Building Strength Through Rehabilitation for Heart Failure Patients
Phase: NA
Conditions: Heart Failure
Sponsor: Indiana University

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Building strength through rehabilitation for heart failure patients- 
BISTRO STUDY 
 
 
 
Principal Investigator: 
 
Christine Haedtke, Ph.D., RN, PCCN 
 
Assistant Professor, Department of Community and Health Services 
I.U. School of Nursing 
 
 
 
 
 
 
Sub-Investigators:   
 
Peter Pang, M.D., MS 
 
Susan Pressler, Ph.D., RN, FAAN, FAHA 
 
Jeffrey Kline, M.D. 
 
Stuart Warden, PhD, PT, FACSM  
 
 
 
 
 
 
 

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Table of contents 
 
 
Section 1:   Background and Significance  
Section 2:   Rationale and Specific Aims 
Section 3:   Inclusion and Exclusion Criteria 
Section 4:   Enrollment and Randomization 
Section 5:   Study Procedures 
Section 6:   Reporting of Adverse Events or Unanticipated Problems involving Risk to 
participants or others 
Section 7:   Study Withdrawal/Discontinuation 
Section 8:   Statistical considerations 
Section 9:   Privacy and Confidentiality Issues 
Section 10: Follow-up and Record Retention 
Section 11: References 
Section 12: Appendix 
 
 
Section 12A: SOP for ActivPal 
 
 
Section 12B: SOP for EMPI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Section 1: Background and Significance 
 
Heart Failure (HF) has become one of the most discussed chronic conditions due 
to its high incidence, increasing prevalence, and treatment costs. Benjamin, et al. 
estimated 6.5 million people in the U.S. have HF and 915,000 new cases are diagnosed 
each year.11 This number is projected to rise to 8 million by 2030 with direct and indirect 
costs rising from $39.2 billion to $70 billion.12,13 With the increasing prevalence and 
rising costs of HF, consideration of ways we can decrease the negative effects become 
essential. One approach to improving outcomes is by assisting patients with HF to 
exercise.  
Of those admitted to the hospital for heart failure, lower extremity weakness was 
common with 40% of them unable to rise from a chair without using the arm rests, and 
profound weakness with 6 minute walk distance of 178 meters the day before being 
discharged home.14  Due to the profound weakness, interventions that improve strength 
without causing further fatigue is critical to improving outcomes for this population. 
Skeletal muscle function has been found to deteriorate in HF patients, when 
compounded in muscle wasting that is common in any patient admitted to the hospital, 
additional interventions are needed for this very fragile group.  
  Exercise has many personal benefits for patients with HF, such as improvement 
in exercise capacity, skeletal muscle strength and endurance, endothelial function, 
skeletal muscle chemistry and decreased sympathetic activity.15,16  Other probable 
benefits include: increased cardiac output, improved left ventricular characteristics and 
skeletal muscle histology, decreased plasma neurohormones, and an anti-inflammatory 
effect.15,16  All of these benefits should decrease the need for hospitalizations and extra 
clinic visits along with improving patient’s quality and satisfaction of their care in addition 
to improving their quality of life.15  
Patients have difficulties adhering to the exercise portion of most study 
protocols.4-6 Further compounding the problem of getting patients to exercise is the fact 
that many patients with HF are not willing to begin exercising or they discontinue the 
exercise regimen once they start.17 Pain, shortness of breath and poor activity tolerance 
are common in those with HF and may help to explain the resistance to exercise by 
patients with HF.2,18 Considering the extra attention patients of exercise trials receive to 
encourage them to stay in study protocols, the finding that the majority are still unable to 
meet the exercise requirements indicates that more research needs to be done to 
improve adherence.     
One way to improve patients with HF poor activity tolerance and thus adherence 
is by using electrical stimulation to increase muscle strength and endurance.  
Neuromuscular electrical stimulation (NMES) has been shown to increase muscle 
strength and endurance in many patient populations including those with HF.10 In a 
systematic review examining the effect of NMES on patients with chronic diseases, 
those with HF found improvements in peak workload, oxygen uptake, muscle strength, 
health status, exercise duration, and fatigue.10 The benefits of NMES can also be found 
in the capillary beds after only two days of use with gradual increases in the number of 
capillaries with a plateau at four weeks of therapy.19 Improved venous and lymph return 
decreases edema and the stimulation reduces vasoconstriction by increasing nitric 
oxide production. With these improvements, muscles show less fatigue and better 

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physical performance due to the increase in blood in the muscle area and thus 
improved removal of metabolic wastes.19  
Fortunately exercise and NMES can improve local blood flow, exercise capacity 
and muscle mass.7 Banerjee found an average improvement of 0.24L in peak VO2 when 
using NMES to increase strength in healthy sedentary adults.8 Maillefert found an 
increase in exercise capacity and muscle volume when low frequency NMES was used 
in those with HF.9 While this was a small sample, peak VO2 increased 2.4 ml/kg/min, 6-
minute walk test (6MWT) saw an improvement of 40 meters.  Maillefert found low 
frequency NMES was safe, well tolerated and effective.9 In the systematic review by 
Sillen, in the nine HF studies using NMES as an intervention, researchers reported 
NMES was safe, but the protocol’s varied widely and some of the patients dropped out 
due to discomfort.10  
The hypothesis is that by using NMES, patients with HF will, in part, reverse the 
muscle wasting that occurs with HF and actually increase muscle mass and 
strength.20,21 With this increase in muscle, it is expected that patients will become more 
active, thus reversing the downward spiral that has been observed with doing less 
leading to less ability.  One of the key factors in choosing this modality is that patients 
only need to apply the electrodes to their thighs and then sit back and let the machine 
do the work. Patients will be instructed to also add active quadriceps muscle contraction 
during the passive NMES contraction to decrease any discomfort and also to aid the 
building of muscle.22 Thus, NMES is used as the first step in an exercise program that is 
tailored for this very difficult population in order to improve exercise initiation, 
adherence, and sustained practice. Bruckenthal suggests in order to improve attitudes 
and adherence towards exercise by those with HF we need to increase the 
entertainment value or likeability of the options.23 Being able to begin an exercise 
program without getting short of breath or having to invest a lot of energy in a population 
that is highly fatigued and short of breath, should improve the likeability and practicality 
of the option. With the increase in strength the patient may begin to feel some success 
which may then lead to increases in other activities leading to an overall improvement in 
exercise tolerance, improved functional ability, quality of life, and participation formal 
exercise programs.  
 
Innovation 
 
NMES uses a lightweight, battery powered electrical stimulation unit (which is 
attached to the patient via self-adhesive electrodes) to produce a controlled contraction 
of the underlying muscle. It can be self-administered at home while the participant is 
passively sitting or lying down thus decreasing the demands of exercise while still 
allowing the participant many of the same benefits.24 Previous studies using NMES and 
those with HF have shown benefit, but, the protocols have varied widely, the outcome 
variables of interest have also varied widely, in addition there was no further formal 
exercise program encouraged upon completion of the study. The innovation of this 
study is that all the previous knowledge gained has been merged into a protocol that is 
double blinded, patient centered protocol to improve compliance, tolerability, and ease 
of use. Also, this proposal focuses on NMES being used as the stepping stone to 
enable those with HF to participate in structured exercise program.  

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Section 2:   Rationale and Specific Aims Research Design and Methods 
 
The purpose of this double blinded, randomized, controlled, longitudinal study is 
to determine if NMES will increase muscle mass and strength, decrease sedentary time, 
and improve HF symptoms and exercise capacity, thus improving quality of life in 
patients with HF. It is hypothesized that with this increase in muscle mass, patients will 
improve overall exercise tolerance and capacity. In addition, after the intervention 
patients will be better able to tolerate an exercise program thus improving adherence to 
exercise recommendations. After 6 weeks of intervention, patients will be encouraged to 
participate in a formalized exercise program.  
Specific Aim 1:  Test the effect of NMES on muscle mass and strength in patients 
with HF. We will use DXA and dynamometer to evaluate this aim. We hypothesize that 
NMES will increase lean muscle mass and decrease fat mass of the thighs. Also that 
strength and force of the thighs will improve.  
Specific Aim 2: Evaluate the effect of NMES on exercise capacity and activity in 
patients with HF. We will use 6-minute walk test to evaluate exercise capacity and 
ActivePal accelerometer to evaluate activity levels. We hypothesize that exercise 
capacity and the amount of daily activity will increase while sitting/lying time will 
decrease from pre intervention to post intervention time points.  
Specific Aim 3:  Assess the effect of NMES on HF symptoms and health-related 
quality of life (HRQOL). We will use the Memorial Symptom Assessment Scale-HF and 
Minnesota Living with Heart Failure Questionnaire (MLHFQ) to evaluate this aim. We 
hypothesize that HRQOL will increase while HF symptoms decrease. 
Specific Aim 4: Evaluate the effect of NMES on enrollment and utilization of a 
formalized exercise program. We hypothesize that patients in the NMES group will be 
more likely to participate in a formalize exercise plan following the intervention than the 
sham group. 
We will use a double blinded, randomized controlled longitudinal study design to 
determine if NMES will increase muscle mass and strength, decrease sitting and lying 
time, and improve HF symptoms and exercise capacity thus improving likelihood of 
engagement with a structured exercise program. Patients will be randomized to either 
intervention that includes NMES or to a sham/wait list control group.  
 
Importance of the Knowledge to be gained 
 
Research has shown that patients with HF see significant improvement in their 
HF symptoms, decrease hospitalizations, and find improvement in their overall health 
when they follow a prescribed exercise regimen. Many patients are not willing or able to 
begin exercising or discontinue the exercise regimen once they do start one due to high 
levels of fatigue and shortness of breath due to muscle wasting that occurs with HF. 
Having a lower starting point (starting with passive NMES) for exercise and building 
muscles up before enrolling in a cardiac rehabilitation program to meet the current 
exercise recommendations will likely improve the success for patients in being able to 
exercise.  It is expected that all patients will benefit from a formalized exercise program 
regardless of NMES or Sham randomized group.  

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The data collected in this study will be used to prepare a NIH RO1 application, 
which will launch my independent program of research. Using NMES to improve 
exercise use in patients with HF is of specific interest to the NIH due to all the potential 
improvements previously discussed. There is a great potential for extramural funding for 
development of non-pharmacologic interventions that maintain/improve independence, 
increase quality of life, decrease hospitalizations, and improve patient outcomes. This 
study will add to the science by determining if NMES can be used as a stepping stone 
for enrollment into formalized exercise rehabilitation program, or as an approach for 
those who are unable to exercise. 
 
 
Section 3:   Inclusion and Exclusion Criteria 
 
Inclusion criteria 
 
Adult patients with a recent hospitalization or clinic visit for heart failure, (ICD-9 
428; ICD-10 I50) and one of the following: BNP >400 OR NT-proBNP>900 (If renal 
dysfunction >1200) OR Echo showing myocardial remodeling, dilation, hypertrophy, or 
dysfunction will be included in this study. In addition patients must live at home, and not 
regularly exercise (10 minutes or more a day of exercise most days of the week for the 
past week).25 Sedentary patients are the focus of this intervention because they would 
most likely see significant improvement with the intervention.  
 
Exclusion criteria 
 
 Patients, who have undertaken cardiac rehab within the 12 months prior to 
enrollment, have a cognitive or other impairment which prevents accurate application of 
intervention or inability to provide informed consent, End Stage Renal Disease or 
receiving mechanical ventilation, receiving non-approved FDA-investigational agents or 
devices, has received a heart transplant, a destination Ventricular Assist Device  
(LVAD), pacemaker, or implantable cardiac device, previously used NMES 
(Neuromuscular electrical stimulation) or TENS (Transcutaneous electrical nerve 
stimulation) or Uncontrolled arrhythmia’s or 3 degree AV heart block, are unable to 
correctly apply and operate the device even after instruction (as determined by the 
Research Assistant), those with wounds over area of proper placement of electrodes, or 
those who are unable to speak and write English. Women who are pregnant or planning 
to become pregnant.  
 
Children will not be included in this study. Although HF can occur in all ages, it is 
primarily a disorder of the elderly. In addition the causes of HF in children is very 
different than adults.  
 
Section 4:   Enrollment and Randomization 
Patients who meet eligibility criteria will be referred to the investigator or the 
research assistant by cardiology, heart failure, or emergency room providers during 
their routine evaluation of patients eligible for participation in other heart failure research 
studies through the medical record system. In addition, a clinical research systems 

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request has been made to allow for notification to the PI the identification all heart 
failure patients admitted to the hospital so the PI or RA can screen for eligibility. In 
addition, Dr. Susan Pressler will release names and contact information for previous 
participants in her HF study to the PI if the participant has previously indicated they 
would like to be contacted for future research studies for screening to determine 
eligibility to participate in this study. The patient will then be contacted by a BISTRO 
team member for a full explanation of the study and determine interest in participating. If 
they are interested and are also willing to participate in the FIT Core study (IRB 
#170755085), an appointment for follow up discussion and possible consenting for both 
studies) will then be set up for the following week or two. At which time they will come to 
the school of nursing for final consideration, potential consenting, begin data collection.   
In order to ensure that the two groups are comparable between treatment and 
sham interventions, the participants will be randomized according to gender. 
Randomization via minimization will be used in order to avoid an unbalanced number of 
women in the two comparison groups due to chance.26 A file of the computer-generated 
random assignments will be kept by the research assistant so the PI/data collector 
remains blinded in a protected Box Health account.  
 
Section 5:   Study Procedures 
Intervention and Sham/Wait List Control Conditions  
 
The PI will collect all baseline data before the participant is randomized to the 
intervention or sham/wait list control group. In order to ensure rigor, patients and PI are 
blinded to study assignment. The intervention/sham will be set-up by the RA and will be 
collected after the PI leaves the department so those collecting data will not know which 
group the participant has been/will be participating in. The RA who is trained in both 
NMES and Sham intervention will then look at the randomization schedule, and set up 
and train the participants on equipment use after the data has been collected.27 Once 
trained, participants will be contacted via phone weekly by the RA who initially trained 
them (in order to maintain blinding) to determine if participants are following protocol 
and placement as taught, if the participant is tolerating the intervention, skin condition 
under the electrodes, and if there are any questions or problems with the machine. The 
RA applying the intervention will not have any part in the data collection of the rest of 
the measurements (other than adherence, tolerance and problems with equipment).  
The Empi Continuum electrotherapy system made by Empi, Inc. (Clear Lake 
South Dakota) is chosen for NMES in this study because it is already available to the PI, 
it has both the intervention and sham settings, and is able to track adherence (total 
number of sessions, total session time, average session time, average intensity). Each 
machine will be calibrated before use for each participant and also checked with each 
return visit. The output of the stimulator will be checked with an oscilloscope to ensure 
consistency between the current reading on the stimulator and the actual current output 
every time the participant returns. NMES will be set up with the machine on 
simultaneous large muscle atrophy setting with 500 ohm with peak of 50 volts, the “self-
adhesive electrodes positioned on the thighs approximately 5 cm below the inguinal fold 
and 3 cm above the upper patella border” as described by Gobbo.28 When applying the 
stimulation, the intensity will be gradually increased from an intermittent tingling until a 

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gentle pumping sensation is felt.  Participants will direct the amount of stimulation 
acceptable on both thighs to improve acceptance of the modality.10,24,29-31 To assist 
better tolerance large electrodes (2x4) will be used and participants will also be 
instructed to be in a seated position with chair close to the wall so that their leg is 90-
degree angle and then push against the wall to decrease any uncomfortable feeling 
during the contraction.  For the Sham group, electrodes will follow the same landmarks, 
but the stimulation will only increase to an intermittent tingling sensation with the 
machine setting on TENS instead of NMES which is not enough to make noticeable 
changes in muscle mass or circulation.32 Participants in both groups will be given written 
instructions and contact information of the person (RA) to contact should there be any 
problems or concerns with the intervention. All participants will do a return 
demonstration to assure proper knowledge has been gained. Adherence to the study 
protocol will be determined by the amount of time the EMPI machine records that it was 
used, the intensities utilized along with verbal verification during the weekly phone calls.  
NMES Protocol Summary 
• 5 sessions per week for 6 weeks done independently at home, with 15 minutes 
per session (15 stimulations per day/session, 15 seconds stimulation on, 15 
seconds recovery time) to both legs. 
• Intervention group only: We expect the participant to develop tolerance to the 
treatment and thus increase the intensity of the NMES over time. 
• At the end of the trial, the participants will return to have all measures repeated. 
Sham group will then be offered the active treatment. In previous HF studies 
(non-NMES) done by the mentor of this grant, no participants have accepted the 
offer of the intervention after completion of the sham/control so this number is 
expected to be very small.  
• Participants will be encouraged to begin a formalized exercise plan such as 
Silver Sneakers, a home based cardiac rehabilitation or institutional cardiac 
rehabilitation program. 
• Finally, 3 months after the intervention/sham was completed participants will 
return one final time to have all measures repeated to allow for evaluation of 
activity levels following completion of the intervention.  
Retention 
 
Participants will be told prior to enrolling in the study that they could be 
randomized to the sham treatment group, and if so, they will be given the opportunity to 
participate in the NMES protocol after completing the sham intervention. Individualized 
calendars will be provided to participants to assist in reminding them when which 
assessment is scheduled. Participants in both groups will be provided the same 
compensation of $50 for each visit where physical data are collected, $10 for each 
weekly phone call ($60) with RA to assess adherence/problems. Total money paid to 
participants completing all components of participation will be $210.   
• Payment 1: $50 for baseline measures (paid upon return of ActivPal, paid via 
voucher checks sent in the mail) 
• Payment 2-6: $10 for phone call/verification (paid weekly following the phone call 
via voucher checks sent in the mail) 

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• Payment 5: $50 for post intervention measures (paid upon return of ActivPal, 
after the second physical testing visit-mailed to participant)   
• Payment 6: $50 for Final post intervention measures (paid upon return of 
ActivPal after the third physical testing visit-mailed to participant) 
If participants fail to return the equipment they will not receive the payment scheduled 
for that visit. 
 
Instruments and Measures 
1. Dual-energy x-ray absorptiometry (DXA) will be used to determine if there is a 
measurable change in fat mass and skeletal muscle mass as a result of NMES 
intervention (specific aim 1).  Other studies have found an increase in muscle strength 
but muscle mass was not measured with DXA. DXA is chosen because it is quick (10-
15 minutes), relatively cheap (compared to CT), analysis is straight forward and patients 
are more accepting of DXA procedures than CT.33 Hologic Discovery-W densitometer is 
the DXA machine we will be using with Apex software version 2.3. Calibration will be 
conducted every day a participant is scheduled to come in and weekly scanning of 
manufacturer supplied supine phantom will also be ran to determine that no 
instrumentation drift has occurred. Coefficients of variance were reported to be between 
1-3% thus showing this machine to have an excellent precision.33 DXA is the gold 
standard in the measurement of body composition.34 Total and segmental (bilateral 
upper leg) body composition will be assessed according to the differential degree of 
photon attenuation at two levels of energy as described by Steiner.35 
2. Strength Assessment will be done using a Biodex 
isokinetic dynamometer (Biodex Medical Systems, 
Shirley, NY) (specific aim 1). The load cell will be 
calibrated prior to testing daily using manufactures 
guidelines. The patient will be seated with padded straps 
placed across their chest and thigh to reduce movement 
of the trunk and thigh during testing (see image to right). 
The knee will be flexed to 90° following the protocol 
described by Toonstra.36 An inelastic strap attached to 
the testing arm of the instrument will be placed around 
the leg just above the ankle. Participants will be asked to 
tighten their thigh and straighten their knee as hard as 
they can. The arm of instrument will allow the knee to be straightened at 60 degree per 
second, with the instrument’s load cell measuring force. Participants will be given 5 
minutes to familiarize themselves with the device and perform practice trials prior to 
testing. When instructed, subjects will kick (tighten their thigh muscle and try to 
straighten their knee as hard as they can against the testing machine). This will be 
performed 5 times on the dominate leg with a 120 second rest period between each set 
of 3 attempts. The second part of the test includes kicking 50 times in a row. Following 
the 50 kicks participants will be given 30 seconds to rest, then asked to repeat 3 kicks 
for a series of 5 times. The leg strength test will take approximately 40 minutes to 
complete. These testing procedures have yielded excellent reliability in healthy 
population with ICC = .92 and minimal detectable change with 95% confidence of .42 
Nm.36 

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3. The 6-min walk test (6MWT) estimates the person’s ability to perform everyday 
activities by measuring the distance walked in a set time period.37 It will be used to 
measure exercise capacity, specific aim 2.38 Participants will be allowed use of an 
assistive device and will be instructed to move as quickly as they feel safe and 
comfortable over the 100-meter course for 6 minutes. As per the protocol, participants 
will be allowed to stop and rest if necessary. This test is recommended by the American 
Thoracic Society for patients with moderate to severe heart or lung disease.39 A 
clinically significant difference due to treatment effect has been established as the 
increase in distance walked must be at least 5% higher than baseline.40 A high degree 
of concordance (80%) for positive or neutral response to exercise interventions for HF 
treatment accurately reflect clinical effects induced by the intervention.40-42  
 
4. ActivPal4 is an accelerometer that also has an inclinometer built in to differentiate 
between lying/sitting, standing and walking. It will be used to measure physical activity 
levels (specific aim 2). Analysis of data is straight forward as data are recorded in 
minutes and seconds of time spent sitting/lying, standing, moving, and actual number of 
steps taken. Patients will be instructed to wear the ActivPal for 7 days continuously 
during each time point.  It is worn on the thigh and placed under a waterproof “bandage” 
after having the skin protected with skin prep.  This allows the patient to put it on and 
forget about it even in the shower (not swimming or prolonged underwater activity) to 
also assist in complete data being recorded. Reliability was found to be 0.99 when 
compared with direct (camera recorded) observation for sitting and transitioning from 
sitting to standing.43 The correlation between the ActivPal and direct observation of 
position and number of step taken was = 0.94.44 Lastly, the ActivPal was tested in 
sedentary older adults with impaired function and found to agree 100% of the time with 
direct observation with sitting and standing time.45  
5. Use the Memorial Symptom Assessment Scale-Heart Failure (MSAS-HF) is a 
measure of HF symptoms, that will be used (specific aim 3). MSAS-HF is a measure of 
32 heart failure symptoms (27 physical and 5 psychological), which rates each symptom 
on the basis of presence or absence, and if present, the frequency, severity and level of 
distress the symptom causes over the past 7 days.46  Administration takes 
approximately 5-15 minutes after going through instructions, depending on the number 
and severity of the symptoms, and can be interviewer or self-administered. There is an 
average score for each symptom, and subscales in HF, physical, and psychological 
symptoms.46 Reliability of burden scores in each subscale was examined using 
Cronbach’s α, which were 0.80–0.87 for the physical symptom subscale; 0.83–0.91 for 
the psychological symptom subscale; and 0.73–0.85 for the HF symptom subscale.47,48 
6. Minnesota Living with Heart Failure Questionnaire (MLHFQ) is a measure of HF 
quality of life and reflects the effect of HF and treatments for HF on an individual's ability 
to live as they want. It will be used to measure quality of life (specific aim 3). 
Administration takes approximately 5 minutes after going through instructions, and can 
be interviewer or self-administered. Test-retest Reliability: total scale score r=0.93, 
physical r=0.89, emotional r=0.88. Internal Consistency: Total scale alpha 0.94, physical 

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0.94, emotional 0.90. Construct validity correlates with several other measures 
depending on extent of conceptual overlap.49  
7. Demographic, and comorbidity status will be collected using a standard 
questionnaire, the Charlson comorbidity index and chart review. Demographics 
collected via patient report, will be used to characterize the participant sample and 
obtain potential confounding variables such as age, sex, race/ethnicity, marital status, 
education completed, employment status, NYHA classification, and income. The clinic 
record will also be used to evaluate additional hospital stays (specific aim 4), and 
medications. The Charlson Comorbidity Index is a method of evaluating the effects of 
comorbidities in patients based on the International Classification of Diseases diagnosis 
codes found in billing data. The comorbidity has an associated weight, based on the 
adjusted risk of mortality or resource use, and the sum of all the weights results in a 
single comorbidity score for a patient. The higher the score, the more likely the 
predicted outcome will result in mortality or higher resource use.50  
8.The PROMIS Fatigue Scale assess a range of self-reported symptoms, from mild 
feelings of tiredness to an overwhelming, debilitating, and sustained sense of 
exhaustion. Fatigue is measured by frequency, duration, and intensity as well as the 
impact of fatigue on physical, mental, and social activities.51 The fatigue short form-8 is 
universal rather than disease-specific and assess fatigue over the past seven days. 
Each question usually has five response options ranging in value from one to five. With 
1= not at all, to 5=very much). To find the total raw score for a short form with all 
questions answered, sum the values of the response to each question. For example, 
the lowest possible raw score is 8; the highest possible raw score is 40. A higher 
PROMIS T-score represents more of the concept being measured. For negatively-
worded concepts like fatigue, a T-score of 60 is one SD worse than average. By 
comparison, a fatigue T-score of 40 is one SD better than average Patient-Reported 
Outcomes Measurement Information System (PROMIS) 7-day recall Fatigue Item Bank 
(www.assessmentcenter.net/). Validity was determined by multidisciplinary panel made 
of nurses, physicians, pharmacists and psychologists. 51-54 Reliability was found to be 
0.95 correlation with the FACIT-Fatigue scale.53 Support for using PROMIS fatigue in 
heart failure patients was found in one study, although the reliability scores were not 
printed.55  
9. Self-Efficacy for Exercise Scale is used to evaluate how strongly patients feel they 
can exercise in the face of common barriers. There are 9 items with 10 choices ranging 
from 0 meaning no confidence to 10 meaning very confident they could/would exercise 
despite the barrier. Reliability was demonstrated with a alpha coefficient of 0.93 and 
validity, by factor loadings of all 9 items greater than 0.50 and path coefficients greater 
than 0.70.56,57 This scale has been validated in a group healthy minority older adults and 
in a group of older adults ~85+ living in a retirement community (Caucasian, female and 
unmarried).56,57  
10. Outcome Expectations for Exercise Scale-2 is used to measure positive and 
negative expectations for engaging in exercise. There are 13 items with 5 choices on a 
scale range from 1 strongly agree, 2 agree, 3 neither agree or disagree, 4 disagree, 5 
strongly disagree. There are 2 subscales, one for the positive (9 items) or benefits 

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expected by engaging in exercise and the other on possible negative (4 items) 
outcomes from exercise. The each sub scale is then summed and divided by the 
number of items giving you an average score for positive and negative expectations 
score.58 Validity was demonstrated by factor and Rasch anylasis with a caveat of the 
negative subscales loaded on 2+ concepts suggesting some overlap.58 Internal 
consistency of both subscales was 0.93 for positive and 0.80 for the negative.58 
Reliability score was 0.98 and 0.91, respectively.58 
11. Repeated Sit to Stand Test is an objective physical test in which the person is asked 
to rise from a seated position 5 times as quickly as possible. This measures leg strength 
as well as balance and mobility.59,60 A systematic review was completed and found this 
test is good to high test-retest reliability using interclass correlations of 0.76-0.99 across 
studies, in most populations and settings.59,61,62 Excellent interrater reliability was 
demonstrated with interclass correlation of 0.99 across multiple clinicians in multiple 
health care settings.60-62 Poor performance on this test is associated with disability.63  
12. Timed up and Go Test (TUG) is an objective measure of physical functional status is 
a simple technique for evaluating competence in basic activities. The test measures in 
seconds how long it takes for someone to, stand up from a chair, walk forward 10 feet, 
turn around, walk back to the chair, and sit down.64 Reliability was been demonstrated 
by test-retest interclass correlations of 0.978-0.99 across studies done within 7 days.65 
Construct validity is acceptable with the measure demonstrating a specificity ranging 
from 87-97% and sensitivity from 83-87% for predicting older adults likely to fall.66,67  
With 12.3 seconds as the cut off score for predicting falls in the ensuring 6 month time 
frame with no ceiling effect demonstrated.66 TUG scores changed following a 
quadriceps and hamstrings strengthening program for patients with rheumatoid arthritis 
compared with subjects who received no strengthening. A reduction in time greater than 
or equal to 1.4 seconds is a major change and 0.2 is an unimportant change.68 
13. The Brief Pain Inventory Short Form (BPI-SF) is used to assess pain intensity and 
interference along with currently used pain management therapies.  The BPI-SF 
assesses:  intensity of pain through four items rated from 0 (no pain) to 10 (worst pain 
imaginable) that are averaged into one intensity score, current treatments being used 
(one item, open ended question), perceived pain relief (one item rated on a 0 to 100% 
scale), and extent that pain interferes with daily living through seven items rated from 0 
(no interference) to 10 (completely interferes) that are averaged into one interference 
score.69,70 The interference questions assess two types of interference with daily 
activities: affective social functioning (e.g., interaction with others) and physical 
functioning (i.e., ability to carry out daily activities).69,70  
The 15-item BPI-SF was developed for cancer pain patients, but has shown consistent 
validity and reliability for many conditions.71  Reliability in arthritis and low back pain 
patients is .82 for severity scale and .95 for the interference scale.72  Reliability in 
osteoarthritis patients for both severity and interference scales is 0.80 or greater.69 The 
BPI-SF is recommended for chronic pain clinical trials by IMMPACT.73 
14. The Patient Health Questionnaire (PHQ-8) was used to measure depression. The 
PHQ-9 is based on the Diagnostic and Statistical Manual of Mental Disorders for clinical 

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depression diagnostic criteria.74 Participants were asked to rate each of the 8 items by 
how often they had been bothered by the item over the past two weeks. The items are 
on a scale of 0= not at all, 1=several days, 2=more than half the days, 3=nearly every 
day. Time for participants to self-administer the instrument is less than 5 minutes 
(Kroenke, 2001).74 A total score of ≥10 has been shown to have a sensitivity and 
specificity of 88% in diagnosis of major depression and we used this cut off in this 
analysis.74 Due to the false positive reports on the last question of the PhQ-9, the PHQ-
8 has been recommended as the validity and reliability remain the same as the PhQ-9 
with correlation of 0.997, sensitivity of 50%, and specificity of 90%.75 
Table of variables and when they are obtained 
Variable 
When Collected 
Demographics, clinical data, Charlson 
Once Pre 
DXA (muscle mass) 
Pre, post, 6 months 
Dynamometer-Strength and torque 
(muscle) 
Pre, post, 6 months 
6-MWT (exercise capacity) 
Pre, post, 6 months 
ActivPal (time spent active) 
Pre, post, 6 months 
MSAS-HF (HF symptoms) 
Pre, post, 6 months  
MLHFQ (HF quality of life) 
Pre, post, 6 months 
Telephone interviews 
Weekly during intervention phase 
Promis Fatigue 
Pre, post, 6 months 
Self-Efficacy for Exercise Scale 
Pre, post, 6 months 
Outcome expectations for Exercise Scale 
Pre, post, 6 months 
Repeated Sit to Stand 
Pre, post, 6 months 
Timed up and go 
Pre, post, 6 months 
Self-Care of Heart Failure Index 
Pre, post, 6 months 
Brief Pain Inventory 
Pre, post, 6 months 
PHQ-8 
Pre, post, 6 months 
Compliance Data from EMPI machine 
Once post 
 
Section 6:   Reporting of Adverse Events or Unanticipated Problems involving 
Risk to participants or others 
 
The following standard definitions will be used for this study: 
 
Adverse Event (AE) 
 
Any untoward or unfavorable medical occurrence in a human study participant, 
including any abnormal sign (e.g. abnormal physical exam or laboratory finding), 
symptom, or disease, temporally associated with the participants’ involvement in the 
research, whether or not considered related to participation in the research. 
 
Serious Adverse Event (SAE) 
 

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Any AE where the participant is at immediate risk of death from the event as it occurred, 
or results in inpatient hospitalization, prolongation of existing hospitalization, persistent 
or significant disability/incapacity, or death.  
 
Unanticipated Problem  
 
As Defined by DHHS 45 CFR part 46, any incident, experience, or outcome that meets 
all of the following criteria:  
• 1) is unexpected, in terms of nature, severity, or frequency, given (a) the 
research procedures that are described in the protocol-related documents, such 
as the IRB-approved research protocol and informed consent document; and (b) 
the characteristics of the study population;  
• 2) is related or possibly related to participation in the research (in this guidance 
document, possibly related means there is a reasonable possibility that the 
incident, experience, or outcome may have been caused by the procedures 
involved in the research); and  
• 3) suggests that the research places participants or others at a greater risk of 
harm (including physical, psychological, economic, or social harm) than was 
previously known or recognized. 
  
AEs will be graded according to the following scale: 
 
• Mild: An experience that is transient, and requires no special treatment or 
intervention. The experience does not generally interfere with usual daily 
activities. This includes transient laboratory test alterations. 
• Moderate: An experience that is alleviated with simple therapeutic treatments. 
The experience impacts usual daily activities. Includes laboratory test alterations 
indicating injury, but without long-term risk. 
• Severe: An experience that requires therapeutic intervention. The experience 
interrupts usual daily activities. If hospitalization (or prolongation of 
hospitalization) is required for treatment it becomes an SAE. 
 
Attribution of AEs will be categorized as: 
 
• Not related: The AE is clearly not related to the study procedures (i.e., another 
cause of the event is most plausible and/or a clinically plausible temporal 
sequence is inconsistent with the onset of the event).  
• Possibly related: An event that follows a reasonable temporal sequence from the 
initiation of study procedures, but that could readily have been produced by a 
number of other factors. 
• Likely Related: The AE is clearly related to the study procedures.  
 
Reporting of AEs, and unanticipated problems will follow the guidelines of the IU 
Standard Operating Procedure for Reporting Unanticipated Problems and 

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Noncompliance. Specifically, the following events will be reported promptly (i.e., within 
five business days) to the IRB: 
 
• AEs that are assessed by the PI or coinvestigators as (1) unexpected, (2) related 
or possibly related to participation, AND (3) suggests that the research places 
subject(s) or others at greater risk of harm than was previously known; 
• Major protocol deviations that may, in the opinion of the PI, (1) impact subject 
safety, (2) affect the integrity of the data, OR (3) affect study participant' 
willingness to participate in the study; 
• Noncompliance, which includes any action or activity associated with the conduct 
or oversight of the research that fails to comply with federal or state regulations, 
institutional policies governing human study participant research, or the 
requirements or determinations of the IRB. 
 
Unanticipated problems that do not meet the criteria for prompt reporting will be 
reported at time of protocol renewal to ensure the IRB has a full understanding of the 
conduct of the research. 
 
Data Safety Monitoring (DSM) Plan 
 
Although the intervention is low risk, we will evaluate all expected and unexpected 
events to ensure the safety of participants and integrity of the study protocols and data. 
Research team members (RA, PI) will meet weekly and review all aspects of the study, 
including preparation of materials and equipment, recruitment, accrual, drop out, data 
collection, data entry, and protocol adherence for the first 3 months then at least 
monthly after that. Questions and concerns will be addressed at that time. 
 
 The PI, Dr. Haedtke, will be responsible for overall monitoring of the study. The PI and 
Co-investigators will attend monthly meetings. Dr. Haedtke will be responsible for 
submitting necessary reports to the members.  
• Susan J. Pressler, PhD, RN, FAAN, FAHA, Co-investigator, Professor and Sally 
Reahard Chair Director, Center for Enhancing Quality of Life in Chronic Illness 
(CEQL), Indiana University School of Nursing; participate in meetings and be 
particularly involved with advising on recruitment, accrual, retention, reports of 
expected and unexpected adverse events, and data quality.  
• 2) Peter Pang, MD, MS, FACEP, FACC, Co-investigator, Director of Clinical 
Research, Chief Science Office, CORE, Indianapolis EMS, Indian University 
School of Medicine; participate in meetings and be particularly involved with 
recruitment, accrual, retention, and reports of expected and unexpected adverse 
events. 
• 3) Janet Carpenter, PhD, RN, FAAN, Independent reviewer, School of Nursing 
Associate Dean for Research, Distinguished Professor, will perform an 
independent review of the expected/unexpected adverse event data to assure 
non-bias by the PI on a monthly basis.   
 

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Minimizing research-associated risk.  
• Protocols for teaching patients how to safely apply the electrodes and monitor 
their skin will be verbalized with the patient. Following the teaching the patient 
will teach back what was learned. If not complete or correct, additional 
information will be given with the patient again verbalizing all key points. If the 
patient is unable to complete this task, they will be excluded from the study. We 
will provide written handouts with directions and pictures of proper placement of 
electrodes. The RA will call the patients weekly while they are using the EMPI 
machine to determine safety and potential skin irritation or muscle soreness.  
• For patients who have scores on the PHQ-8 suggestive of high depressive 
symptoms (scores > 10) Dr. Haedtke will follow-up with patients’ individual 
physicians after alerting the patient.  
• Adherence to the safety protocols will be reviewed at weekly team meetings and 
at monthly Co-Investigator meetings. In addition, Dr. Haedtke will provide 
continuous, close monitoring of protocol adherence and referral of patients if 
needed. 
 
Dr. Haedtke will be responsible for reporting unexpected adverse events and 
unanticipated problems as required by the IU IRB. The IU IRB will be notified in writing 
of adverse events within 5 business days of identification of events. During each visit, 
the PI or RA will question the patient about adverse events using an open question, 
taking care not to influence the patient’s answers, e.g. “Have you had any unusual 
symptoms or medical problems since the last visit?” It is expected that many HF 
patients will have events that are commonplace due to their HF and associated 
comorbidities. 
Determining if an Adverse Event needs to be reported to the IRB 
1. Is the occurrence unexpected during the course of the study? 
a. We expect skin irritation and minor muscle soreness, complications that 
occur as a result of protocol-mandated use of the EMPI machine, these 
events will not be reported.   
2. Is the occurrence related (or possibly related) to the study? 
a. Not including the expected events, if yes and unexpected, then the event 
will be reported to the IRB. 
3. Does the event put participants at greater risk of harm? 
a. Is there something we could change in the protocol to decrease the 
likelihood of another event, if yes, then modification will be submitted. 
b. Was this participant specific and unlikely to happen to other participants?  
If yes, no changes will be made. 
 
Each reported adverse event will be described by its duration (i.e., start and end dates), 
and suspected relationship to study protocol. These relationships are categorized as 
likely, possible, and not related. To ensure consistency, PI will apply the following 
general guideline:  

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Version Date: February 5, 2019 
• Yes - There is a plausible relationship between the onset of the adverse event 
and administration of the study protocol. 
o The adverse event cannot be readily explained by the subject’s clinical 
state, inter-current illness, or concomitant therapies; event abates or 
resolves upon discontinuation of use of the EMPI machine. 
o No - Evidence exists that the adverse event has an etiology other than the 
study protocol (e.g., preexisting medical condition, underlying disease, 
inter-current illness, or concomitant medication); and/or the adverse event 
has no plausible relationship to the study.  
 
The RA will notify the PI of any event if found when PI was not present and give all 
information collected so far. The PI will review the medical chart to assist in determining 
potential causes if necessary. Next, the PI will contact members of the clinical care 
team to clarify uncertainty related to inadequate documentation, if necessary. Third, if 
the PI is unable to decide for certain if an adverse event is study related, he or she will 
have the option of sending a personal health identifier-stripped, written narrative of the 
event to the other co-PIs who will assist as to whether the event constituted an adverse 
event. All adverse events will be followed through resolution, stabilization, or until the 
subject is lost-to-follow-up. 
 
Dr. Haedtke will conduct a literature search and review scientific reports monthly to 
determine if new studies/protocols/warnings have been published about NMES/TENS 
interventions in HF or other conditions. If new publications are found, they will be 
reviewed by the PI and if deemed important, Co-Investigators for impact on the safety of 
participants or ethics of the study. 
 
Section 7:   Study Withdrawal/Discontinuation 
A participant may withdrawal from the study at any time verbally or by providing this 
request in writing as described in the informed consent document.  As outlined in the 
consent document, if the participant/patient wishes to withdraw consent, the PI will not 
take back any research/analyses already completed. 
 
Section 8:   Statistical considerations 
 
Data Management and Analysis  
 
Data collection will occur at the CTSI in IU Health main campus. All data are 
entered online using the REDcap system. REDcap is a secure web based application 
for building and managing databases, sponsored by a consortium of 118 research 
institutions. It offers a streamlined process for building a database, interface for data 
collection and validation, and automated export procedures for downloading to 
statistical packages. All REDcap data are stored on a secure web server located behind 
a firewall on the CCTS network. The ActivPal data will be downloaded from the device 
directly to a Box Health account with Study ID used as the identifier. 
The risk of breach of confidentiality of patient data will be minimized by ensuring 
all involved personnel have a full understanding of the Health Insurance Portability and 

Page 18 of 42 
 
Version Date: February 5, 2019 
Accountability Act (HIPAA) rules and the protection of privacy guidelines for conducting 
medical record reviews through the completion of all IRB-mandated HIPAA training and 
education. Data gathering instruments and procedures are carefully designed to limit 
the access of personal information. Password protected laptop dedicated for this study 
only will be used to enter data. Each participant will be assigned a unique identification 
number and all of their records marked only with this number. All hard copies of data 
(consents) will be kept in a locked file in the PI’s office separate from the files containing 
the identification key. All digital data reside on computers with encryption software that 
are password protected and that are kept in locked offices in a locked office suite 
available only to members of the research team. 
 
Missing Data  
 
The research associate will review all data collected for completeness and 
readability, correcting any errors prior to data analysis. We will collect “reason for drop 
out” if a participant stops the study. We will continue to try to schedule subsequent data 
collection interviews even if the participant is not able to complete a previous one. 
During each data collection session, team members will work with participants to 
encourage response to all items and will review data to ensure all data points are 
completed unless the participant prefers not to answer. Nonetheless, missing data will 
occur and this will be acknowledged in the analysis.76 We will conduct initial analyses 
using the maximum likelihood approach, as it emphasizes the use of all available data. 
The use of random effects modeling techniques, in particular repeated measures mixed 
modeling, allows for missing data by adjusting the estimation process to account for 
bias resulting from data missing at random. Baseline data from those with and without 
missing data will be compared to determine whether there are systematic differences, 
using demographic and personal variables. If the data are not amenable to the 
maximum likelihood method random effects analysis, multiple imputation will be used as 
an alternative procedure for handling missing data. Multiple imputation produces results 
similar to maximum likelihood when used under identical conditions. We will use 
multiple imputation in the sensitivity analyses; this will allow for the comparison of study 
results under a variety of assumptions to assess the robustness of the findings. 
 
Statistical Analysis 
 
Data analysis will be done using SPSS, v. 22; an alpha level of .05 will be used 
for all tests except where noted. Study measures will be examined using univariate 
statistics, including means, standard deviations and frequency distributions, and 
graphical techniques, such as box plots and histograms.  Distributions for continuous 
outcome measures will also be examined for violations of normality using normal 
probability plots. If there is evidence of lack of normality for a particular outcome, 
transformations (e.g., logarithmic) will be used so that the distribution of the transformed 
variable more closely approximates normality. The analysis strategy to be used to test 
all aims is repeated measures analysis of variance (ANOVA). Each ANOVA model will 
include the main effects of Time (baseline, 6 weeks, 6 months’ post intervention period) 
and Group (intervention and sham intervention), as well as the Time by Group 

Page 19 of 42 
 
Version Date: February 5, 2019 
interaction. Post-hoc pairwise comparisons of means will be done using Fisher least 
significant difference procedure. The repeated measures models will be estimated using 
the MIXED procedure in SAS. This analysis will: test the effect of NMES on muscle 
mass and strength in those with HF (Aim 1); evaluate the effect of NMES on 
exercise capacity and activity (Aim 2); and assess the effect of NMES on HF 
symptoms and quality of life (QOL); and finally, evaluate the effect of NMES on 
enrollment and utilization of a formalized exercise program (aim 4). There will be a 
separate model for each outcome variable, and the significance of the main and 
interaction effects will indicate the effect of the intervention over time.  
 
Power Considerations 
 
With at least 27 subjects per group (treatment and sham) completing the study 
and an alpha level of .05, the ANOVA F test will have approximately 97% power to 
detect a significant main or interaction effect, assuming a large effect size, and a 
modest degree of correlation among observations from the same individual. A large 
effect size in this context is one such that the ratio of the standard deviation of the 
means to the standard deviation of the observations within the populations is at least 
0.4.77 In addition, the ANOVA F tests will have at least 69% power to detect main effects 
and 95% power to detect an interaction effect, with alpha set at .05 and at least a 
medium effect size (i.e., ratio of standard deviation of means to standard deviation of 
observations within populations is at least 0.25). Given that we expect a large effect 
between the groups for many outcomes, in addition to the estimated power of at least 
95% for the detection of a Group by Time effect in the presence of a medium to large 
effect, the sample size chosen for this exploratory study will provide sufficient power to 
detect this significant group differences over time with a high probability; in addition, this 
study will allow us to more precisely measure expected power in order to plan future 
studies.  
 
Section 9:   Privacy and Confidentiality Issues 
Patients’ confidentiality will be preserved by coding each data sheet with a unique 
subject number, and storing the code number key in a locked file cabinet in a locked 
research office located in the School of Nursing.  Protection against breach of 
confidentiality is provided by training all individuals involved in the research process 
about the necessity for complete confidentiality, housing all data collected in locked file 
cabinets in an access-restricted area, and by use of password protected computers and 
secure servers. Most data are collected using the REDcap system, and any additional 
files with be stored in Box Health on IU Servers. Although there can be no absolute 
guarantee of confidentiality, every practical precaution will be taken. 
 
Section 10: Follow-up and Record Retention 
Study recruitment will be ongoing.  The duration of the entire study is expected to 
be 18 months, while each participants expected duration is 6 months. The de-identified 
data will be retained on computer files indefinitely. Hard copy study documents will be 
kept in a locked, file cabinet in a locked room. Electronic study information will be stored 

Page 20 of 42 
 
Version Date: February 5, 2019 
on a specified, password-protected network that is backed up daily (BOX Health). Only 
the study team and the relevant personnel will have access.  
 
 

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Cella D, Riley W, Stone A, et al. The Patient-Reported Outcomes Measurement 
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2010;63(11):1179-1194. 
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Junghaenel DU, Christodoulou C, Lai JS, Stone AA. Demographic correlates of fatigue 
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55. 
Flynn KE, Dew MA, Lin L, et al. Reliability and construct validity of PROMIS(R) 
measures for patients with heart failure who undergo heart transplant. Qual Life Res. 
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56. 
Resnick B. Testing a model of exercise behavior in older adults. Res Nurs Health. 
2001;24(2):83-92. 
57. 
Resnick B, Jenkins LS. Testing the reliability and validity of the Self-Efficacy for 
Exercise scale. Nurs Res. 2000;49(3):154-159. 
58. 
Resnick B. Reliability and validity of the Outcome Expectations for Exercise Scale-2. J 
Aging Phys Act. 2005;13(4):382-394. 
59. 
Lord SR, Murray SM, Chapman K, Munro B, Tiedemann A. Sit-to-stand performance 
depends on sensation, speed, balance, and psychological status in addition to strength in 
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Bohannon RW, Bubela DJ, Magasi SR, Wang Y-C, Gershon RC. Sit-to-stand test: 
Performance and determinants across the age-span. Isokinetics and exercise science. 
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Bohannon RW. Test-retest reliability of the five-repetition sit-to-stand test: a systematic 
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Wallmann HW, Evans NS, Day C, Neelly KR. Interrater Reliability of the Five-Times-
Sit-to-Stand Test. Home Health Care Management & Practice. 2013;25(1):13-17. 
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Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery 
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Noren AM, Bogren U, Bolin J, Stenstrom C. Balance assessment in patients with 
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66. 
Wrisley DM, Kumar NA. Functional gait assessment: concurrent, discriminative, and 
predictive validity in community-dwelling older adults. Phys Ther. 2010;90(5):761-773. 
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Shumway-Cook A, Brauer S, Woollacott M. Predicting the probability for falls in 
community-dwelling older adults using the Timed Up & Go Test. Phys Ther. 
2000;80(9):896-903. 
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Wright AA, Cook CE, Baxter GD, Dockerty JD, Abbott JH. A comparison of 3 
methodological approaches to defining major clinically important improvement of 4 
performance measures in patients with hip osteoarthritis. J Orthop Sports Phys Ther. 
2011;41(5):319-327. 
69. 
Kapstad H, Rokne B, Stavem K. Psychometric properties of the Brief Pain Inventory 
among patients with osteoarthritis undergoing total hip replacement surgery. 
HealthQualLifeOutcomes. 2010;8:148. 
70. 
Mendoza T, Mayne T, Rublee D, Cleeland C. Reliability and validity of a modified Brief 
Pain Inventory short form in patients with osteoarthritis. EurJPain. 2006;10(4):353-361. 
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Kumar SP. Utilization of brief pain inventory as an assessment tool for pain in patients 
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Keller S, Bann CM, Dodd SL, Schein J, Mendoza TR, Cleeland CS. Validity of the brief 
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Furlanetto LM, Mendlowicz MV, Romildo Bueno J. The validity of the Beck Depression 
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Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity 
measure. J Gen Intern Med. 2001;16(9):606-613. 
75. 
Razykov I, Ziegelstein RC, Whooley MA, Thombs BD. The PHQ-9 versus the PHQ-8--is 
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Version Date: February 5, 2019 
Section 12 Appendix 
 
Section 12A SOP for ActivPal 
 
Standard Operating Procedure for Programming ActivPal 
Step 1: Open the ActiPal spreadsheet and find the corresponding serial number  
Step 2: Open Pal app, make sure the docking station is plugged into the USB port on 
the computer, and place the monitor in the end spot that says “PC interface”. 
Step 3: put in Study ID BISTROxx, for 14 days 
Step 4: Click on Set up Recording, this takes a few minutes 
 
Standard Operating Procedure for Downloading data from ActivPal 
 
Step 1: participant returns ActivPal either in person (baseline visit) or receive unit in 
mailer, remove any tape or waterproofing that may still be applied.  
 
Step 2: Wipe down the outside of the monitor with cleanings wipes and allow to dry. 
 
Step 3: open PALstudio app, make sure the docking station is plugged into the USB 
port, and place the monitor in the end spot that says “PC interface”. 
 
Step 4: click on “transfer”, the computer then looks to find the ActivPal. It will show you 
the serial number of the ActiPal data that is getting downloaded. Double check to make 
sure the one you mean to be downloading is in fact the one getting downloaded. This 
takes a few minutes so work on something else while you wait. Once the files are then 
downloaded and then “verified” by the program. 
 
Step 5: Open BOX Health, verify the file is there and open file to be sure data is in the 
file.   
Step 6: Click on Analyze in the PAL studio app, click on all 4 boxes to get all data. 
Step 7: Click on Reports and chose the “ASOD”- The standard algorithm with inverted 
wear correction” option then click Generate reports.   
Step 8: Look in BOX Health and verify the file is there and open all files to be sure there 
is data in the file. 
 
Instructions for Participants 
 
 

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Version Date: February 5, 2019 
 
 
BISTRO Patient: 
ActivPAL Instructions 
 
 
 
 
 
 
 
Table of Contents 
 
Information about the study  
 
        
2 
 
How to Apply the ActivPAL  
 
 
 
3 
 
How to Remove the ActivPAL   
 
      5 
 
 

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Version Date: February 5, 2019 
The ActivPAL is designed to monitor activity 
levels and identify periods of sitting/lying, standing, 
and walking. We have incorporated the ActivPAL 
into our study to determine if the intervention will 
affect your activity level and exercising habits. We 
ask that you wear it 3 times during the study for one 
week each time. First when you begin the study, 
second after participating in the intervention, and 
third at the 3-month mark following completion of 
cardiac rehabilitation. 
During each use, we request that you wear the 
ActivPAL on your thigh, 24 hours a day for 7 days. 
We will supply a waterproof covering for the 
ActivPAL, which will cover the ActivPAL at all times, 
even when you shower. If needed, extra materials to 
reapply the ActivPAL will be supplied at no cost to 
you.  
Once the ActivPal is programed for your use, the 
bottom light on the ActivPAL will flash green. If the 
light stops flashing at any time during the week you 
have it, please contact the research assistant listed 
in the study paperwork given to you when you joined 
the study.  Also, if skin irritation occurs at any time 
while you are wearing it, please contact the research 
assistant.  
 

Page 29 of 42 
 
Version Date: February 5, 2019 
 
 
How to Apply the ActivPAL:  
1. Carefully wash and dry the area of skin where 
the ActivPAL will applied.  
2. Obtain the ActivPAL. Orient it so that the body 
on the ActivPAL is standing up. (See picture 
above.) You will notice the rounded side is up, 
and the square side is down. Lights face away 
from your skin. 
3. Cover the ActivPAL with the waterproof covering 
and roll the end to the side away from you.   
4. Sit down on a chair when attaching the monitor 
so that it will be easier to find the best place for 
attachment. You want to place it on the top 1/3rd 
of the length between your groin and your knee 
in the midline width of your thigh as shown in the 
picture below. 
 

Page 30 of 42 
 
Version Date: February 5, 2019 
 
 
 
5. Apply the Skin-PREP wipe to the area of skin 
where the ActivPAL will be. This will protect your 
skin from the adhesives in the tape and allow 
the tape to perform better.  
6. Place the covered ActivPAL in the correct 
orientation on the upper thigh. See picture 
above. The ActivPAL should be worn on your 
non-dominant side.   
7. Use a large piece of Tegaderm tape to 
completely cover the ActivPAL. Ensure that this 
adheres directly to the skin. 
 
 
 
 
 

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Version Date: February 5, 2019 
Removing the ActivPAL: 
1. Carefully peel the Tegaderm away from the skin 
by lifting up a single corner of the material and 
gently pulling away from your skin, but level to 
the bandage.  
2. Remove the ActivPAL, encased in its waterproof 
covering, from the skin.  
3. Carefully wash and dry the skin where the 
ActivPAL was applied with mild soap. If skin 
irritation has occurred, please contact research 
assistant.  
4. Place the ActivPAL in the bubble mailer we gave 
to you and place it in any US mail box for return 
to us.  
5. ActivPAL needs to be received by us before we 
can issue your study participation check.  
 
 
 
If you have any questions about the 
ActivPAL or the study at any time 
please call the research assistant. 
  
Thank you for participating in our 
study! 
 
 

Page 32 of 42 
 
Version Date: February 5, 2019 
Section 12B SOP for EMPI 
 
EMPI Standard Operating Procedure for setting up TENS 
Machine Set up: do this before you see the participant. Please note, you may not need 
to make adjustments to the machine due to previous programming, so if the correct 
option is chosen move on to the next item. 
1. Turn on machine 
2. Press “Home” button 
3. Press the TENS button (bottom Left) 
4. Press the lower left bottom button until “Custom”, then press OK 
5. Change “Time” to 15 MIN, Use the right buttons to raise or lower to 15 MIN, then 
press bottom left button to progress to “Rate”. 
6. Leave “Rate” at 100Hz , then press the bottom left button to progress “Cycle” 
7. Set “Cycle” to 15S, then press the bottom left button to progress to “Span” 
8. Set “Span” to 50%, then press the bottom left button to progress to “Mode”  
9. Set “Mode” at MOD, then Press OK 
10. Now the machine is set up for participant to test the comfort level. 
 
Once the Data collector has told you the participant is ready for the intervention explain 
the machine to them by giving them the EMPI handout and going through each step 
with the participant following the directions and you clarifying when necessary.  Make 
sure a garbage can and table with a bowl for warm water and wash cloth and towel is 
within reach, (show them how to use the trimmer if necessary), give them the EMPI 
handout, go through each step of the process with them.  Once the patches are placed 
and the participant is ready to turn on the machine, show them the picture on page 3 
and explain the need to use the on/off button and the increase/decrease intensity 
buttons. Have them start increasing the intensity on either channel slowly at first and 
closely monitor their reactions to it.  For this intervention we are just looking for a 
general “feeling it”. They should not increase the intensity to the point where a muscle 
contraction happens! 
Once you are confident the participant settings are comfortable for the patient and only 
intensity needs to be adjusted, LOCK the device so the participant cannot change the 
settings themselves.  
1. Press the Home button, config (right lower), locks (right lower)  
2. Notice the NMES L.  Muscles and press the right top button, which locks that 
option 
3. Press the left lower button to bring up S. Muscles and press the right top button 
twice to get a circle with a line through it. Now that option will no longer show for 
participants. Repeat for TENS and Edema then press home and note only L. 
Muscles is an option besides config. 
 
 

Page 33 of 42 
 
Version Date: February 5, 2019 
EMPI Standard Operating Procedure for setting up NMES 
 
Machine Set up: do this before you see the participant. Please note, you may not need 
to make adjustments to the machine due to previous programming, so if the correct 
option is chosen move on to the next item.  
1. 
Turn on machine 
2. 
Press “Home” button 
3. 
Press the NMES button (top left) 
4. 
Large muscle (top left) 
5. 
Press the Custom button (bottom right) 
6. 
Change time to 15 minutes, then press bottom left button to progress to “off time” 
7. 
Change Off time to 15 Seconds, then press bottom left button to progress to “rate 
8. 
Increase “Rate” to 50Hz, then press the bottom left button to progress to “Width” 
9. 
Leave “Width” at 300 to start. Press bottom left button to progress “waveform”. 
10. 
Leave “waveform” at SYM/ASY 
11. 
Change Cycling “LAG” for both legs at the same time.  
12. 
Leave “Lag” at 0S 
13. 
Leave “CH1 Ramp +” at 2S 
14. 
Increase “ON TIME 1” to 11S 
15. 
Leave “CH1 RAMP –“at 2S 
16. 
Leave “CH2 Ramp +” at 2S 
17. 
Increase “ON TIME 2” to 11S 
18. 
Leave “CH1 RAMP –“at 2S, then press OK  
19. 
Now the machine is set up for participant to test the comfort level. 
 
Once the Data collector has told you the participant is ready for the intervention explain 
the machine to them by giving them the EMPI handout and going through each step 
with the participant following the directions and you clarifying when necessary.  Make 
sure a garbage can and table with a bowl for warm water and wash cloth and towel is 
within reach, (show them how to use the trimmer if necessary), give them the EMPI 
handout, go through each step of the process with them.  Once the patches are placed 
and the participant is ready to turn on the machine, show them the picture on page 3 
and explain the need to use the on/off button and the increase/decrease intensity 
buttons. Have them start increasing the intensity on either channel slowly at first and 
closely monitor their reactions to it.  The intensity needs to be strong enough to cause 
the muscle to contract. Demonstrate how actively using the muscle during the 
contraction lessens any discomfort. 
 
20. 
If the participant reports the feeling is uncomfortable or “bity” adjust the “Rate” to 
make the sensation more “smooth”. Decrease the Rate by 5 to 45 then have the 
participant try again. (Can adjust in increments of ±1 to get the “best” feel for 
participants. Be sure to record the final setting you programed into the machine in both 
Redcap and the participant call sheet.) To make adjustments to Rate, (you not the 

Page 34 of 42 
 
Version Date: February 5, 2019 
participant!) press the home button, NMES, Custom, the press the left lower button until 
you see “Rate”, then use the right lower button to make the adjustment, then press OK 
and have the participant try again.   
 
21. 
If the participant reports the feeling is still uncomfortable or “bity” lower the 
WIDTH by 8 and see if that makes it better. (Can adjust in increments of ±4 to get the 
“best” feel for participants. Be sure to record the final setting you programed into the 
machine in Redcap and on your participant call sheet.) To make adjustments to Width, 
You (not the participant!) need to press the home button, NMES, Custom, the press the 
left lower button until you see “Width”, then use the right lower button to make the 
adjustment, then press OK and have the participant try again.  
 
Once you are confident the participant settings are comfortable for the patient and only 
intensity needs to be adjusted, LOCK the devise so the participant cannot change the 
settings themselves.  
1. 
Press the Home button, config (right lower), locks (right lower)  
2. 
Notice the NMES L.  Muscles and press the right top button, which locks that 
option 
3. 
Press the left lower button to bring up S. Muscles and press the right top button 
twice to get a circle with a line through it. Now that option will no longer show for 
participants. Repeat for TENS and Edema then press home and note only L. Muscles is 
an option besides config. 
 
 
 

Page 35 of 42 
 
Version Date: February 5, 2019 
Standard operating procedure when EMPI units are returned 
 
Expect participants to bring the unit in the study canvas bag along with any unused 
sealed supplies.  
 
Step 1: log into RedCap, bring up the data entry for the EMPI machine, enter the study 
ID. 
Step 2: once you have the Canvas bag with EMPI unit, use the wipes designated for 
cleaning the machine to wipe down the outside of the machine and the lead 
wires and allow them to air dry.  
Step 3: turn on the machine, identify if NMES or TENS showing on the main menu and 
enter that data into RedCAp 
Step 4: press the home button, config button (right lower), data button (left upper). 
Step 5:  enter the number of sessions into RedCap, press the left down button  
Step 6:  enter the Total hours into RedCap, press the left down button 
Step 7:  enter the average time into RedCap, press the left down button 
Step 8:  enter the CH 1 intensity into RedCap, press the left down button 
Step 9:  enter the CH 2 intensity into RedCap, press the home button. Double check 
you have entered all data into RedCap. 
Step 10: press the home button, config, clear (right lower), data, and then home. The 
data has been erased from the machine and is ready for the next participants 
set up.   
 
 
 

Page 36 of 42 
 
Version Date: February 5, 2019 
 
 
BISTRO Patient Instructions: 
Empi Unit 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table of Contents 
 
 
 
 
Page number 
Skin Preparation  
 
 
 
 
         2 
Using Your Empi Unit  
 
 
 
 
3 
Caring for the Empi Unit  
 
 
           
6 
Troubleshooting for the Empi Unit  
     
 
6 
 
 
 
    
 
 
 
 
 
 

Page 37 of 42 
 
Version Date: February 5, 2019 
We have provided the following with your Empi unit for your use 
during the study: a canvas bag, patches, wires, skin preparation pads, 
notebook with pen, trimmer (optional for those with hairy thighs), and extra 
AA batteries. If you need additional supplies at any time, call the research 
assistant.  
Before beginning the treatment, you must protect your skin. 
Skin Preparation: 
1. Always check the skin carefully prior to beginning stimulation. The skin 
should not have any cuts, open sores, rashes, or inflammation.  
What to do if a skin problem occurs: Carefully wash and dry the area 
with mild soap (unscented), rinse, and use a soft towel to dry the area. Call 
the research assistant and inform them of your skin problem. You will need 
to pause treatment until your skin heals. 
2. If your skin is healthy, wash the skin where the patches will be placed 
(see picture below). Do not apply any lotions, gels, or perfumes to the 
skin. Gently dry the skin with a soft towel.  
3. If there is any hair in the area where the patches will be placed, remove 
the hair with a trimmer. Do Not use a razor as this will lead to skin 
irritation and minor cuts.  
4. After washing, drying, and the removal of hair, open the skin preparation 
pads (SKIN-PREP) found in the canvas bag and thoroughly wipe the 
area where the patches will be placed. Wait 30 seconds for the SKIN-
PREP to dry, then place the patches. 

Page 38 of 42 
 
Version Date: February 5, 2019 
 
Using Your Empi Unit  
1. Make sure that the skin where the patches will be placed has been 
washed, dried, and SKIN-PREP applied.  
2. Make sure that the unit is turned off. 
3. Open the sealed bag with the patches found in the canvas bag. Gently 
peal the patches off the plastic sheet and save the sheet to return the 
patches when your session is complete. The patches are reusable and 
should be changed every week. If the patches don’t want to stick they 
maybe dry. You can add 1 or 2 drops of water to the patch, if it still 
doesn’t stick, use a new set. 
4. Plug the wire connector from the patch to the wire on the machine. Note: 
The wire connectors may connect to either the red or black connectors. 
The black wire connected to the patch at the top of the thigh and the red 
connector the patch near the knee. If there is wire damage call research 
assistant for a new set. 
5. Place the patches in the correct locations as indicated in the diagram on 
page 2. Stick the center of the patch on the desired area of the skin, and 
then flatten the sides of the patches onto the skin.  

Page 39 of 42 
 
Version Date: February 5, 2019 
 
6. Remove the unit from the canvas bag and turn the unit on using the 
ON/OFF button in the middle of the bottom row on the unit, just below 
the screen. When you turn on the unit, the screen will present the 
Empi logo (See picture above). 
7. Next, the screen should display an “In-Progress” message indicating 
that the unit is ready for use.  
a. If the screen goes to a menu that displays options for you to 
select (i.e., NMES, TENS, EDMEA, CONFIG), call the research 
assistant as additional directions will be needed for you to safely 
use the machine.  
8. Once the “In-Progress” screen appears, you need to increase the 
level of intensity for treatment. Adjust the intensity to the level 
specified by the research assistant.  
a. To increase the intensity for Channel 1, press the top button on 
the left-hand side of the screen. To decrease the intensity for 
Channel 1, press the bottom button on the left-hand side of the 
screen.  
b. To increase the intensity for Channel 2, press the top button on 
the right-hand side of the screen. To decrease the intensity for 
Channel 2, press the bottom button on the right-hand side of the 
screen.  

Page 40 of 42 
 
Version Date: February 5, 2019 
c. Note: Once the intensity is set and left alone for 20 seconds, the 
unit will lock the buttons to prevent an unwanted change. In order 
to change the intensity after the unit is locked, press the decrease 
intensity button on the desired channel to unlock the unit so you 
can change the intensity.  
d. Unit will stop running after 15 minutes. You can now turn off the 
machine by pressing of on/off button for 2 sections and remove 
the patches. 
9. Removing the patches  
a. Turn off the unit before removing the patches. 
b. Carefully pull the patch off the skin starting at a corner. The wire 
connectors should not be used to help pull the patches off! 
Pressing on the skin with your other hand close to where you are 
removing the patch makes removal easier.  
c. Reapply the patches to the liner. Making sure the patch is flat on 
the liner.  
d. Separate the wire from the connector of each patch by gently 
unscrewing and lightly tugging where they join. Seal the bag with 
the patches to keep them from drying out. Return the machine and 
patches to the canvas bag for storage until your next use.   
10. Carefully wash and dry the skin where the patches were applied with 
mild soap, rinse, and wipe with a soft towel. Some redness is 
expected after immediate removal of patches. If the redness remains 
after an hour or is bothersome in any way, write down what you are 
seeing and feeling in the notebook included in the canvas bag and 
call the research assistant. (For details see Skin Prep section on 
page 2) 
 
 

Page 41 of 42 
 
Version Date: February 5, 2019 
Caring for the Empi Unit: 
Maintenance:  
• The unit is designed to function without regular maintenance. Call the 
research assistant if you have concerns.  
Cleaning: 
• If the unit becomes dirty, use a nonabrasive, damp cloth to wipe off 
the unit. Refrain from use any chemicals or cleaning solutions to 
clean the unit. Do not place the unit in any liquids.   
Storage: 
• Although the unit will be used regularly, avoid leaving the unit out 
following use. The wires are easily tangled, targets for pets, or a 
potential tripping hazard.  Use the canvas bag provided to store the 
unit at room temperature.  
Having problems with the Empi Unit? 
If the unit displays the low battery symbol or message or the unit will not 
turn on replace the batteries.  
How to replace the batteries:  
1. Turn off the device.  
2. Turn the unit over so the backside towards you. Remove the 
battery cover by placing your thumb on the notch and the bottom 
backside of the unit and pushing up while pulling out.  
3. Remove the old batteries. 
4. Place new batteries in the unit by matching the + and – ends of the 
battery with those on the unit. Only use the AA batteries provided 
by the study to replace the batteries in the unit. If you do not have 
any AA batteries left, call the research assistant.  
5. Replace the battery cover by inserting the small lip at the base of 
the cover. Then, insert the top of the cover and press until it clicks 
securely in place. Check the batteries in the unit and make sure 
that the + and – ends on the batteries match the + and – symbols 
on the unit. Check to ensure that there is nothing hindering the 
batteries from touching the respective + and – ends of the unit.  
If the unit powers on but the buttons are not functioning properly, check 
the following: 

Page 42 of 42 
 
Version Date: February 5, 2019 
a. 
Disconnect the wires from Channel 1 and Channel 2.   
b. 
Remove the batteries from the unit. And leave the batteries out 
for 10 seconds.  
c. 
Replace the batteries in the unit and try running the treatment 
again.  
If the unit powers on and the screen appears correct but you do not feel 
any stimulation, check the following: 
a. 
Check to make sure that the intensity is to the minimum level 
specified by study personnel.  
b. 
Check the lead wires and make sure that they are properly 
connected to both the patches and the unit in the proper 
locations (i.e., Channel 1 and Channel 2).  
c. 
Check the wires for any damage or disconnections to either the 
unit or the patches. If the wires are damaged on the machine 
call the research assistant for a new pair. If the connection on 
the patches is damaged, use a new pair.  
If the unit powers on and the screen displays an “OPEN” error message 
check the following: 
a. 
Turn off the machine and check to make sure that the patches 
and wires are connected correctly to one another and the unit. 
If they are, remove the patches from your skin check 
“stickiness” of the patches and add 1-2 drops of water if 
needed. Then, reapply the patches to the skin. If there still isn’t 
a good response from the machine, or the patches were very 
“sticky” replace the patches with a new set. 
b. 
If the error message still appears when you turn on the 
machine, then call the research assistant and report the 
problem.  
If the unit powers on but the intensity cannot be changed, try unlocking 
the device (page 5 section #8).  
If the unit is damaged or if it is not working correctly call the research 
assistant. Do not attempt to repair or use the unit.