
current will gradually be reduced from 2 mA to 0 mA. Anodal tDCS with these parameters has been
reported to change the excitability of the leg motor cortex without inducing side effects (Jeffery et al. 2007).
The used parameters are in accordance with a safety criterion and far below the threshold for tissue
damage (Nitsche et al. 2003). The voltage during tDCS application will be less than 10 V. During the
application of the tDCS current participants will perform strength testing for more-affected side using the
same procedures as the initial MVC acquisition. All MVC will be collected within the 10 min tDCS
stimulation time. Participants receiving a sham condition will only receive the initial 30 seconds of
stimulation, after which the current will be set to 0. These parameters for sham stimulation were chosen
based on previous reports that the perceived sensations on the skin, such as tingling, usually fade out in
the first 30 s of tDCS (Nitsche et al. 2003; Paulus, 2003). The participants and the investigator performing
the MVC testing will be blinded to the tDCS condition. Participants will not be told their strength values until
the end of all testing sessions.
After completion of the tDCS/Sham strength assessment participants will perform a 6 minute walk test. The
test will be performed in a cordoned off hallway with 2 cones placed 30 meters apart. Once the participants
begin walking, a timer will be started and the distance covered every min will be recorded. Participants are
allowed to stop and rest during the test if required. Every minute during the walk test participants will be
asked their rating of perceived exertion (RPE, 0-10 scale) (Dalgas et al. 2014)
Strength Group Session 2
After no less than 7 days, participants will return to the INPL to perform their final session. All procedures
for Session 2 will be the same as in Session 1, except that participants who received tDCS will now
receive sham stimulation and those that received the sham treatment will receive tDCS.
In all sessions both, participants and raters will be blinded to the intervention type. The experimenter who

Page 11 of 25
 
will apply the intervention (real tDCS or Sham) will be different from the experimenter determining the
outcome measures.
Fatigue Group Session 1
Once consent, questionnaires, and DXA have been completed, MVCs of the right and left knee extensors
will be performed using the same methods stated before. After MVC performance participants will be
asked which is their more-affected leg and this answer will be compared to the results of the MVC testing.
Once the more-affected leg is determined the investigators will use the same TMS procedures as above to
identify the more-affected leg’s representation in the motor cortex. The anode tDCS electrode will then be
place in this spot, and stimulation will begin 5 min prior to the start of the fatigue task. After 30 secs the
current will be lowered to 0 for the Sham group. The treatment group will receive stimulation until the end
of the fatigue task or for an additional 15 min, whichever condition occurs first. tDCS blinding and
procedures are the same as they are for the strength group. Both participant and investigator will be
blinded to the treatment.
The fatigue task will consist of the participants performing an isometric contraction of the knee extensors.
Participants will be positioned with the hip, knee, and ankle of the more-affected leg at 90 degrees of
flexion. Just prior to the initiation of the fatigue task the participant will perform 1 MVC, and 30% of this
force output will be the target output of the fatigue task. Visual feedback will be provided on a computer
monitor. Participants will perform the task until they can no longer generate the needed force (within 5% of
the target value for 5 seconds), or they say they want to stop. At every 1 minute interval the participant will
be asked to provide their rating of perceived exertion (RPE) based on the modified Borg 10 point scale.
The required leg position will be monitored by visual inspection, and feedback will be given to the subject
by the same investigators for all experiments. Immediately after task failure another MVC with the knee
extensors will be performed to quantify the decline in strength.
Fatigue Group Session 2
After no less than 7 days, participants will return to the INPL to perform their final session. All procedures
for Session 2 will be the same as in Session 1, except that participants who received tDCS will now
receive sham stimulation and those that received the sham treatment will receive tDCS.
In all sessions both, participants and raters will be blinded to the intervention type. The experimenter who
will apply the intervention (real tDCS or Sham) will be different from the experimenter determining the
outcome measures.
Electromyography (EMG)
During all strength and fatigue testing EMG signals will be recorded with bipolar surface electrodes that will
be placed over the vastus medialis oblique, vastus medialis longus, rectus femoris, vastus lateralis, and
biceps femoris. The electrodes will be attached according to landmarks between the innervation zone and
the end of the tendon (Rainoldi et al. 2004, 2007). The EMG signals will be amplified (x 2,000), band-pass
filtered (13–1,000 Hz; Noraxon) and recorded on a computer.
 
b)
Explain why human subjects must be used for this project.
The goal of this project is to determine if tDCS can increase leg muscle strength and fatigue resistance in
people with MS. Therefore all clinical testing needs to be performed in the patient population that is being
studied.
 
c)
Alternative Procedures. If the proposed study is a clinical trial of a drug, vaccine, device or treatment,
describe alternative procedures, if any, that might be advantageous to the subject. Describe the important
potential risks and benefits associated with the alternative procedure(s) or course(s) of treatment. Any
standard treatment that is being withheld must be disclosed. This information must be included in the
consent form.
N/A
 
d)
If the proposed study is a clinical trial of a drug, vaccine, device or treatment, will it be possible to continue
the more (most) appropriate therapy for the subject(s) after the conclusion of the study?
N/A
 
e)
Study Endpoint. If the proposed study is a clinical trial of a drug, vaccine, device or treatment, what are the
guidelines or end points by which you can evaluate the alternative treatments during the study? If one
treatment proves to be clearly more effective than another (or others) will the study be terminated before

Page 12 of 25
 
treatment proves to be clearly more effective than another (or others) will the study be terminated before
the projected total subject population has been enrolled? When will the study end if no important
differences are detected?
N/A
 
f)
State if deception will be used. If so, provide a rationale and describe debriefing procedures. Submit a
debriefing script in the Attachment Section (#16).
N/A
 
3. Background
a)
Describe past experimental and/or clinical findings leading to the formulation of the study, if applicable.
Our previous studies showed asymmetries in muscle activities during walking in PwMS (Rudroff et al.2015,
Ketelhut et al. 2015). The next step is now to investigate the underlying mechanisms and possible
rehabilitation treatments.
 
b)
Describe any animal experimentation and findings leading to the formulation of the study, if applicable.
N/A
---------------------------------------------------------------------------------------------
* * * Radioisotopes or Radiation Machines * * *
 
 
You selected NO for Radioisotopes in the General Checklist. If you would like to add Radioisotopes, change the
selection to YES in general Checklist.
 
4. 
Radioisotopes or Radiation Machines Please note: For projects requiring radiation procedures, please
contact the CSU Radiation Control Office (RCO). For more information see:
http://www.ehs.colostate.edu/WRad/Home.aspx :
 
 
a) 
If applicable, summarize in lay language the radiographic diagnostic and therapeutic procedures
associated with this protocol.
The DEXA scan that will be performed during this study uses radiation to assess bone mineral
density and body composition at pre treatment.
  b) 
Are the radiation procedures being performed a normal part of the clinical management for the medical
condition that is under study (Standard of Care) or are the procedures being performed because the
research subject is participating in this project (extra CT scans, more fluoroscopy time, additional Nuclear
Medicine Studies, etc.,) (Not Standard of Care)? If some procedures are Standard of Care and some are
Not Standard of Care, check both boxes.
 
  
NOT STANDARD OF CARE
STANDARD OF CARE
  
If it is not standard of care, complete the rest of
this section. Provide the CSU RCO approval
information
If it is only standard of care, skip the rest of this
section.
 
 
CSU Radiation Control Office approved protocol number:
 
 
CSU Radiation Control Office protocol approval date:
 

Page 13 of 25
 
For more information, see the RCO website at:http://www.ehs.colostate.edu/Wrad/home.aspx or Contact:
James Abraham, Radiation Safety Officer, at 970-491-3736.
---------------------------------------------------------------------------------------------
* * * Medical Equipment for Human Subjects and Laboratory Animals; Investigatiional Devices * * *
 
 
5. Medical Equipment for Human Subjects
 
  
If medical equipment is being used for human subjects/patients, describe this equipment and indicate if the
use is normal practice for the population under study. You may have already described this equipment in
the Study Procedures section. If you have already listed this information in the Study Procedures Section,
please do not duplicate this information here. In the space below, input N/A if not applicable, indicate if this
is already listed in the Study Procedures Section, or describe the equipment.
N/A
 
 
6. Investigational Devices
         Please list in the space below all Investigational Devices to be used on Subjects.
Investigational Devices
Investigational Devices
Describe the device(s) to be used
ActivaDose II Iontophoresis Delivery Unity
Device Name
ActivaDose II Iontophoresis Delivery Unity
Manufacturer
ActivaTek, Inc.
Significant risk
Y
Non-Significant risk
IDE #
Rationale for Non-Significant Risk Device
Class 2 device.
If a non-significant risk device study is indicated, provide rationale for the device being non-significant risk.
Please state if you need IRB guidance on whether this is a significant or non-significant risk device.
---------------------------------------------------------------------------------------------
* * * Drugs, Reagents, or Chemicals * * *
 
 
7. Drugs, Reagents, or Chemicals
 a)
Please list in the space below all investigational drugs, reagents or chemicals to be administered to
subjects during this study.
 
 b)
Please list in the space below all commercial drugs, reagents or chemicals to be administered to subjects
during this study.
 
 
Please read the IND Statements
---------------------------------------------------------------------------------------------
* * * Subject Population (a-g) * * *

Page 14 of 25
 
 
 
8.  
Subject Population - In the space below, please detail the participants that you are requesting to recruit
(include requested participant number and description of each group requested).  (Input N/A if not
applicable)
a)
Requested Participant Description (Include number of participants that you plan to study and description of
each group requested, if applicable).
N/A
 
b)
What is the rationale for studying the requested group(s) of participants?
To investigate the effects of tDCS on leg muscle strength and fatigue.  The research team has experience
with all the methods involved.
 
c)
If applicable, state the rationale for involvement of potentially vulnerable subjects to be entered into the
study, including minors, pregnant women, economically and educationally disadvantaged, or decisionally
impaired subjects. Specify the measures being taken to minimize the risks and the chance of harm to the
potentially vulnerable subjects.
N/A
 
d)
If women, minorities, or minors are not included, a clear compelling rationale must be provided. Examples
for not including minors: disease does not occur in children; drug or device would interfere with normal
growth and development; etc.
N/A
 
e)
State if any of the subjects are students, employees, or laboratory personnel. They should be presented
with the same written informed consent. If compensation is allowed, they should also receive it.
N/A
 
f) 
Describe how potential subjects will be identified for recruitment (e.g., chart review, referral from individual's
treating physician, those individuals answering an ad). How will potential participants learn about the
research and how will they be recruited (e.g., flyer, email, web posting, telephone, etc.)? Attach recruitment
materials in the Attachment Section (#16). Important to remember: potential subjects may not be contacted
before IRB approval.
Prospective participants will be recruited from the Integrative Neurophysiology Laboratory’s (INPL)
participant database, the clinical practice of Dr. William Shaffer, Banner Health, Greeley CO, and through
advertisements in the Colorado and Wyoming Chapter of the National MS Society newsletters. All
experimental procedures will be performed in the INPL (Director: Thorsten Rudroff, PhD, FACSM).
Interested individuals will perform an initial screening via an online questionnaire, hosted by Qualtrics,
which has a contract with the College of Health and Human Sciences. Contact information for the
prospective participants’ information will be accessible only to the research staff according to HIPPA
regulations. After completion of the online screening form, INPL personal will contact eligible participants
via phone. INPL staff will schedule the participants’ first visit (30 total).
 
g) 
If applicable, provide rationale for the inclusion of healthy volunteers in this study. Specify any risks to
which these healthy volunteers may possibly be exposed. Specify the measures being taken to minimize
the risks and the chance of harm to these volunteers.
N/A
---------------------------------------------------------------------------------------------
* * * Subject Population (h-m) * * *
 
 

Page 15 of 25
 
8. Subject Population (Input N/A if not applicable)
h)
Inclusion and Exclusion Criteria (e.g., Participants must have 20/20 vision, Participants must be 30-45
years of age, etc.)
 
 
  
   
Identify inclusion criteria.
Medically diagnosed with MS, 30-60 years of age, Moderate disability (Patient Determined
Disease Steps score 2-6), self-reported differences in function between the legs (2-5 on a 1-5
scale).
 
 
  
   
Identify exclusion criteria.
•A relapse of disease symptoms in the last 60 days
•A condition unrelated to MS that would exacerbate fatigue, such as anemia, hypothyroidism,
shiftwork-related fatigue, B12 deficiency, major sleep disorder, or major depressive disorder
•Medical diagnosis or condition that  makes participating in exercise training dangerous, such
as major renal, pulmonary, hepatic, cardiac, gastrointestinal, HIV, cancer (other than treated
basal cell cancer), other neurological disorders, or pregnancy
•History of heart attack or current diagnosis of cardiovascular disease
•History of seizure disorders (or on medications known to lower seizure threshold),
•       Hydrocephalus (i.e. buildup of fluid in the brain)
•Alcohol dependence or abuse (>2 drinks/day), or present history (last six months) of drug
abuse
•History of significant traumatic brain injury
•Pregnancy
•Recent hospitalization (within the last 3 months) or enforced bed rest/sedentary state.
•Presence of metal is present or implanted device or metal object that is not safe for TMS.
•Presence of holes or fissures of the cranial bones
 
i)
Describe your screening procedures. Attach your screening document(s) (e.g., health history
questionnaire) in the Attachment Section (#16).
Prospective participants will be screened via an online questionnaire. This questionnaire will gather contact
information, date of birth, height, weight, self-reported disability status, and cardiovascular risk factors.
 
j)
Describe how you will be cognizant of other protocols in which subjects might be participating. Please
explain if subjects will be participating in more than one study.
This will be the only study participants will be in.
 
k)
Compensation. Explain the amount and schedule of compensation, if any, that will be paid for participation
in the study. Compensation includes food, gift cards, money, tokens, etc. Include provisions for prorating
payment, if applicable.  Compensation should be prorated if several activities are involved for different time
periods (e.g., $10 for session #1, and $10 for session #2).
Subjects in the fatigue group will be compensated $20 upon completion of the study.
 
l)
Costs. Please explain any costs that will be charged to the subject.
None, participants are only responsible for their transportation to/from campus.
 
m)
Estimate the probable duration of the entire study. This estimate should include the total time each subject
is to be involved and the duration the data about the subject is to be collected (e.g., This is a 2-year study.
Participants will be interviewed 3 times per year; each interview will last approximately 2 hours.  Total
approximate time commitment for participants is 12 hours).  These times should be consistent with the time
commitment listed on the consent document.
Participants will be expected to spend approximately 2.5-3 hours split over 2 session. We expect data
collection to last 6 months.
---------------------------------------------------------------------------------------------

Page 16 of 25
 
* * * Risks * * *
 
 
9. Risks (Input N/A if not applicable)
     
US Department of Health & Human Services (HHS) Regulations define a subject at risk as follows: "...any
individual who may be exposed to the possibility of injury, including physical, psychological, or social injury,
as a consequence of participation as a subject in any research, development, or related activity which
departs from the application of those accepted methods necessary to meet his needs, or which increases
the ordinary risks of daily life, including the recognized risks inherent in a chosen occupation or field of
service."
 
 a) 
PI's evaluation of the overall level of Risk. (Please check one: minimal or > minimal.)
Y
Minimal (everyday living)
> Minimal (greater than everyday living)
 
 b)   
For the following categories include a scientific estimate of the frequency, severity, and reversibility of
potential risks. Wherever possible, include statistical incidence of complications and the mortality rate of
proposed procedures. Where there has been insufficient time to accumulate significant data ON risk, a
statement to this effect should be included. (In describing these risks in the consent form to the subject, it is
helpful to use comparisons which are meaningful to persons unfamiliar with medical terminology.) Address
any risks related to:
 
 
   
   
1.   
Use of investigational devices. Please include the clinical adverse events (AEs) associated with
each of the devices with an indication of frequency, severity and reversibility. This information
can often be found in the Investigator(s) brochure.
N/A
 
 
   
   
2   
Use of investigational drugs. Please include the clinical AEs associated with each of the drugs
with an indication of frequency, severity and reversibility. This information can often be found in
the Investigator(s) brochure.
N/A
 
 
   
   
3   
Use of commercially available drugs, reagents or chemicals. Please include the clinical AEs
associated with each of the drugs with an indication of frequency, severity and reversibility. This
information can often be found in the package insert provided by the manufacturer.
N/A
 
 
   
   
4   
When performing procedures, please include all investigational, non-investigational and non-
invasive procedures (e.g., surgery, blood draws, treadmill tests).
Participants will perform maximal voluntary strength tests with the leg extensors, -flexors, and
dorsiflexors and a 6 min walk test to determine how far they can walk in 6 min. They will also
perform a fatigue task (isometric contraction) with the more affected leg.
There is a risk of muscle/tendon strain with the exercises.
 
 
   
   
5  
Radioisotopes/radiation-producing machines(e.g., X-rays, CT scans, fluoroscopy).

Page 17 of 25
 
N/A
 
 
c)      
For the following categories, include an estimate of the potential risk, if applicable.
 
 
   
   
1.   
Physical well-being.
Potential risks include: skin irritation to surface electromyography electrodes, muscle
cramps/spasms during strength testing.
tDCS safety
tDCS is a non-invasive brain stimulation technique in which a very weak electrical current is
applied to the scalp. tDCS has been conducted on humans and animals for many years and no
evidence has emerged to suggest that it is harmful or has ever induced a serious side effect.
However, the safety of tDCS is dependent on current strength, electrode size, and stimulation
duration. Accordingly, these parameters have been investigated to establish safe and effective
stimulation parameters for tDCS applications in research involving human subjects. The only
side effects that have been reported when proper guidelines are followed are temporary
tingling, itching, headache, or skin redness under the electrodes in some subjects. For
example, a 2008 review of the approximately 100 human tDCS studies up until that time on
healthy adults and patients found that 64 of these studies reported no side effects, 24 studies
reported a temporary itching or tingling under the electrodes in some subjects, and one study
reported skin redness. Furthermore, these slight side effects were of equal occurrence in
subjects that received placebo stimulation in 7 studies. In addition, only two subjects in these
100 studies reported a mild headache. Similar findings have recently been reported in research
and review articles (Nitsche et al. 2008; Hummel et al. 2008).
Physiological studies have also assessed the safety of tDCS when applied within the
aforementioned stimulation guidelines. For example, there was no neuronal damage as
measured by serum neuron-specific enolase (Stagg & Nitsche, 2011 ) or MRI measures of
edema using contrast enhanced and diffusion-weighted MRI measures following administration
of tDCS (Nitsche et al. 2004). Furthermore, tDCS did not negatively alter measures of
neuropsychological function and EEG activity (Iver et al. 2005). Accordingly, rat studies using
tDCS models emulating tDCS applied to humans (Liebetanz et al. 2009 ) showed that the
current density needed to induce tissue damage or lesions was about 1429 mA/cm2, whereas
the current densities used in human studies are between 0.04 and 0.08 mA/cm2 and in this
proposal are 0.029 mA/cm2. In conclusion, the tDCS stimulation parameters in this study are
identical to the most common in the literature and have been proven to be exceptionally safe
and well-tolerated.
The probablilty is very unlikely that harm may occur (see above). Based on the availiable
literature a slight headache should be the worst possible negative effect and should be very
rare. In this case, non-prescription medication should relieve the headache within 1-2 hours.
Risks will be  minimized by using safe, well-established procedures and strict monitoring of
each experimental session. Risks are minimized by using stimulation parameters that are well-
described, within international guidelines, and within the range of those used in hundreds if not
thousands of studies (see above).
TMS safety
TMS is a non-invasive brain stimulation technique that can be used for both diagnostic and
therapeutic procedures. The single and paired-pulse TMS techniques performed in this study
have been used extensively in thousands of research studies and on tens of thousands of
subjects in the United States and around the world. Single and paired pulse TMS techniques
are considered very safe (Hallet, 2000, 2007) when accepted guidelines are followed
(Wassermann et al. 1998). Finally, no long-term risks have been reported in the
aforementioned review articles involving the use of TMS.  In general, the risks associated with
TMS are very minimal (Anand et al. 2002; Anderson et al. 2006; Loo et al. 2008).  There is a
very small risk of seizures if rTMS is done with very intense, high frequency stimulation or with
trains of stimulation separated by a second or less (Anand et al. 2002; Anderson et al. 2006;
Loo et al. 2008).  Such intensity, frequency and repetition rate will not be used in this study as
the study does NOT include rTMS and only single and paired pulse TMS methods will be
employed. For most people, the single and paired pulse stimulation is not painful, but

Page 18 of 25
 
occasionally slight discomfort or headache can occur. The headaches go away quickly with
nonprescription medication. The noise caused by TMS pulses may affect hearing; therefore,
subjects will be fitted with earplugs during TMS testing. Finally, there is no medical risk
associated with the surface EMG recordings of the muscle responses to TMS.
 
 
   
   
2.   
Psychological well-being.
None
 
 
   
   
3.   
Economic well-being.
None
 
 
   
   
4.   
Social well-being.
None
 
 d) 
In case of overseas research, or working with a specific race/ethnicity in the United States, provide
background on what experience the Investigator(s) have with the proposed population. Describe
qualifications/preparations that enable the Investigator(s) to evaluate cultural appropriateness and
estimate/minimize risks to subjects.
N/A
 
 e) 
Special Precautions. Describe the planned procedures for protecting against or minimizing potential risks. If
appropriate, include the standards for termination of the participation of the individual subject. Discuss
plans for ensuring necessary medical or professional intervention in the event of adverse effects to the
subjects.
All research staff are certified in CPR, AED, and First Aid by the American Red Cross. Participants are
freely available to stop any procedure at any time.
 
 f) 
Data Safety Monitoring                                                                                          
    
N
Is there a Data Safety Monitoring Board (DSMB)?
 
 
   
   
   
If yes, describe its role and indicate who set up the Data Safety Monitoring Board (e.g., sponsor
or Protocol Director).
 
 
   
   
   
Describe the data and safety monitoring plan developed to ensure the safety of participants and
the validity and integrity of research data. Monitoring should be commensurate with risks and
with the size and complexity of the trials.
---------------------------------------------------------------------------------------------
* * * Benefits, Procedures to Maintain Confidentiality * * *
 
 
10. Benefits (Input N/A if not applicable)
a)
Describe the potential benefit(s) to be gained by the subjects. If there is no direct benefit to the subjects
describe how the results of the study may benefit society or a particular group.

Page 19 of 25
 
There is no personal benefit associated with this protocol, although the outcomes may help improve
rehabilitative procedures for people with MS who have fatigue and leg strength asymmetries.
 
11. Procedures to Maintain Confidentiality
a)
Describe the procedures that protect the privacy of the subjects and maintain the confidentiality of the data.
If a linked list is used, explain when the linked list will be destroyed.  Provide a sample of the code that will
be used, if applicable.
All data collected, including personal identifiable information will be stored either electronically on Colorado
State University secured networks with access restricted to the current investigators. Hard copy data will
be stored in a locked file cabinet that only research personnel have access too. At night second story of
the Health and Exercise Science Department is restricted to authorized key holders, and the room in which
the file cabinet is located is restricted to only current laboratory staff.
 
b)
If information derived from the study will be provided to the subject's personal physician, a government
agency, or any other person or group (other than the research team), describe to whom the information will
be given and the nature of the information, if applicable.
N/A
 
c)
Specify where and under what conditions study data will be kept, how samples will be labeled, who has
access to the data, and what will be available and to whom.  Federal regulations require that study data
and consent documents be kept for a minimum of three (3) years after the completion of the study by the
PI.  For longitudinal projects and federally regulated studies, the PI may be required to keep the data and
documents for a longer time period.
All data collected, including personal identifiable information will be stored either electronically on Colorado
State University secured networks with access restricted to the current investigators. Hard copy data will
be stored in a locked file cabinet that only research personnel have access too. At night second story of
the Health and Exercise Science Department is restricted to authorized key holders, and the room in which
the file cabinet is located is restricted to only current laboratory staff
---------------------------------------------------------------------------------------------
* * * Potential Conflict of Interest * * *
 
 
12. Potential Conflict of Interest
Although you have already submitted CSU's official Conflict of Interest form (FCOI/COI/COC) to the
University, it is the IRB's responsibility to ensure that conflicting interests related to submitted protocols do
not adversely affect the protection of participants or the credibility of the human research protection program
at CSU. Please answer questions a-d below.  Please note that if you indicate that you have a potential
financial or professional conflict of interest in relation to this protocol, your CSU FCOI/COI/COC Reporting
Form must reflect this potential conflict.  Link to CSU's Conflict of Interest policy:
:http://www.facultycouncil.colostate.edu/files/manual/sectiond.htm#D.7.7
a)
N
In connection with this protocol, do you or any of the protocol investigators or their
immediate family members (i.e., spouse and legal dependents, as determined by the IRS)
have a potential financial or professional conflict of interest?
b)
N/A
If you do have a potential conflict of interest, is this reported in your current
FCOI/COI/COC?
c)
N/A
If you do have a potential conflict of interest, is there a management plan in place to
manage this potential conflict?
d)
N/A
If you do have a potential conflict of interest, is this potential conflict of interest included in
your consent document (as required in the Management Plan)?
 
If you have reported a possible conflict of interest, the IRB will forward the title of this protocol to your Research
Associate Dean to complete your COI file. 
 

Page 20 of 25
 
For more information on CSU's policy on Conflict of Interest, please see the Colorado State University
Academic Faculty and Administrative Professional Manual Sections D.7.6 & D.7.7.
:http://www.facultycouncil.colostate.edu/files/manual/sectiond.htm#D.7.7
 
Link to CSU's Conflict of Interest Policy: http://www.provost.colostate.edu/index.asp?url=faculty_affairs.
---------------------------------------------------------------------------------------------
* * * Informed Consent * * *
 
 
13. Informed Consent
NOTE: In order to complete this protocol, you must upload either a Consent Form or an Alteration of
Consent Form (i.e., Cover Letter or Verbal Script) OR (if neither of those apply to your project) you must
complete the Waiver of Consent information.
In the space below, please provide consent process background information for each Consent Form(s),
Alteration of Consent Form(s), or Waiver(s).
Informed Consent
  Title
Fatigue Consent 24July2017
  Consent Information Type
Consent
  Sponsor's Consent Version Number: (if any)
Consent Form Template
X Attachment
 
Amendment_Consent_tDCS_Fati
gue_24July2017 (1) (1)
<a href='http://ricro.colostate.edu/IRB/ConsentAssentTemplates.html' target=_blank Consent Form
Samples
Who is obtaining consent? The person obtaining consent must be knowledgeable about the study and
authorized by the PI to consent human subjects.
How is consent being obtained?
What steps are you taking to determine that potential subjects are competent to participate in the decision-
making process?
  Title
Strength Consent 06JUNE2017
  Consent Information Type
Consent
  Sponsor's Consent Version Number: (if any)
Consent Form Template
X Attachment
 
Consent_tDCS_Strength_201706
06 (4)
<a href='http://ricro.colostate.edu/IRB/ConsentAssentTemplates.html' target=_blank Consent Form
Samples
Who is obtaining consent? The person obtaining consent must be knowledgeable about the study and
authorized by the PI to consent human subjects.
How is consent being obtained?
What steps are you taking to determine that potential subjects are competent to participate in the decision-
making process?
---------------------------------------------------------------------------------------------

Page 21 of 25
 
* * * Assent Background * * *
 
 
14. Assent Background  (Complete if applicable)
All minors must provide an affirmative consent to participate by signing a simplified assent form, unless the
Investigator(s) provides evidence to the IRB that the minor subjects are not capable of assenting because of
age, maturity, psychological state, or other factors.
See sample consent/assent forms at  http://ricro.colostate.edu/IRB/ConsentAssentTemplates.html
Provide assent process background information, in the space below, for each Assent Form, Alteration Form
(i.e., Cover Letter or Verbal Script), and Waiver.
Assent  Background
---------------------------------------------------------------------------------------------

Page 22 of 25
 
* * * HIPAA * * *
 
 
15. HIPAA
Are you using PHI*? (See definition below)
Y
Colorado State University is a hybrid entity and does not have a research-related HIPAA policy. If you will be
working with a HIPAA covered entity (e.g., Poudre Valley Health System), you will need to follow their HIPAA
guidelines. If your project will involve a HIPAA-regulated entity, in the Attachment section (#16) please attach that
entity's required HIPAA consent and/or each waiver of authorization or alteration of authorization requested (e.g.,
waiver of authorization for access to medical records). Include HIPAA authorization language in the consent
document(s) as appropriate (e.g., when enrolling subjects).  
*Protected Health Information (PHI) is health information with one or more of the following identifiers. For
more information see: http://www.hhs.gov/ocr/hipaa/
  1.
Names
  2.
Social Security numbers
  3.
Telephone numbers
  4.
All geographic subdivisions smaller than a State, including street address, city, county, precinct,
zip code, and their equivalent geocodes, except for the initial three digits of a zip code, if,
according to the current publicly available data from the Bureau of the Census: (1) The
geographic unit formed by combining all zip codes with the same three initial digits contains
more than 20,000 people; and (2) The initial three digits of a zip code for all such geographic
units containing 20,000 or fewer people is changed to 000
  5.
All elements of dates (except year) for dates directly related to an individual, including birth date,
admission date, discharge date, date of death; and all ages over 89 and all elements of dates
(including year) indicative of such age, except that such ages and elements may be aggregated
into a single category of age 90 or older
  6.
Fax numbers
  7.
Electronic mail addresses
  8.
Medical record numbers
  9.
Health plan beneficiary numbers
10.
Account numbers
11.
Certificate/license numbers
12.
Vehicle identifiers and serial numbers, including license plate numbers
13.
Device identifiers and serial numbers
14.
Web Universal Resource Locations (URLs)
15.
Internet Protocol (IP) address numbers
16.
Biometric identifiers, including finger and voice prints
17.
Full face photographic images and any comparable images; and
18.
Any other unique identifying number, character, or code (note this does not mean the unique
code assigned by the Investigator(s) to code the research data)
---------------------------------------------------------------------------------------------
* * * Attachments * * *
 
16. Attachments
Attach relevant documents here. These could include: Collaborating Investigator's IRB approval and
approved documents; Conflict of Interest information; Debriefing Script; Grant/Sub-contract; HIPAA
Authorization Form from HIPAA-covered entity; Interview/Focus Group Questions; Investigator's Brochure;
Letters of Agreement/Cooperation from organizations who will help with recruitment; Methodology section of
associated Thesis or Dissertation project; Questionnaires; Radiation Control Office approval material;
Recruitment Material (e.g., flyers, email text, verbal scripts); Sponsor's Protocol; Surveys; Other files
associated with the protocol (you can upload most standard file formats: xls, pdf, jpg, tif, etc.)  Please be
sure to attach all documents associated with your protocol. Failure to attach the files associated with the

Page 23 of 25
 
protocol may result in this protocol being returned to you for completion prior to being reviewed. Students:
Be sure to attach the Methods section of your thesis or dissertation proposal. If this protocol is associated
with a grant proposal, please remember to attach your grant.
To update or revise any attachments, please delete the existing attachment and upload the revised document to
replace it. 
Document Type
Questionnaire/Survey
Attachment
Beck_Depression_Inventory
Document Name
Beck_Depression_Inventory
Document Type
Questionnaire/Survey
Attachment
FSS
Document Name
FSS
Document Type
Other Protocol Material
Attachment
Timeline_tDCS
Document Name
Timeline_tDCS
Document Type
Other Protocol Material
Attachment
References
Document Name
References
Document Type
Other Protocol Material
Attachment
Device Accountability Log
Document Name
Device Accountability Log
Document Type
SOP
Attachment
RestingMotorThreshold_Hotspot_SOP
Document Name
RestingMotorThreshold_Hotspot_SOP
Document Type
Other Protocol Material
Attachment
Rossi2009_TMS_Safety
Document Name
Rossi2009_TMS_Safety
Document Type
Other Protocol Material
Attachment
HIPAA Release generic
Document Name
HIPAA Release generic
Document Type
Letters of Agreement.Cooperation
Attachment
Shaffer Letter _tDCS
Document Name
Shaffer Letter _tDCS
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)

Page 24 of 25
 
Attachment
Recruitment_Flyer_tDCS
Document Name
Recruitment_Flyer_tDCS
Document Type
Questionnaire/Survey
Attachment
MS_tDCS_pilot_screening_20170606
Document Name
MS_tDCS_pilot_screening_20170606
Document Type
SOP
Attachment
ActivaDoseII_manual
Document Name
ActivaDoseII_manual
---------------------------------------------------------------------------------------------
* * * Obligations * * *
 
 
Obligations (Researcher's Responsibilities)
 
The Principal Investigator is ultimately responsible for the conduct of the project. Obligations of the Principal
Investigator are:
 
Conduct the research involving human subjects as presented in the protocol, including modifications, as
approved by the Department and Institutional Review Board. Changes in any aspect of the study (for example
project design, procedures, consent forms, advertising materials, additional key personnel or subject populations)
will be submitted to the IRB for approval before instituting the changes (PI will submit the "Amendment/Revision"
form);
 
Provide all subjects a copy of the signed consent form, if applicable. Investigators will be required to retain signed
consent documents for three (3) years after close of the study;
 
Maintain an approved status for Human Subjects Protection training. Training must be updated every three (3)
years (Contact RICRO to check your current approval/renewal dates). For more information:  Human Subjects
Training Completed?
 
Submit either the "Protocol Deviation Form" or the "Report Form" to report protocol Deviations/Violations,
Unanticipated Problems (UPs) and/or Adverse Events (AEs) that occur in the course of the protocol. Any of these
events must be reported to the IRB as soon as possible, but not later than five (5) working days.  Note that if an
event resulted in life threatening injury or death OR an event resulted in substantive harm to the safety, rights or
welfare to human subjects, this must be reported to the IRB within 24 hours;
 
Submit the "Continuing Review" Form in order to maintain active status of the approved protocol. This form must
be submitted annually at least four (4) weeks prior to expiration, five (5) weeks for protocols that require full
review. If the protocol is not renewed before expiration, all activities must cease until the protocol has been re-
reviewed;
 
Notify the IRB that the study is complete by submitting the "Final Report" form.
 
  
  

Page 25 of 25
 
X
The Principal Investigator has read and agrees to abide by the above obligations.
---------------------------------------------------------------------------------------------
* * * Event History * * *
Event History
Date
Status
View Attachments
Letters
08/22/2016
NEW FORM CREATED
09/01/2016
NEW FORM SUBMITTED
Y
09/06/2016
NEW FORM PANEL
ASSIGNED
09/09/2016
NEW FORM REVIEWER(S)
ASSIGNED
09/12/2016
NEW FORM REVIEWER(S)
ASSIGNED
10/03/2016
NEW FORM REVIEWER(S)
ASSIGNED
10/25/2016
NEW FORM MOVED
10/25/2016
NEW FORM APPROVED
Y
Y
11/09/2016
AMENDMENT 1 FORM
CREATED
11/09/2016
AMENDMENT 1 FORM
SUBMITTED
Y
11/11/2016
AMENDMENT 1 FORM
APPROVED
Y
Y
06/06/2017
AMENDMENT 2 FORM
CREATED
06/06/2017
AMENDMENT 2 FORM
SUBMITTED
Y
06/07/2017
AMENDMENT 2 FORM
REVIEWER(S) ASSIGNED
07/05/2017
AMENDMENT 2 FORM
MOVED
07/05/2017
AMENDMENT 2 FORM
APPROVED
Y
Y
07/26/2017
AMENDMENT 3 FORM
CREATED
07/26/2017
AMENDMENT 3 FORM
SUBMITTED
Y
07/27/2017
AMENDMENT 3 FORM
APPROVED
Y
Y
08/02/2017
CONTINUING REVIEW 1
FORM CREATED
08/24/2017
CONTINUING REVIEW 1
FORM SUBMITTED
Y
09/08/2017
CONTINUING REVIEW 1
FORM REVIEWER(S)
ASSIGNED
09/20/2017
CONTINUING REVIEW 1
FORM APPROVED
Y
Y
07/12/2018
FINAL FORM CREATED
07/12/2018
FINAL FORM SUBMITTED
Y

Consent for Fatigue Group 
 
 
 
 
Page 1 of 8 Participant’s initials _______ Date _______  
Version 24July2017 
 
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 EXPIRES: 9/14/2018 
Consent to Participate in a Research Study 
Colorado State University 
 
TITLE OF STUDY: Can transcranial direct current stimulation (tDCS) improve 
ambulation and fatigue resistance in people with MS? 
 
PRINCIPAL INVESTIGATORS:   
The principal investigator is a researcher in the Department of Health and Exercise 
Science at Colorado State University: 
 
Thorsten Rudroff, Ph.D., FACSM  
 
 
 
 
HES-INPL@mail.ColoState.edu  
970-491-8655 
 
 
 
 
 
 
 
 
 
WHY AM I BEING INVITED TO TAKE PART IN THIS RESEARCH?  
You are an adult aged between 30 and 60 years of age, and you were diagnosed with 
Multiple Sclerosis. 
 
WHO IS DOING THE STUDY?  
Dr. Rudroff and his graduate students John Kindred, Nathan Ketelhut, and Felix Proessl 
are performing the study in the Integrative Neurophysiology Laboratory. 
 
WHAT IS THE PURPOSE OF THIS STUDY? 
The purpose of this study is to determine if a single session of tDCS can increase 
fatigue resistance of the more affected leg in people with MS. 
 
WHERE IS THE STUDY GOING TO TAKE PLACE AND HOW LONG WILL IT LAST?  
The study will take place in the Integrative Neurophysiology Laboratory in the 
Department of Health and Exercise Science, on the Colorado State University campus. 
The study will run for approximately 12 months. You will take part in the study for 
approximately a total of 3 hours over the space of two weeks. 
 
WHAT WILL I BE ASKED TO DO?  
You will be asked to participate in two sessions on two different days separated by no 
less than 7 days.  Each visit will last approximately 90min. 
 
If you participate in this study you will perform strength tests of your leg muscles in 
association with 1 of 2 intervention protocols involving tDCS application (BEFORE and 
SHAM) with each intervention protocol being performed in a separate session on a 
different day.  Thus, in one session you will receive tDCS before the strength test, 
whereas in another session you will receive sham tDCS before the strength test. 
 
Upon arrival to the INPL the investigators will explain the protocol procedures and 
receive signed informed consent from you.  
 

Consent for Fatigue Group 
 
 
 
 
Page 2 of 8 Participant’s initials _______ Date _______  
Version 24July2017 
 
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 EXPIRES: 9/14/2018 
- 
Questionnaires: You will fill out to questionnaires relating to fatigue and 
depression. 
- 
Body Compostion: We will perform a Dual-Energy X-Ray Absorptiometry (DXA) 
scan on you. A very small amount of X-Rays will pass through your body and 
allow us to measure the amount of muscle, fat, and bone you have. 
- 
Leg Strength: The maximal strength of each leg will be measured by having you 
perform a series of maximal effort knee extension trials.  This will be performed 
one leg at a time up to five times. The activity of your muscles will be measured 
during this task by placing a series of electrodes on the skin of your legs. 
- 
Fatigue Task: The fatigue task will consist of an isometric, no movement of the 
legs, contraction of the knee extensors. You will be positioned with the hip, knee, 
and ankle of the more-affected leg at 90 degrees of flexion. The fatigue task will 
be performed at 30% of your best leg strength test. Visual feedback will be 
provided on a computer monitor. You will perform the task until you can no longer 
generate the needed force (within 5% of the target value for 5 seconds), or you 
say that you want to stop. At every 1 minute interval you will be asked how you 
feel on a scale from 0 to 10. Your required leg position will be monitored by visual 
inspection. Immediately after task failure another strength test with the knee 
extensors will be performed to measure the decline in strength. 
 
tDCS is a non-invasive technique in which a very weak electrical current is applied to 
the head in order to stimulate the brain. For tDCS, we will place rubber electrodes 
soaked in salt water or electrode gel over your scalp and forehead. Therefore, one of 
the electrodes will be placed over your hair, but no additional substances will be put in 
your hair and no additional preparation of the hair will be conducted.  The electrodes will 
be held in place with a head band. A small current will be passed between the 
electrodes.  You may feel some tingling under the electrodes when the current is first 
turned on. The stimulation will last for no longer than 20 min. 
 
To find the right location of electrode on your head we will use transcranial magnetic 
stimulation (TMS).  For application of TMS, a wire coil is held on the scalp. A brief 
electrical current is passed through the coil and creates a magnetic pulse that 
stimulates the brain. You will hear a click and may feel a pulling sensation on the skin 
under the coil and there may be a twitch in muscles of the face, arm or leg. During the 
stimulation, you will be at rest. You will wear a shower cap during the TMS testing and 
marks will be made on the cap to denote positioning of the coil. 
 
 
 
 
 
 
 
 
 

Consent for Fatigue Group 
 
 
 
 
Page 3 of 8 Participant’s initials _______ Date _______  
Version 24July2017 
 
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 EXPIRES: 9/14/2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ARE THERE REASONS WHY I SHOULD NOT TAKE PART IN THIS STUDY? 
 
You should not take part in this study if: 
 
• A relapse of disease symptoms in the last 60 days 
• A condition unrelated to MS that would exacerbate fatigue, such as 
anemia, hypothyroidism, shiftwork-related fatigue, B12 deficiency, 
major sleep disorder, or major depressive disorder 
• Medical diagnosis or condition that  makes participating in exercise 
training dangerous, such as major renal, pulmonary, hepatic, cardiac, 
gastrointestinal, HIV, cancer (other than treated basal cell cancer), other 
neurological disorders, or pregnancy 
• History of heart attack or current diagnosis of cardiovascular disease 
• History of seizure disorders (or on medications known to 
lower seizure threshold), hydrocephalus (buildup of fluid in 
the brain), or diabetes 
• Alcohol dependence or abuse (>2 drinks/day), or present history 
(last six months) of drug abuse 
• History of significant traumatic brain injury or hydrocephalus 
• Pregnancy 
• Recent hospitalization (within the last 3 months) or enforced bed   
   rest/sedentary state. 
• Presence of metal is present or implanted device or metal object that is not safe 
for TMS. 
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS?  

Consent for Fatigue Group 
 
 
 
 
Page 4 of 8 Participant’s initials _______ Date _______  
Version 24July2017 
 
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 EXPIRES: 9/14/2018 
 
It is not possible to identify all potential risks in research procedures, but the 
researcher(s) have taken reasonable safeguards to minimize any known and potential, 
but unknown, risks. 
 
Risks of Having a Body composition (DXA) scan 
 
The risks associated with the DEXA are very low.  The maximum radiation dose you will 
receive in this study is less than 1/1000th of the federal and state occupational whole 
body dose limit allowed to radiation workers (5,000 mrem) (mrem is a unit used to 
measure radiation dosage).  Put another way, the maximum dose from any scan we 
utilize with this DEXA ranges from 1.2 mrem (Whole body scan) to 12.2 mrem (for 
several of the regional scans, such as lumbar, femur, and forearm scans).  The average 
annual background radiation you already receive is at least 620 mrem/year.  The more 
radiation you receive over the course of your life, the more the risk increases of 
developing a fatal cancer or inducing changes in genes.  The radiation in this scan is 
not expected to significantly increase these risks, but the exact increase in such risks is 
not known.  There are no discomforts associated with this procedure. 
 
Risks of tDCS 
tDCS has been conducted on humans and animals for many years and no evidence has 
emerged to suggest that it is harmful or has ever induced a serious side effect. 
However, the safety of tDCS is dependent on current strength, electrode size, and 
stimulation duration. Accordingly, these parameters have been investigated, and safe 
and effective stimulation guidelines have been identified for research studies and in 
clinical practice for tDCS applications involving human subjects. In the several hundred 
studies conducted on humans using tDCS, the only side effects that have been reported 
when proper guidelines are followed are temporary tingling, itching, mild headache, or 
skin redness under the electrodes in some subjects.  
 
In conclusion, the tDCS stimulation parameters in this study are identical to the most 
common in the literature and have been proven to be exceptionally safe and well-
tolerated.  Please let us know immediately if you develop any skin pain or 
discomfort during tDCS. We will monitor you during stimulation and will stop the 
procedure if any problem develops. You may ask to stop the procedure at any time.  
Any effects of tDCS should wear off within 60-90 minutes after the current is stopped.  
 
Risks of TMS 
TMS is a safe, non-invasive brain stimulation technique that can be used for both 
diagnostic and therapeutic procedures. The single pulse TMS techniques that will be 
performed in this study has been used extensively in thousands of research studies and 
on tens of thousands of subjects in the United States and around the world.  Single 
paired pulse TMS technique is considered very safe when accepted guidelines are 
followed and no long-term risks have been reported involving the use of single and 
paired-pulse TMS. For most people, the single pulse stimulation is not painful, but 

Consent for Fatigue Group 
 
 
 
 
Page 5 of 8 Participant’s initials _______ Date _______  
Version 24July2017 
 
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 EXPIRES: 9/14/2018 
occasionally slight discomfort or headache can occur. The headaches go away quickly 
with nonprescription medication. TMS produces a loud clicking sound when a current is 
passed through the stimulation coil. This click can result in ringing in the ear and 
temporary shifts in your ability to determine the pitch and loudness of sounds, if no 
protection is used. In order to prevent this possible side effect, we will ask you to wear 
earplugs that block the noise of the TMS. Hearing damage is possible and one subject 
suffered permanent hearing damage when hearing protection fell out, although this was 
done using repetitive TMS (rTMS). This study does NOT include rTMS or paired 
pulse TMS and only single pulse TMS will be employed in this study (see below). 
Animal and human studies have shown that earplugs or headphones can effectively 
prevent the risk of hearing disturbance due to TMS. Therefore, you will be fitted with 
earplugs during TMS.  If you find the procedure too uncomfortable, you may 
discontinue it at any time.  
 
TMS can interfere with implanted medical devices and will not be done in people who 
have pacemakers, implanted pumps, or stimulators, such as cochlear implants or in 
people who have metal objects inside the eye or skull (dental work such as fillings and 
similar procedures do not pose a risk and are acceptable).  Please inform the 
investigators if you have any of these or known hearing loss. If metal is present or you 
have an implanted device or metal object that is not safe for TMS, you will not be 
allowed to participate.  
 
In general, the risks associated with TMS are very minimal but research has shown that 
there is a very small risk of seizures if repetitive TMS (rTMS) is done with very intense, 
high frequency stimulation or with trains of stimulation separated by a second or less.  
Such intensity, frequency and repetition rate will not be used in this study as the 
study does NOT include rTMS and only single pulse TMS method will be 
employed. Finally, there is no medical risk associated with the surface EMG recordings 
of the muscle responses to TMS.  
 
Risks of Performing Motor Tasks 
 
Generally, the procedures outlined for measuring force and muscle activity during the 
motor tasks are safe.  Nevertheless, there is potential for injury (muscle strain), resulting 
from the maximal contractions.  There is a 0.01% chance of death (in people who have 
heart problems), a 0.02% risk of cardiac arrhythmias that would require you to go the 
hospital (in people with heart problems), and a risk of an increase or decrease in blood 
pressure. 
 
All contractions are voluntary and you can stop immediately if they experience any slight 
pain or discomfort.  Following participation, you may experience some muscle soreness.  
Muscle soreness tends to be more common for individuals who have not exercised 
recently.  Other risk factors may include increased feelings of anxiety and/or stress 
induced by the experiment, which can lead to an increase in heart rate and blood 
pressure.  The EMG electrodes that will be used to measure muscle activity could 

Consent for Fatigue Group 
 
 
 
 
Page 6 of 8 Participant’s initials _______ Date _______  
Version 24July2017 
 
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 EXPIRES: 9/14/2018 
potentially cause skin irritation after removal.  Furthermore, your skin will need to be 
shaved prior to placing the electrodes, which can also cause irritation. 
 
General Risk 
 
Even though the risk is minimal, there is a risk for breach of confidentiality.  Your data 
will be coded to prevent any link to your identity, and any identifying material will be 
locked in a secure filing cabinet.  Furthermore, the potential physical risks of 
participating in the proposed experiments are reasonably small.  The motor 
performance tasks have been used previously by the members of the investigative team 
without complication.   
 
ARE THERE ANY BENEFITS FROM TAKING PART IN THIS STUDY?  
There may be no direct benefit to you associated with this research. This study is 
designed for the researcher to learn more about mobility problems and fatigue in 
persons with MS.  This study is not designed to treat any illness or to improve your 
health.   
 
DO I HAVE TO TAKE PART IN THE STUDY?  
Your participation in this research is voluntary.  If you decide to participate in the study, 
you may withdraw your consent and stop participating at any time. 
 
WHAT WILL IT COST ME TO PARTICIPATE?  
Other than transport to and from the lab, your participation should incur no costs. 
 
WHO WILL SEE THE INFORMATION THAT I GIVE?  
We will keep private all research records that identify you, to the extent allowed by law.  
Your information will be combined with information from other people taking part in the 
study.  When we write about the study to share with other researchers, we will write 
about the combined information we have gathered.  You will not be identified in these 
written materials.  We may publish the results of this study; however, we will keep your 
name and other identifying information private. 
 
We will make every effort to prevent anyone who is not on the research team from 
knowing that you gave us information, or what that information is.  For example, your 
name will be kept separate from your research records and these two things will be 
stored in different places under lock and key.  You should know, however, that there are 
some circumstances in which we may have to show your information to other people.  In 
addition, for funded studies, the CSU financial management team may also request an 
audit of research expenditures. For financial audits, only the fact that you participated 
would be shared, not any research data. We may be asked to share the research files 
with the CSU Institutional Review Board ethics committee for auditing purposes, if 
necessary. 
 
 

Consent for Fatigue Group 
 
 
 
 
Page 7 of 8 Participant’s initials _______ Date _______  
Version 24July2017 
 
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 EXPIRES: 9/14/2018 
 
CAN MY TAKING PART IN THE STUDY END EARLY?  
If you fail to show up to your visits you may be removed from the study. 
 
WILL I RECEIVE ANY COMPENSATION FOR TAKING PART IN THIS STUDY? 
Yes, once you have completed the study you will receive $20.   
 
WHAT HAPPENS IF I AM INJURED BECAUSE OF THE RESEARCH?  
The Colorado Governmental Immunity Act determines and may limit Colorado State 
University's legal responsibility if an injury happens because of this study.  Claims 
against the University must be filed within 180 days of the injury. The research team will 
not cover any injury resulting in this study. You and/or your health insurance will be 
responsible for paying for any study-related injury. 
 
WHAT IF I HAVE QUESTIONS?       
Before you decide whether to accept this invitation to take part in the study, please ask 
any questions that might come to mind now.  Later, if you have questions about the 
study, you can contact the investigator, Dr. Thorsten Rudroff, via phone 970-491-8655 or 
email: Thorsten.rudroff@colostate.edu.  If you have any questions about your rights as a 
volunteer in this research, contact the CSU IRB at:  RICRO_IRB@mail.colostate.edu; 
970-491-1553. We will give you a copy of this consent form to take with you. 
 
WHAT ELSE DO I NEED TO KNOW? 
 
A description of this clinical trial will be available on http://www.ClincialTrials.gov, as 
required by U.S. Law.  This website will not include information that can identify you.  At 
most, the website will include a summary of the results.  You can search this website at 
anytime. 
 
FUTURE STUDIES: 
Would you like to be contacted for future studies that you may be eligible for? Please 
initial:   
 
 
Yes 
 
 
 
No 
 
 
Your signature acknowledges that you have read the information stated and willingly sign 
this consent form.  Your signature also acknowledges that you have received, on the 
date signed, a copy of this document containing    7    pages. 
 
_________________________________________ 
_____________________ 
Signature of person agreeing to take part in the study  
 
 
Date 
 
_________________________________________ 
_____________________ 
Printed name of person agreeing to take part in the study  
Time of Day 
 
_______________________________________  
_____________________ 

Consent for Fatigue Group 
 
 
 
 
Page 8 of 8 Participant’s initials _______ Date _______  
Version 24July2017 
 
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 EXPIRES: 9/14/2018 
Name of person providing information to participant 
 
 
 
Date 
 
_________________________________________    
Signature of Research Staff 

Consent for Strength Group 
 
 
 
 
Page 1 of 7 Participant’s initials _______ Date _______  
Version 06Jun2017  
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 * EXPIRES: 9/14/2018 
Consent to Participate in a Research Study 
Colorado State University 
 
TITLE OF STUDY: Can transcranial direct current stimulation (tDCS) improve 
ambulation and fatigue resistance in people with MS? 
 
PRINCIPAL INVESTIGATORS:   
The principal investigator is a researcher in the Department of Health and Exercise 
Science at Colorado State University: 
 
Thorsten Rudroff, Ph.D., FACSM  
 
 
 
 
HES-INPL@mail.ColoState.EDU   
 
 
970-491-8655 
 
 
 
 
 
 
 
 
 
WHY AM I BEING INVITED TO TAKE PART IN THIS RESEARCH?  
You are an adult aged between 30 and 60 years of age, and you were diagnosed with 
Multiple Sclerosis. 
 
WHO IS DOING THE STUDY?  
Dr. Rudroff and his graduate students John Kindred, Nathan Ketelhut, and Felix Proessl 
are performing the study in the Integrative Neurophysiology Laboratory. 
 
WHAT IS THE PURPOSE OF THIS STUDY? 
The purpose of this study is to determine if a single session of tDCS can increase the 
muscle strength of the more affected leg in people with MS. 
 
WHERE IS THE STUDY GOING TO TAKE PLACE AND HOW LONG WILL IT LAST?  
The study will take place in the Integrative Neurophysiology Laboratory in the 
Department of Health and Exercise Science, on the Colorado State University campus. 
The study will run for approximately 12 months. You will take part in the study for 
approximately a total of 3 hours over the space of two weeks. 
 
WHAT WILL I BE ASKED TO DO?  
You will be asked to participate in two sessions on two different days separated by no 
less than 7 days.  Each visit will last approximately 90min. 
 
If you participate in this study you will perform strength tests of your leg muscles in 
association with 1 of 2 intervention protocols involving tDCS application (BEFORE and 
SHAM) with each intervention protocol being performed in a separate session on a 
different day.  Thus, in one session you will receive tDCS before the strength test, 
whereas in another session you will receive sham tDCS before the strength test. 
 
Upon arrival to the INPL the investigators will explain the protocol procedures and 
receive signed informed consent from you.  
 

Consent for Strength Group 
 
 
 
 
Page 2 of 7 Participant’s initials _______ Date _______  
Version 06Jun2017  
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 * EXPIRES: 9/14/2018 
- 
Questionnaires: You will fill out to questionnaires relating to fatigue and 
depression. 
- 
Body Composition: We will perform a Dual-Energy X-Ray Absorptiometry (DXA) 
scan on you. A very small amount of X-Rays will pass through your body and 
allow us to measure the amount of muscle, fat, and bone you have. 
- 
Leg Strength: The maximal strength of each leg will be measured by having you 
perform a series of maximal effort knee extension, knee flexion, plantar/dorsi-
flexion trials.  This will be performed one leg at a time up to five times. The 
activity of your muscles will be measured during this task by placing a series of 
electrodes on the skin of your legs. 
- 
6 Minute Walk Test: After completion of the strength testing we will see how far 
you can walk in 6 minutes. You will be allowed to stop and rest as needed. 
 
tDCS is a non-invasive technique in which a very weak electrical current is applied to 
the head in order to stimulate the brain. For tDCS, we will place rubber electrodes 
soaked in salt water or electrode gel over your scalp and forehead. Therefore, one of 
the electrodes will be placed over your hair, but no additional substances will be put in 
your hair and no additional preparation of the hair will be conducted.  The electrodes will 
be held in place with a head band. A small current will be passed between the 
electrodes.  You may feel some tingling under the electrodes when the current is first 
turned on. The stimulation will last 10 minutes. 
 
To find the right location of electrode on your head we will use transcranial magnetic 
stimulation (TMS).  For application of TMS, a wire coil is held on the scalp. A brief 
electrical current is passed through the coil and creates a magnetic pulse that 
stimulates the brain. You will hear a click and may feel a pulling sensation on the skin 
under the coil and there may be a twitch in muscles of the face, arm or leg. During the 
stimulation, you will be at rest. You will wear a shower cap during the TMS testing and 
marks will be made on the cap to denote positioning of the coil. 

Consent for Strength Group 
 
 
 
 
Page 3 of 7 Participant’s initials _______ Date _______  
Version 06Jun2017  
 
CSU#: 16-6856H 
APPROVED: 9/15/2017 * EXPIRES: 9/14/2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ARE 
THERE 
REASONS WHY I SHOULD NOT TAKE PART IN THIS STUDY? 
You should not take part in this study if: 
• A relapse of disease symptoms in the last 60 days 
• A condition unrelated to MS that would exacerbate fatigue, such as 
anemia, hypothyroidism, shiftwork-related fatigue, B12 deficiency, 
major sleep disorder, or major depressive disorder 
• Medical diagnosis or condition that  makes participating in exercise 
training dangerous, such as major renal, pulmonary, hepatic, cardiac, 
gastrointestinal, HIV, cancer (other than treated basal cell cancer), other 
neurological disorders, or pregnancy 
• History of heart attack or current diagnosis of cardiovascular disease 
• History of seizure disorders (or on medications known to 
lower seizure threshold) 
• Hydrocephalus (buildup of fluid in the brain) 
• Alcohol dependence or abuse (>2 drinks/day), or present history 
(last six months) of drug abuse 
• History of significant traumatic brain injury or hydrocephalus 
• Pregnancy 
• Recent hospitalization (within the last 3 months) or enforced bed   
   rest/sedentary state. 
• Presence of metal is present or implanted device or metal object that is not safe 
for TMS. 
• Presence of holes or fissures of the cranial bones 
 
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS?  

Consent for Strength Group 
 
 
 
 
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It is not possible to identify all potential risks in research procedures, but the 
researcher(s) have taken reasonable safeguards to minimize any known and potential, 
but unknown, risks. 
 
Risks of Having a Body composition (DXA) scan 
The risks associated with the DEXA are very low.  The maximum radiation dose you will 
receive in this study is less than 1/1000th of the federal and state occupational whole 
body dose limit allowed to radiation workers (5,000 mrem) (mrem is a unit used to 
measure radiation dosage).  Put another way, the maximum dose from any scan we 
utilize with this DEXA ranges from 1.2 mrem (Whole body scan) to 12.2 mrem (for 
several of the regional scans, such as lumbar, femur, and forearm scans).  The average 
annual background radiation you already receive is at least 620 mrem/year.  The more 
radiation you receive over the course of your life, the more the risk increases of 
developing a fatal cancer or inducing changes in genes.  The radiation in this scan is 
not expected to significantly increase these risks, but the exact increase in such risks is 
not known.  There are no discomforts associated with this procedure. 
 
Risks of tDCS 
tDCS has been conducted on humans and animals for many years and no evidence has 
emerged to suggest that it is harmful or has ever induced a serious side effect. 
However, the safety of tDCS is dependent on current strength, electrode size, and 
stimulation duration. Accordingly, these parameters have been investigated, and safe 
and effective stimulation guidelines have been identified for research studies and in 
clinical practice for tDCS applications involving human subjects. In the several hundred 
studies conducted on humans using tDCS, the only side effects that have been reported 
when proper guidelines are followed are temporary tingling, itching, mild headache, or 
skin redness under the electrodes in some subjects.  
 
In conclusion, the tDCS stimulation parameters in this study are identical to the most 
common in the literature and have been proven to be exceptionally safe and well-
tolerated.  Please let us know immediately if you develop any skin pain or 
discomfort during tDCS. We will monitor you during stimulation and will stop the 
procedure if any problem develops. You may ask to stop the procedure at any time.  
Any effects of tDCS should wear off within 60-90 minutes after the current is stopped.  
 
Risks of TMS 
TMS is a safe, non-invasive brain stimulation technique that can be used for both 
diagnostic and therapeutic procedures. The single pulse TMS techniques that will be 
performed in this study has been used extensively in thousands of research studies and 
on tens of thousands of subjects in the United States and around the world.  Single 
paired pulse TMS technique is considered very safe when accepted guidelines are 
followed and no long-term risks have been reported involving the use of single and 
paired-pulse TMS. For most people, the single pulse stimulation is not painful, but 
occasionally slight discomfort or headache can occur. The headaches go away quickly 
with nonprescription medication. TMS produces a loud clicking sound when a current is 
passed through the stimulation coil. This click can result in ringing in the ear and 

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temporary shifts in your ability to determine the pitch and loudness of sounds, if no 
protection is used. In order to prevent this possible side effect, we will ask you to wear 
earplugs that block the noise of the TMS. Hearing damage is possible and one subject 
suffered permanent hearing damage when hearing protection fell out, although this was 
done using repetitive TMS (rTMS). This study does NOT include rTMS or paired 
pulse TMS and only single pulse TMS will be employed in this study (see below). 
Animal and human studies have shown that earplugs or headphones can effectively 
prevent the risk of hearing disturbance due to TMS. Therefore, you will be fitted with 
earplugs during TMS.  If you find the procedure too uncomfortable, you may 
discontinue it at any time.  
 
TMS can interfere with implanted medical devices and will not be done in people who 
have pacemakers, implanted pumps, or stimulators, such as cochlear implants or in 
people who have metal objects inside the eye or skull (dental work such as fillings and 
similar procedures do not pose a risk and are acceptable).  Please inform the 
investigators if you have any of these or known hearing loss. If metal is present or you 
have an implanted device or metal object that is not safe for TMS, you will not be 
allowed to participate.  
 
In general, the risks associated with TMS are very minimal but research has shown that 
there is a very small risk of seizures if repetitive TMS (rTMS) is done with very intense, 
high frequency stimulation or with trains of stimulation separated by a second or less.  
Such intensity, frequency and repetition rate will not be used in this study as the 
study does NOT include rTMS and only single pulse TMS method will be 
employed. Finally, there is no medical risk associated with the surface EMG recordings 
of the muscle responses to TMS.  
 
Risks of Performing Motor Tasks 
Generally, the procedures outlined for measuring force and muscle activity during the 
motor tasks are safe.  Nevertheless, there is potential for injury (muscle strain), resulting 
from the maximal contractions.  There is a 0.01% chance of death (in people who have 
heart problems), a 0.02% risk of cardiac arrhythmias that would require you to go the 
hospital (in people with heart problems), and a risk of an increase or decrease in blood 
pressure. 
 
All contractions are voluntary and you can stop immediately if they experience any slight 
pain or discomfort.  Following participation, you may experience some muscle soreness.  
Muscle soreness tends to be more common for individuals who have not exercised 
recently.  Other risk factors may include increased feelings of anxiety and/or stress 
induced by the experiment, which can lead to an increase in heart rate and blood 
pressure.  The EMG electrodes that will be used to measure muscle activity could 
potentially cause skin irritation after removal.  Furthermore, your skin will need to be 
shaved prior to placing the electrodes, which can also cause irritation. 
 
General Risk 

Consent for Strength Group 
 
 
 
 
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Even though the risk is minimal, there is a risk for breach of confidentiality.  Your data 
will be coded to prevent any link to your identity, and any identifying material will be 
locked in a secure filing cabinet.  Furthermore, the potential physical risks of 
participating in the proposed experiments are reasonably small.  The motor 
performance tasks have been used previously by the members of the investigative team 
without complication.   
 
ARE THERE ANY BENEFITS FROM TAKING PART IN THIS STUDY?  
There may be no direct benefit to you associated with this research. This study is 
designed for the researcher to learn more about mobility problems and fatigue in 
persons with MS.  This study is not designed to treat any illness or to improve your 
health.   
 
DO I HAVE TO TAKE PART IN THE STUDY?  
Your participation in this research is voluntary.  If you decide to participate in the study, 
you may withdraw your consent and stop participating at any time. 
 
WHAT WILL IT COST ME TO PARTICIPATE?  
Other than transport to and from the lab, your participation should incur no costs. 
 
 
 
WHO WILL SEE THE INFORMATION THAT I GIVE?  
We will keep private all research records that identify you, to the extent allowed by law.  
Your information will be combined with information from other people taking part in the 
study.  When we write about the study to share with other researchers, we will write 
about the combined information we have gathered.  You will not be identified in these 
written materials.  We may publish the results of this study; however, we will keep your 
name and other identifying information private. 
 
We will make every effort to prevent anyone who is not on the research team from 
knowing that you gave us information, or what that information is.  For example, your 
name will be kept separate from your research records and these two things will be 
stored in different places under lock and key.  You should know, however, that there are 
some circumstances in which we may have to show your information to other people.  
We may be asked to share the research files with the CSU Institutional Review Board 
ethics committee for auditing purposes, if necessary. 
 
CAN MY TAKING PART IN THE STUDY END EARLY?  
If you fail to show up to your visits you may be removed from the study. 
 
WILL I RECEIVE ANY COMPENSATION FOR TAKING PART IN THIS STUDY? 
There is no compensation for this study. 
 
WHAT HAPPENS IF I AM INJURED BECAUSE OF THE RESEARCH?  

Consent for Strength Group 
 
 
 
 
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The Colorado Governmental Immunity Act determines and may limit Colorado State 
University's legal responsibility if an injury happens because of this study.  Claims 
against the University must be filed within 180 days of the injury. The research team will 
not cover any injury resulting in this study. You and/or your health insurance will be 
responsible for paying for any study-related injury. 
 
WHAT IF I HAVE QUESTIONS?       
Before you decide whether to accept this invitation to take part in the study, please ask 
any questions that might come to mind now.  Later, if you have questions about the 
study, you can contact the investigator, Dr. Thorsten Rudroff, via phone 970-491-8655 or 
email: Thorsten.rudroff@colostate.edu.  If you have any questions about your rights as a 
volunteer in this research, contact the CSU IRB at:  RICRO_IRB@mail.colostate.edu; 
970-491-1553. We will give you a copy of this consent form to take with you. 
 
WHAT ELSE DO I NEED TO KNOW? 
 
A description of this clinical trial will be available on http://www.ClincialTrials.gov, as 
required by U.S. Law.  This website will not include information that can identify you.  At 
most, the website will include a summary of the results.  You can search this website at 
anytime. 
 
 
 
FUTURE STUDIES: 
Would you like to be contacted for future studies that you may be eligible for? Please 
initial:   
 
 
Yes 
 
 
 
No 
 
 
Your signature acknowledges that you have read the information stated and willingly sign 
this consent form.  Your signature also acknowledges that you have received, on the 
date signed, a copy of this document containing    7     pages. 
 
_________________________________________ 
_____________________ 
Signature of person agreeing to take part in the study  
 
 
Date 
 
_________________________________________ 
_____________________ 
Printed name of person agreeing to take part in the study  
Time of Day 
 
_______________________________________  
_____________________ 
Name of person providing information to participant 
 
 
 
Date 
 
_________________________________________    
Signature of Research Staff 

Title: Can transcranial direct current stimulation improve ambulation and fatigue resistance in  
people with MS?  
NCT #: NCT02987621  
Document date: 08/24/2017 
Statistical analysis:  
Separated by a minimum of 7 days, participants performed experimental protocol twice once with tDCS 
and once with Sham in a counterbalanced order. A repeated measures ANOVA (condition x time) and 
paired t-tests were used to compare Sham vs. tDCS. Data are reported as means (tDCS vs Sham) plus or 
minus the standard deviations.