Neuromuscular Electrical Stimulation in Heart Failure Patients to Improve Functional Recovery Following Hospitalization (NeuHF-Recover)
Phase: NA
Conditions: Heart Failure With Preserved Ejection Fraction
Sponsor: University of Vermont Medical Center

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Human Subjects Research Protocol Form 07/01/15 
 
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Human Subjects Research Protocol  
 
The Common Human Subjects Protocol Cover Form must be completed and attached to the front of this form. This Protocol 
form should be completed for any human subjects research proposal that does not have a specific “protocol,” such as a grant 
application.  This form must be submitted along with a copy of the complete grant proposal and all the information in this form 
must be consistent with that proposal.  This protocol form, once IRB approved, will be the working protocol for that research.  
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PROTOCOL SUMMARY 
 
Project Title: 
Protocol 
Version 
Date: 
Neuromuscular Electrical Stimulation in Heart Failure Patients to Improve Functional Recovery Following 
Hospitalization (NeuHF-Recover). 
11/30/2023  
 
 
Principal Investigator:   
Sherrie Khadanga 
 
Grant Sponsor: 
Department of Medicine 
Grant  Number: 
Not applicable 
                                                                                              (For grants routed through UVM, indicate the OSP Proposal ID # 
                                                                                                 located at the top of the OSP Routing Form) 
 
 
Lay Language Summary:  (Please use non-technical language that would be understood by nonscientific IRB members to 
summarize the proposed research project.  The information must include: (1) a brief statement of the problem and related 
theory supporting the intent of the study, and (2) a brief but specific description of the procedure(s) involving the human 
subjects.  Please do not exceed one single-spaced 8 ½ X 11” page.) 
 
Heart failure (HF) is the leading cause of hospitalization among adults in the US,1,2 with patients with 
preserved ejection fraction (HFpEF), defined as EF>50% and patients with moderate to reduced 
ejection fraction (<50%)Approximately 20% of HFpEF patients will be re-admitted within 30 days and 
>50% within 1 year, with increased risk of mortality.2,3 While most research has focused on HF with 
reduced EF<40% (HFrEF), patients with HFpEF have higher rates of outpatient and ED visits.3 Despite 
high rates of mortality and health care utilization, there is no proven treatment for HFpEF and, as 
readmissions and ED visits suggest, there is gap in their transition of care post hospitalization. 
Chronic fatigue, exercise intolerance and an inability to perform activities of daily living are hallmark 
symptoms of HF that negatively impact quality of life and prognosis.4Physical disability is exacerbated 
by hospitalization, in which bed rest can cause acute muscle loss and further disability.5,6 The 
importance of hospital-acquired disability is underscored by the fact that reduced mobility at hospital 
discharge is predictive of 30 d readmissions.7 Even after acute HF symptoms resolve, many patients 
experience deficits in strength, balance and mobility and some never regain baseline function.6 Exercise 
training is beneficial in improving physical function in these patients, but classical exercise training is 
difficult during the acute post-phase discharge and cardiac rehabilitation is not covered for HFpEF 
patients.6,8 Many HF studies have focused on guideline directed medical therapy, however, few have 
focused on rehabilitation following hospitalization.8  
A home based exercise intervention following hospital discharge may improve physical functional 
recovery, but there are numerous barriers to home exercise in HF patients. Neuromuscular electrical 
stimulation (NMES) offers a potential solution to these barriers, as it confers an exercise training effect 
without the physical requirements of traditional exercise. NMES is an inexpensive, safe, FDA- approved 
intervention which allows non-volitional initiation of muscle contractions that mimic resistance or aerobic 
type exercise, leading to training responses similar to traditional exercise.9 In older adults with chronic 
 
The University of Vermont Committees on Human Research 
 
 
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disease, including HF patients, NMES improves muscle strength, but its ability to improve physical 
function is equivocal.10 Additionally, these studies were small and mostly performed in the outpatient 
setting with stable HFrEF patients without recent hospitalization.11 Thus, whether NMES is effective in 
HFpEF and HFrEF patients at improving functional recovery following the acute disabling effects of 
hospitalization is unclear.9-11  
The purpose of this phase 4 randomized controlled trial is to establish the feasibility and efficacy of 
NMES administered to the quadriceps muscles to improve early functional recovery in older heart failure 
patients recently hospitalized for HF. Functional status will be objectively measured via the 6-minute 
walk test (6MW) and Short Physical Performance Battery tests (SPPB). Based on our pilot results in 
patients undergoing cardiac surgery, we hypothesize that the use of NMES will improve functional 
recovery.12 Successful completion of this study will provide seminal data regarding the utility of NMES to 
improve functional capacity following hospitalization in heart failure patients, which may have 
implications for both readmission and long term prognosis 
 
PURPOSE AND OBJECTIVES   
 
Purpose:  The importance of the research and the potential knowledge to be gained should be explained in detail.  Give 
background information.  
As the US population ages, there has been a rise in patients experiencing heart failure and, in turn, 
hospitalizations and readmissions.2,3 Focus has been placed on transitional care services for medical 
and surgical treatments, with little attention on physical rehabilitation services, despite the fact that 
patients prioritize this as an outcome of their treatment and that physical disability increases risk of 
complications and readmission.5-7 After hospitalization, HFpEF patients are severely deconditioned, but 
HFpEF is not a qualifying diagnosis for outpatient cardiac rehabilitation (CR). Our intervention aims to 
overcome this gap in rehabilitative care early after hospital discharge to improve functional recovery.  
NMES is an innovative modality to bridge the critical gap in transition of care for these patients. 
Numerous trials have found that NMES improves muscle strength in stable HFrEF patients, but its 
effects on physical function are equivocal and only 1 small study examined NMES in clinically stable 
outpatient HFpEF patients.8-10To our knowledge, the proposed study would be the first to investigate the 
utility of NMES to improve functional recovery in heart failure patients following hospitalization. Our 
rationale for targeting this period is based on our work in cardiac surgical patients, where functional 
gains during recovery after hospitalization were substantial, but also because regaining functional 
capacity during this period is important for long-term disability and clinical outcomes.11,12  
Results from this study can advance our existing treatment of heart failure in several ways. First, it 
will provide evidence of a novel rehabilitation intervention to improve functional status after a disabling 
event, such as hospitalization. With the exception of our own work, virtually no studies have examined 
NMES in the acute, post-discharge setting. Secondly, it may improve health outcomes given that 
hospital-acquired disability/decondition increases risk of complications and readmissions.11,12 Vermont’s 
rural environment makes it challenging for patients to access medical care and rehabilitation. Our 
proposed study is conceptually innovative in developing a transitional rehabilitative intervention to 
address an important sector of older cardiac patients prone to hospital-acquired disability and 
rehospitalization. At this time, HFpEF patients are not eligible for CR and HFrEF patients must wait 6 
weeks before CR enrollment, therefore, NMES can provide a portable, high value, home-based 
intervention to aid in the recovery of physical function for heart failure patients recently discharged from 
the hospital.. Few studies have assessed the utility of NMES to improve functional recovery following an 
acute, disabling event.8-10,13 If successful, our data could advance a new model for early post-
hospitalization rehabilitation. 
 
References. Include references to prior human or animal research and references that are relevant to the design and conduct 
of the study. 
References 
1. Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection 
fraction. Nat Rev Cardiol. 2017;14(10):591-602. 

Research Protections Office, 213 Waterman Bldg, 85 South Prospect St, Burlington, VT 05405, (802) 656-5040 
Human Subjects Research Protocol Form 07/01/15 
 
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2. Bello NA, Claggett B, Desai AS, et al. Influence of previous heart failure hospitalization on 
cardiovascular events in patients with reduced and preserved ejection fraction. Circ Heart Fail. 
2014;7(4):590-595. doi:10.1161/CIRCHEARTFAILURE.113.001281 
3. Nichols GA, Reynolds K, Kimes TM, Rosales AG, Chan WW. Comparison of Risk of Re-
hospitalization, All-Cause Mortality, and Medical Care Resource Utilization in Patients With Heart 
Failure and Preserved Versus Reduced Ejection Fraction. Am J Cardiol. 2015;116(7):1088-1092. 
4. Aggarwal M, Bozkurt B, Panjrath G, Aggarwal B, Ostfeld RJ, Barnard ND, Gaggin H, Freeman 
AM, Allen K, Madan S, Massera D, Litwin SE; American College of Cardiology’s Nutrition and 
Lifestyle Committee of the Prevention of Cardiovascular Disease Council. Lifestyle Modifications 
for Preventing and Treating Heart Failure. J Am Coll Cardiol. 2018 Nov 6;72(19):2391-2405 
5. Reeves GR, Whellan DJ, Duncan P, et al. Rehabilitation Therapy in Older Acute Heart Failure 
Patients (REHAB-HF) trial: Design and rationale. Am Heart J. 2017;185:130-139 
6. Fisher SR, Kuo YF, Sharma G, et al. Mobility after hospital discharge as a marker for 30-day 
readmission. J Gerontol A Biol Sci Med Sci. 2013;68(7):805-810 
7. Reeves GR, Whellan DJ, Patel MJ, et al. Comparison of Frequency of Frailty and Severely 
Impaired Physical Function in Patients ≥60 Years Hospitalized With Acute Decompensated 
Heart Failure Versus Chronic Stable Heart Failure With Reduced and Preserved Left Ventricular 
Ejection Fraction. Am J Cardiol. 2016;117(12):1953-1958. 
8. Langeard A, Bigot L, Chastan N, Gauthier A. Does neuromuscular electrical stimulation training 
of the lower limb have functional effects on the elderly?: A systematic review. Exp Gerontol. 
2017;91:88-98 
9. Ploesteanu RL, Nechita AC, Turcu D, Manolescu BN, Stamate SC, Berteanu M. Effects of 
neuromuscular electrical stimulation in patients with heart failure - review. J Med Life. 
2018;11(2):107-118. 
10. Smart NA, Dieberg G, Giallauria F. Functional electrical stimulation for chronic heart failure: a 
meta-analysis. Int J Cardiol. 2013;167(1):80-86 
11. Rengo JL, Savage PD, Barrett T, Ades PA. Cardiac Rehabilitation Participation Rates and 
Outcomes for Patients With Heart Failure. J Cardiopulm Rehabil Prev. 2018;38(1):38-42  
12. Fried TR, McGraw S, Agostini JV, Tinetti ME. Views of older persons with multiple morbidities on 
competing outcomes and clinical decision-making. J Am Geriatr Soc. 2008;56(10):1839-1844. 
13. Karavidas A, Driva M, Parissis JT, et al. Functional electrical stimulation of peripheral muscles 
improves endothelial function and clinical and emotional status in heart failure patients with 
preserved left ventricular ejection fraction. Am Heart J. 2013;166(4):760-767. 
14. Houghton PE, Nussbaum EL, and Hoens AM. ELECTROPHYSICAL AGENTS - 
Contraindications And Precautions: An Evidence-Based Approach To Clinical Decision Making 
In Physical Therapy. Physiother Can. 2010;62(5):1-80. 
15. Brochu M, Savage P, Lee M, et al. Effects of resistance training on physical function in older 
disabled women with coronary heart disease. J Appl Physiol (1985). 2002;92(2):672-678. 
16. McHorney CA, Ware JE Jr, Lu JF, Sherbourne CD. The MOS 36-item Short-Form Health Survey 
(SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient 
groups. Med Care. 1994;32:40–66 
17. Green CP, Porter CB, Bresnahan DR, Spertus JA. Development and evaluation of the Kansas 
City Cardiomyopathy Questionnaire: a new health status measure for heart failure. J Am Coll 
Cardiol. 2000;35(5):1245-1255. 
18. Gremeaux V, Troisgros O, Benaïm S, et al. Determining the minimal clinically important 
difference for the six-minute walk test and the 200-meter fast-walk test during cardiac 
rehabilitation program in coronary artery disease patients after acute coronary syndrome. Arch 
Phys Med Rehabil. 2011;92(4):611-619. 
 
 
Objectives:  Clearly state the primary and secondary objective(s) of the study. 

Research Protections Office, 213 Waterman Bldg, 85 South Prospect St, Burlington, VT 05405, (802) 656-5040 
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Patients with heart failure have high rates of hospitalization and mortality. Unfortunately, there is lack 
of evidence based therapies for this cohort. While exercise improves clinical status in patients with 
HFpEF, these patients are often severely deconditioned and have difficulty engaging in traditional 
exercise programs. This deconditioning typically evolves during hospitalization, when disease 
exacerbation and treatments conspire with physical inactivity to cause skeletal muscle deconditioning. 
Failure to remediate lost functional capacity contributes to worsened symptoms and greater risk for 
disability.  Neuromuscular electrical stimulation (NMES) of the lower extremity has proven to be an 
alternative to physical exercise and can serve as a bridge for heart failure patients to regain strength and 
improve functional status following hospitalization. The proposed studies will assess the efficacy of a 
novel rehabilitation intervention to improve functional recovery after a disabling event specifically 
hospitalization in older heart failure patients.  
Primary Aim: Determine whether NMES of the lower extremity musculature improves physical 
functional recovery in older heart failure patients recently hospitalized for congestive heart failure. We 
hypothesize that NMES will improve recovery of physical function compared to the control. 
 
Secondary Aim: Define the effects of NMES on self-reported physical function and quality of life at 4 
weeks from baseline. We hypothesize that NMES will improve quality of life and self-reported 
physical function compared to the control.  
 
METHODS AND PROCEDURES  
 
Study Design: Describe the research design, including a description of any new methodology and its advantage over existing 
methodologies.   
Study design: We will use a randomized-controlled trial design. Patients admitted for heart failure will be 
recruited and randomized to NMES or control for 4 weeks following hospital discharge. Patients will be 
stratified by sex and age. Baseline testing will occur prior to discharge and consist of functional 
assessment by 6MW and SPPB and completion of 2 questionnaires regarding quality of life and physical 
function (Kansas City Cardiomyopathy questionnaire {KCCQ} and (Medical Outcomes Study Short 
Form-36 {MOS SF-36}). After completion of the 4 week intervention period, patients will undergo Post-
Testing which will be identical to Baseline testing.  
 
Inclusion/Exclusion Criteria: Patients will be recruited if they: 1) have clinical diagnosis of heart faliure 
being actively managed during hospitalization, 2) live within 30 miles of UVMMC and are between 50-90 
years of age. Patients will be excluded if they have: 1) severe dementia/alzheimer’s disease 2)an active 
malignancy, excluding non-melanoma skin cancer or low-grade prostate cancer under active 
surveillance; 3) exercise-limiting vascular or neuromuscular disease; 4) body mass index ≥40 kg/m2 or 
5*) an existing lower extremity blood clot or implantable cardioverter-defibrillator (ICD) or pacemaker 
(PPM).14 *The last criteria is a contraindication for NMES and we will withdraw patients if they develop a 
blood clot or receive an ICD or PPM.  
 
Randomization and blinding:  Patients will be randomized prior to hospital discharge to NMES or control 
using Pocock and Simon’s covariate-adaptive randomization for which sex and age will be stratified. The 
unblinded project manager will train patients to use NMES device and oversee them during the 
intervention. The PI and co-I will be blinded to treatment assignment. 
 
Interventions:  
Usual care: Patients will not receive an NMES device. We opted not to use “sham” stimulation (eg, low-
intensity stimulation below the threshold to initiate contraction) lessen the chance that patients may 
increase stimulation to produce contractions if there is perceived benefit. Patients will be contacted 
weekly to assess overall recovery. As there is currently no standard of care rehabilitation for these 
patients following discharge and NMES does not have demonstrated benefits, our study meets the 
requirements for clinical equipoise. 
 

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NMES: NMES will be carried out bilaterally on the quadriceps using a portable stimulator. Two adhesive 
electrodes will be placed to the anterior surface of each thigh. Symmetrical, biphasic pulses (400 μs 
duration at 25 Hz) will be used, with a duty cycle of 25% (10 s on, 30 s off). Patients will be trained to 
conduct NMES sessions and will select stimulation intensities sufficient to cause visible muscle 
contractions below their pain threshold. Training in the use of the NMES device will begin prior to 
hospital discharge. After discharge, NMES sessions will occur 5 d/wk once per day for 45 min per 
occasion (5 min low-intensity warm-up, 40 min higher-intensity stimulation) for 4 wks. This program is 
meant to mimic an aerobic-type exercise stimulus and similar to prior protocols. Daily logs and weekly 
phone calls will be used to monitor compliance to maximize intervention fidelity with overall compliance 
measured using the device software.  
 
Outcomes: The primary outcome is 6MW. Functional capacity measures and quality of life measures will 
be obtained at baseline (prior to hospital discharge) and at 4 weeks. 
1. Baseline characteristics including age, body mass index, length of hospital stay, medications, 
and smoking status 
2. Functional Capacity measures: 
a. 6-MW test is a well-validated method to assess functional capacity in patients with 
cardiac disease and shows convergent validity with other indices of physical function The 
test will be conducted under standardized conditions, as described by us.11,15 Distance 
walked (m) will be the primary outcome. 
b. SPPB will be measured, as it is a widely used, easy to measure index of physical function 
in older adults. Thus, it provides context for the severity of disability in our population and 
the modifying effects of NMES for comparison to other studies.11 
3. Quality of Life measures: 
a. Self-reported physical functioning assessment using the Medical Outcomes Study Short 
Form-36 (MOS SF-36) survey questionnaire (0-100 scale) with 100 representing 
excellent physical functioning16 
b. Kansas City Cardiomyopathy questionnaire17 
4. Hospital readmission and Emergency Department visits within 3 months 
     5.    Activities of Daily Living measures:  
                  a. Lawton Brody ADL questionnaire 
                  b. Katz Index of Independence in Activities of Daily Living 
 
Procedures:  Describe all procedures (sequentially) to which human participants will be subjected. Identify all procedures that 
are considered experimental and/or procedures performed exclusively for research purposes. Describe the types, frequency 
and duration of tests, study visits, interviews, questionnaires, etc.   Include required screening procedures performed before 
enrollment and while on study. Please provide in table, list or outline format for ease of review. (describe and attach all 
instruments) 
 
Note: A clinical research protocol may involve interventions that are strictly experimental or it may involve some aspect of 
research (e.g., randomization among standard treatments for collection and analysis of routine clinical data for research 
purposes). It is important for this section to distinguish between interventions that are experimental and/or carried out for 
research purposes versus those procedures that are considered standard therapy. In addition, routine procedures performed 
solely for research purposes (e.g., additional diagnostic/follow-up tests) should be identified. 
All of the procedures and interventions on volunteers recruited for these studies are carried out solely for 
research purposes, as none are part of standard therapy in heart failure patients. 
Physiological Testing (Discharge and 1  month post discharge) 
SPPB will be measured, as described by us (1), as this assessment is prognostic for functional 
competence and mortality in cardiac surgical patients (2). This measure takes ~5 min to perform and 
is comprised of: 5 repeated chair stands, balance testing (3 tasks each 10 s long) and a   4 meter 
walk. As increasing SPPB score in the first month post-discharge in a sample of elderly patients with 
diverse clinical backgrounds was associated with lower risk for rehospitalization and death (3), 
improvements in, or maintenance of, this metric would provide strong evidence for the clinical utility 
of NMES. We have experience with this measure in cardiac populations (4). 
6 MW was developed to assess cardiopulmonary fitness in patients with lung and cardiac disease 

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(5), but has been used widely to assess disability in older adults (6) and is the most common metric 
used when seeking FDA approval for interventions to improve physical function. We have 
experience with this measure in heart failure patients (7). 
Treatment phase 
NMES will be carried out bilaterally on the quadriceps using a portable stimulator (EMPI Continuum). 
Two adhesive electrodes will be affixed to the anterior surface of each thigh: ~1 cm distal to the inguinal 
crease and ~5 cm proximal to the patella, just lateral to the midline of the thigh to assure that it does not 
interfere with incisions for vein harvest. Symmetrical, biphasic pulses (400 µs duration at 25 Hz) will be 
used, with a duty cycle of 25% (10 s on, 30 s off). Patients will be trained to conduct NMES sessions 
and will select stimulation intensities sufficient to cause visible muscle contractions below their pain 
threshold. Training in the use of the NMES device will begin prior to day of discharge. . This training will 
consist of one session per day of ~15 min to familiarize the volunteer with the unit and the 
exercise/contraction stimulus. Upon discharge, NMES sessions will occur 5 d/wk once per day for 45 
min per occasion (5 min low-intensity warm-up, 40 min higher-intensity stimulation) for 4 wks. This 
program is meant to mimic an aerobic-type exercise stimulus (8) and has been shown in heart failure 
patients to have functional benefits over a similar treatment period (9, 10). We acknowledge that the 
NMES training load is substantial, but have modeled this program on others that have shown 
morphological and functional effects in heart failure patients (11). At this exploratory stage, we feel that it 
is essential to use a stimulus that affects muscle size and function, with future studies modifying the 
NMES dose to establish a threshold that elicits a training effect with the highest subject compliance rate. 
Daily logs and weekly phone contacts will be used to track compliance, and compliance will be covertly 
monitored using the device software.  
Control patients will not receive an NMES device. We chose not to utilize a control NMES intervention 
(eg, stimulation below threshold to elicit contraction) to mitigate the possibility that patients may increase 
stimulation to produce muscle contractions if there is perceived benefit. Rigorous control over the NMES 
stimulus is preferable to controlling for any effects of sub-threshold, cutaneous electrical stimulation. 
Patients will be contacted weekly to assess their recovery and discuss issues related to general health 
to equate the degree of interaction with study personnel to that of the NMES intervention group. 
 
Quality of Life measures: will be assessed with the following questionnaires which will be obtained at 
baseline (discharge) and 1 month following discharge 
a. Self-reported physical functioning assessment using the Medical Outcomes Study Short 
Form-36 (MOS SF-36) survey questionnaire (0-100 scale) with 100 representing 
excellent physical functioning 
b. Kansas City Cardiomyopathy questionnaire 
Activities of Daily Living measures:  
                  a. Lawton Brody ADL questionnaire 
                  b. Katz Index of Independence in Activities of Daily Living 
 
References cited above: 
1. 
Ades, P. A., Savage, P. D., Cress, M. E., Brochu, M., Lee, N. M., and Poehlman, E. T. (2003) Resistance training on 
physical performance in disabled older female cardiac patients. Med Sci Sports Exerc 35, 1265-1270 
2. 
Afilalo, J., Eisenberg, M. J., Morin, J.-F., Bergman, H., Monette, J., Noiseux, N., Perrault, L. P., Alexander, K. P., 
Langlois, Y., Dendukuri, N., Chamoun, P., Kasparian, G., Robichaud, S., Gharacholou, S. M., and Boivin, J.-F. (2010) 
Gait speed as an incremental predictor of mortality and major morbidity in elderly patients undergoing cardiac surgery. 
J Am Coll Cardiol 56, 1668-1676 
3. 
Volpato, S., Cavalieri, M., Sioulis, F., Guerra, G., Maraldi, C., Zuliani, G., Fellin, R., and Guralnik, J. M. (2011) 
Predictive value of the short physical performance battery following hospitalization in older patients. J Gerontol A Biol 
Sci Med Sci 66A, 89-96 
4. 
Rengo, J. L., Savage, P. D., and Ades, P. A. (in press) Directly measured physical function in cardiac rehabilitation. J 
Cardiopulm Rehabil Prev  
5. 
Guyatt, G. H., Sullivan, M. J., Thompson, P. J., Fallen, E. L., Pugsley, S. O., Taylor, D. W., and Berman, L. B. (1985) 
The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J 132, 
919-923 
6. 
Bean, J. F., Kiely, D. K., Leveille, S. G., Herman, S., Huynh, C., Fielding, R., and Frontera, W. R. (2002) The 6-minute 
walk test in mobility-limited elders: what is being measured? J Gerontol 57A, M751-M756 
7. 
Savage, P. D., Shaw, A. O., Miller, M. S., VanBuren, P., LeWinter, M. M., Ades, P. A., and Toth, M. J. (2011) Effect of 
resistance training on physical disability in chronic heart failure. Med Sci Sports Exer 43, 1379-1386 

Research Protections Office, 213 Waterman Bldg, 85 South Prospect St, Burlington, VT 05405, (802) 656-5040 
Human Subjects Research Protocol Form 07/01/15 
 
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8. 
Atherton, P. J., Babraj, J. A., Smith, K., Singh, J., Rennie, M. J., and Wackerhage, H. (2005) Selective activation of 
AMPK-PGC-1α or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance 
training-like electrical muscle stimulation. FASEB J 19, 786-788 
9. 
Harris, S., LeMaitre, J. P., Mackenzie, G., Fox, K. A. A., and Denvir, M. A. (2003) A randomised study of home-based 
electrical stimulation of the legs and conventional bicycle exercise training for patients with chronic heart failure. Eur 
Heart J 24, 871-878 
10. 
Karavidas, A., Parissis, J. T., Matzaraki, V., Arapi, S., Varounis, C., Ikonomidis, I., Grillias, P., Paraskevaidis, I., 
Pirgakis, V., Filippatos, G., and Kremastinos, D. T. (2010) Functional electrical stimulation is more effective in severe 
symptomatic heart failure patients and improves their adherence to rehabilitation programs. J Card Fail 16, 244-249 
11. 
Karavidas, A., Arapi, S., Pyrgakis, V., and Adamopoulos, S. (2010) Functional electrical stimulation of lower limbs in 
patients with chronic heart failure. Heart Fail Rev 15, 563-579 
12.         Toth MJ, Miller MS, VanBuren P, et al. Resistance training alters skeletal muscle structure and function in human heart 
failure: effects at the tissue, cellular and molecular levels. J Physiol. 590:1243-1259, 2012. 
For research involving survey, questionnaires, etc.:  Describe the setting and the mode of administering the instrument and 
the provisions for maintaining privacy and confidentiality.  Include the duration, intervals of administration, and overall length of 
participation. (describe and attach all instruments) 
 
Not applicable 
 
We will assess physical functionality/quality of life with the MOS-SF36 questionnaire and KCCQ. This 
questionnaire takes about ~10 min to complete and will be completed at Discharge and 4 wk Post-
hospitalization discharge  
Statistical Considerations: Delineate the precise outcomes to be measured and analyzed. Describe how these results will be 
measured and statistically analyzed. Delineate methods used to estimate the required number of subjects. Describe power 
calculations if the study involves comparisons.  Perform this analysis on each of the primary and secondary objectives, if 
possible.  
Statistical Analysis:  
Primary outcome is the 6MW. Other outcomes include SPPB, KCCQ and MOS SF-36 questionnaire 
results and subsequent ER visits and hospitalizations. The two experimental groups will be compared 
on baseline demographic characteristics using one-way Analysis of Variance (ANOVA) for continuous 
measures and chi-square tests (or Fisher’s Exact Test) for categorical variables. Our primary outcome is 
to assess changes in physical function (specifically 6MW) between study groups to test whether NMES 
improves functional recovery from discharge to 4 weeks. We will use analysis of covariance to model 
primary and secondary outcomes, as this is the preferred model to assess data in pre-post RCTs. In this 
model, the 4-week post-discharge value is the dependent variable and the value at hospital discharge is 
a covariate. Sex interactions for response to NMES will be examined. We will assess QOL by 
questionnaires to determine if NMES improves patient-reported QOL vs. usual care. Clinical and other 
factors that may modify the response to NMES (eg, length of stay, etc) can be included in the model to 
control for potential confounders that might differ by group in the event that randomization fails to equate 
groups. 
 
Sample Size Calculation:  
The proposed sample of 60 participants is based on having sufficient power to calculate differences 
in our primary outcome (6MW) between the control condition and the intervention and accommodating 
for potential drop outs (20%) from the study.11 Power is estimated to be 80% to detect a difference in the 
change in 6MW between the 2 groups at the p<0.05 level. These estimates are based on data from a 
meta-analysis of RCTs of NMES in stable patients with chronic heart failure which detected a difference 
of 47 m between NMES group vs placebo as well as our pilot data of CABG patients, where patients 
randomized to NMES increased 6-MW distance 73 m further than controls.11 We assume a 6-MW 
distance of 250 ± 60 m (mean ± SD) at hospital discharge in both groups. Additionally, we have reduced 
the improvement in 6-MW distance in the NMES group by ~30% to 50 m (6-week post-discharge NMES: 
250 ± 60 m vs. Control: 300± 60 m) to be conservative. This magnitude improvement in 6-MW is similar 
to meaningful changes found in 6-MW performance in older adults with mild- to moderate mobility 
disability undergoing home-based strength training (47 m) and is twice the minimal clinically significant 
difference in patients with cardiac disease following CR (25 m).18 Therefore, we will need to recruit 60 
patients with our target of 48 patients to complete the study (n=24/group), assuming a drop out of 20%. 
We have not performed sample size estimates for SPPB or secondary outcomes, as extrapolating the 
ability of NMES to affect other variables is challenging barring relevant preliminary data, particularly in 
recently hospitalized heart failure patients. 
 

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Risks/Benefits:  Describe any potential or known risks.  This includes physical, psychological, social, legal or other risks.  
Estimate the probability that given risk may occur, its severity and potential reversibility.  If the study involves a placebo or 
washout period, the risks related to these must be addressed in both the protocol and consent.  Describe the planned 
procedures for protecting against or minimizing potential risks and assess their likely effectiveness.  Where appropriate, discuss 
plans for ensuring necessary medical or professional intervention in the event of adverse effects to the subjects.   Discuss the 
potential benefits of the research to the subjects and others.  Discuss why the risks to the subjects are reasonable in relation to 
the anticipated benefits to subjects and others.  Discuss the importance of the knowledge gained or to be gained as a result of 
the proposed research and why the risks are reasonable in relation to the knowledge that reasonably may result.  If there are 
no benefits state so. 
Potential risks: Below we have highlighted those procedures/measurements that have anything greater 
than negligible risk to the volunteers’ health for each phase of the study.  
Testing: Risks associated with functional testing are minimal. All of the activities are similar to those 
performed during the conduct of normal daily activities. If volunteers are unable to do any of the 
activities because of limitations of their heart condition, they will not be required to perform them and 
testing will be monitored by trained personnel.  
 
NMES intervention: NMES is a generally safe procedure, delivered in the proposed study by an FDA 
approved device. Although evidence is limited, some have suggested that NMES could increase the risk 
of DVT, which may have serious health consequences. However, several published reports show that 
NMES significantly reduces the risk of developing deep vein thromboses (DVT) (1) and we will actively 
exclude any individual with a known coagulopathy. Because of the location of the stimulating electrodes 
(upper leg), the risk of NMES dislodging a DVT is likely minimal. We will also exclude any volunteers 
that currently have an implanted cardiac defibrillator or pacemaker, as this is contraindicated for NMES 
use (1). Patients may experience some painful muscle contractions as they first adjust the stimulus to a 
tolerable level, which can be quickly corrected by reducing the stimulation intensity. After treatment, 
muscles soreness may occur. The level of fatigue and/or soreness, however, will be similar to that which 
occurs following a standard exercise training session and should dissipate over time as the volunteer’s 
muscles become accustomed to the electrically-stimulated contractions (ie, they become trained).  
  
Benefits: The direct benefit of the research to volunteers is minimal. NMES may improve skeletal 
muscle structure or function and, in turn, improve physical functional capacity. Because of this, patients 
may experience improved physiological capacity, which could reduce disability. If we find that NMES 
has beneficial effects on physical function, further research and application of the technique to heart 
failure patients may assist in the development of more effective transitional rehabilitative care 
approaches to mitigate long-term functional morbidity. 
References cited above: 
1. 
Houghton, P. E., Nussbaum, E. L., and Hoens, A. M. (2010) Electrophysical agents. Contraindications and 
precautions: an evidence-based approach to clinical decision making in physical therapy. Physiother Can 62, 1-80 
. 
 
Therapeutic Alternatives:  List the therapeutic alternatives that are reasonably available that may be of benefit to the potential 
subject and include in the consent form as well. 
 
Not Applicable 
There are no alternative rehabilitation regimens during the early, post-hospitalization period for heart 
failure patients.  
Data Safety and Monitoring:  The specific design of a Data and Safety Monitoring Plan (DSMP) for a protocol may vary 
extensively depending on the potential risks, size, and complexity of the research study.  For a minimal risk study, a DSMP 
could be as simple as a description of the Principal Investigator’s plan for monitoring the data and performance of safety 
reviews or it could be as complex as the initiation of an external, independent Data Safety and Monitoring Board (DSMB). The 
UVM/UVM Medical Center process for review of adverse events should be included in the DSMP.   
Drs. Khadanga and Toth will monitor the safety of the research procedures for this study. We have 
not set up a formal safety committee for several reasons. First, the PIs and the investigative team have 
a long history of performing the measurements proposed in this proposal. The procedures carry 
relatively low risk to the volunteers. Second, because of the small number of patients and track record of 
performing these procedures, it is highly unlikely that we will need to "stop" the study or significantly 

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alter the procedures. If any problems/unanticipated events arise related to the NMES intervention, Dr. 
Khadanga will determine the nature of the problem and its relatedness to the NMES intervention and 
decide whether continued participation in the study is in the best interest of the patient. As detailed 
above, however, NMES is FDA-approved for this indication and we have taken precautions to minimize 
the potential for adverse effects. 
 
Adverse Event and Unanticipated Problem (UAP) Reporting:  Describe how events and UAPs will be evaluated and 
reported to the IRB.  All protocols should specify that, in the absence of more stringent reporting requirements, the guidelines 
established in the Committees on Human Research “Adverse Event and Unanticipated Problems Reporting Policy” will be 
followed.  The UVM/UVM Medical Center process for review of adverse events and UAPs to subjects or others should be 
included in the DSMP.   
The PIs or the study coordinator (Jason Rengo) will monitor the safety of the research 
procedures/interventions for this study. Mr. Rengo or Dr. Khadanga will be available on-site for all 
assessments that may pose safety concerns for volunteers. Additionally, subjects will be contacted 
weekly to review device use and any difficulty or issues that may have occurred since the last contact. 
General muscle soreness is expected in some subjects and will not be considered an adverse event. 
Subjects reporting severe muscle discomfort limiting daily activity or other potential adverse events (i.e. 
skin irritation) will be instructed to discontinue device use pending further review. In this context, study 
personnel will be readily available to monitor volunteer safety throughout the study. If an event occurs 
that affects participant safety, Mr. Rengo will alert Dr. Khadanga, who will adjudicate the event with 
respect to its severity, expectedness and relatedness to participation in the study. Because numerous 
studies in our laboratories and others have demonstrated the safety of this regimen of testing in patients 
from with a broad range of clinical backgrounds (eg, heart failure patients, cancer patients, advanced-
stage, knee OA patients; healthy elderly), we expect minimal problems related to testing or the 
intervention. Considering the low risk nature of these studies, we have not incorporated "stoppage 
criteria" for the overall study. Instead, Dr. Khadanga will decide whether an individual participant should 
continue with the study following occurrence of any adverse events or unanticipated problems, taking 
into consideration what is in the best interest of each individual patient. 
Adverse events will be reported by one of 3 mechanisms. First, the joint University of 
Vermont/University of Vermont Medical Center (UVMMC) Committee for Human Subject Research 
Adverse Event Reporting Document. These reports will be sent to the office of the Committee for 
Human Research in the Medical Science (CHRMS) within 2 days of the event. Reporting any adverse 
events will be the responsibility of the PIs. The CHRMS will make a determination as to whether 
additional reporting requirements are indicated. Additionally, the UVMMC Patient Safety Reporting 
system (SAFE), which may be initiated by health care center staff or study personnel. These forms will 
be forwarded within 3 days to the PI, UVMMC Risk Management Office, CHRMS and other appropriate 
agencies, as indicated by the nature of the report. Reviews of protocol specific adverse events will be 
performed no less than annually. Additionally, any adverse event that occurs will be forwarded to the PIs 
for reporting to the Human Subject Research Protection Office within 1 week of occurrence. Of note, 
these protections against risk include both physical risks to the volunteers, as well as risks associated 
with any breach in confidentiality. 
On an annual basis, Drs. Toth and Khadanga will assess data being gathered and safety of 
volunteers to assess the pattern or frequency of events to identify occurrence of any event or problem 
that alters the safety profile of the procedures being performed. The exception would be occurrence of a 
serious adverse event or unanticipated problem that necessitates re-evaluation of the expected risk of 
the study procedures at an earlier time point. Additionally, they will evaluate data collection and storage 
to ensure the confidentiality of data and quality. Each of these evaluations will be followed by reports of 
study progress and patient safety to the University of Vermont CHRMS via yearly progress reports.  
Withdrawal Procedures:  Define the precise criteria for withdrawing subjects from the study.   Include a description of study 
requirements for when a subject withdraws him or herself from the study (if applicable). 
Volunteers will be withdrawn if the research team, clinician and/or safety officer feels that further 
participation in the study or performance of any procedure associated with this study would, in any way, 
put the volunteer at undue risk or not be in their best interest. Moreover, volunteers may be withdrawn if 
s/he fails to attend scheduled visits or do not comply with instructions from research staff. 

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Sources of Materials:  Identify sources of research material obtained from individually identifiable human subjects in the form 
of specimens, records or data.  Indicate whether the material or data will be obtained specifically for research purposes or 
whether use will be made of existing specimens, records or data. 
An individual research record will be kept on each volunteer in compliance with HIPAA standards. This 
record will contain identifying data, demographic information and results from all clinical research 
measurements and evaluations. The results of all testing will be kept confidential. All materials gathered 
in conjunction with the proposed studies will be used for research purposes only and will be available 
only to research personnel working on these studies, who have obtained proper training in human 
subjects research and privacy protection.  
 
DRUG AND DEVICE INFORMATION  
 
Investigators are encouraged to consult the UVM Medical Center Investigational Pharmacy Drug Service (847-4863) prior to 
finalizing study drug/substance procedures. 
 
Drug (s) 
X 
Not applicable 
Drug name – generic followed by brand name and common abbreviations. Availability – Source and pharmacology; vial or 
product sizes and supplier.  If a placebo will be used, identify its contents and source. (attach investigational drug brochure) 
 
Preparation:  Reconstitution instructions; preparation of a sterile product, compounded dosage form; mixing guidelines, 
including fluid and volume required.  Identify who will prepare. 
 
Storage and stability – for both intact and mixed products.   
 
Administration – Describe acceptable routes and methods of administration and any associated risks of administration. 
 
Toxicity – Accurate but concise listings of major toxicities.  Rare toxicities, which may be severe, should be included by 
indicated incidence.  Also adverse interactions with other drugs used in the protocol regimen as well as specific foods should 
be noted.  Address significant drug or drug/food interactions in the consent form as well.  List all with above details. 
 
Is it FDA approved: (include FDA IND Number) 
1.  in the dosage form specified?  If no, provide justification for proposed use and source of the study drug in that form. 
 
2.  for the route of administration specified?  If no, provide justification for route and describe the method to accomplish. 
 
3.  for the intended action? 
 
 
Device (s) 
 
Not applicable 
Device name and indications (attach investigational device brochure) 
The interventional device used in this study: EMPI Continuum complete electrotherapy system has 
received FDA approval (501K: K093324) for retarding disuse-related atrophy, which we believe is one of 
the primary mechanisms whereby HFpEF patients become more functional disabled in the early, post-
hospitalization period. That is, muscle disuse secondary to limited range of motion and muscle 
weakness causes skeletal muscle fiber atrophy and weakness, as well as mitochondrial rarefaction and 
dysfunction that further impair physical fitness. 
Is it FDA approved: (include FDA IDE Number) 
1.  for indication specified? If no, provide justification for proposed use and source of the device. 
Yes. It is approved to mitigate muscle atrophy/dysfunction associated with muscle disuse (501K: 
K093324) (see Appendix 3). 
Risk assessment (non-significant/significant risk) - PI or sponsor needs to assess risk of a device based upon the use of the 
device with human subjects in a research environment.   
The device (and similar devices) has been used extensively in the orthopedic and neural rehabilitation 
settings by physical and occupational therapists and in numerous disease states (heart failure, chronic 
obstructive pulmonary disease, knee replacement) to improve muscle size and function in clinical trial 
settings. Thus, NMES is generally a safe modality, with a long safety record. Although evidence is 
limited, some have suggested that NMES could increase the risk of dislodging a DVT because of the 
rhythmic muscle contractions induced by the electrical stimulation. However, several published reports 
show that NMES significantly reduces the risk of developing DVTs. In fact, the device we are using is 

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FDA-approved for prevention of DVT of the calf muscles immediately following hospitalization, as it 
would function similar to intermittent pneumatic compression. Moreover, we will actively exclude any 
individual with a known coagulopathy or DVT. Because of the location of the stimulating electrodes 
(upper leg), the risk of NMES dislodging a DVT is likely minimal. There are also several case reports 
that NMES may be sensed by cardiac defibrillators as an arrhythmia, causing the device to discharge 
inappropriately. However, interference with ICDs mostly involved low frequency stimulation of the upper 
or lower back. In contrast, a more recent study has shown that higher frequency stimulation of the leg 
muscles does not cause electromagnetic interference with the device (1). Regardless, consistent with 
current clinical practice guidelines (2), we will exclude any volunteers that currently have an implanted 
cardiac defibrillator or pacemaker. Finally, during the first couple of NMES sessions, muscle soreness 
may occur, but this is comparable to what might occur with classical exercise training and dissipates 
over time.  
Literature cited 
1. 
Kamiya, K., Satoh, A., Niwano, S., Tanaka, S., Miida, K., Hamazaki, N., Maekawa, E., Matsuzawa, R., Nozaki, K., 
Masuda, T., and Ako, J. Safety of neuromuscular electrical stimulation in patients implanted with cardioverter 
defibrillators. Journal of Electrocardiology 49, 99-101 
2. 
Houghton, P. E., Nussbaum, E. L., and Hoens, A. M. (2010) Electrophysical agents. Contraindications and 
precautions: an evidence-based approach to clinical decision making in physical therapy. Physiother Can 62, 1-80 
 
SUBJECT CHARACTERISTICS, IDENTIFICATION AND RECRUITMENT  
 
Subject Selection:  Provide rationale for subject selection in terms of the scientific objectives and proposed study design. 
Patients who are hospitalized to the Inpatient Cardiology Service for heart failure with preserved ejection 
fraction (HFpEF) and reduced ejection fraction (HFrEF) otherwise known as diastolic heart failure or 
systolic heart failure will be screened. As the US population ages, there has been a rise in patients 
experiencing HFpEF and HFrEF and, in turn, hospitalizations and readmissions.1-3 Focus has been 
placed on transitional care services for medical and surgical treatments, with little attention on physical 
rehabilitation services, despite the fact that patients prioritize this as an outcome of their treatment and 
that physical disability increases risk of complications and readmission.5-7 After hospitalizationheart 
failure   patients are severely deconditioned.. Our intervention aims to overcome this gap in rehabilitative 
care early after hospital discharge to improve functional recovery 
1. 
Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 
2017;14(10):591-602. 
2. 
Bello NA, Claggett B, Desai AS, et al. Influence of previous heart failure hospitalization on cardiovascular events in 
patients with reduced and preserved ejection fraction. Circ Heart Fail. 2014;7(4):590-595. 
doi:10.1161/CIRCHEARTFAILURE.113.001281 
3. 
Nichols GA, Reynolds K, Kimes TM, Rosales AG, Chan WW. Comparison of Risk of Re-hospitalization, All-Cause 
Mortality, and Medical Care Resource Utilization in Patients With Heart Failure and Preserved Versus Reduced 
Ejection Fraction. Am J Cardiol. 2015;116(7):1088-1092. 
4. 
Aggarwal M, Bozkurt B, Panjrath G, Aggarwal B, Ostfeld RJ, Barnard ND, Gaggin H, Freeman AM, Allen K, Madan S, 
Massera D, Litwin SE; American College of Cardiology’s Nutrition and Lifestyle Committee of the Prevention of 
Cardiovascular Disease Council. Lifestyle Modifications for Preventing and Treating Heart Failure. J Am Coll Cardiol. 
2018 Nov 6;72(19):2391-2405 
5. 
Reeves GR, Whellan DJ, Duncan P, et al. Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) 
trial: Design and rationale. Am Heart J. 2017;185:130-139 
6. 
Fisher SR, Kuo YF, Sharma G, et al. Mobility after hospital discharge as a marker for 30-day readmission. J Gerontol 
A Biol Sci Med Sci. 2013;68(7):805-810 
7. Reeves GR, Whellan DJ, Patel MJ, et al. Comparison of Frequency of Frailty and Severely Impaired Physical Function 
in Patients ≥60 Years Hospitalized With Acute Decompensated Heart Failure Versus Chronic Stable Heart Failure 
With Reduced and Preserved Left Ventricular Ejection Fraction. Am J Cardiol. 2016;117(12):1953-1958 
Vulnerable Populations:  Explain the rationale for involvement of special classes of subjects, if any.  Discuss what procedures 
or practices will be used in the protocol to minimize their susceptibility to undue influences and unnecessary risk (physical, 
psychological, etc.).  
X 
Not applicable 
 
 
Number of Subjects:  What is the anticipated number of subjects to be enrolled at UVM/UVM Medical Center and in the case 
of a multi-center study, with UVM/UVM Medical Center as the lead, the total number of subjects for the entire study. 

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The proposed sample of 60 participants is based on having sufficient power to calculate differences in 
our primary outcome (6MW) between the control condition and the intervention and accommodating for 
potential drop outs (20%) from the study. We will need to recruit 60 patients with our target of 48 
patients to complete the study  
Inclusion/Exclusion Criteria:  Eligibility and ineligibility criteria should be specific. Describe how eligibility will be determined 
and by whom.  Changes to the eligibility criteria at a later phase of the research have the potential to invalidate the research. 
Inclusion/Exclusion Criteria: Patients will be recruited if they: 1) have clinical diagnosis of heart failure 
being actively managed during hospitalization, 2) live within 30 miles of UVMMC and are between 50-90 
years of age. Patients will be excluded if they have: 1) severe dementia/alzheimer’s disease 2)an active 
malignancy, excluding non-melanoma skin cancer or low-grade prostate cancer under active 
surveillance; 3) exercise-limiting vascular or neuromuscular disease; 4) body mass index ≥40 kg/m2 or 
5*) an existing or history of deep vein thrombosis (DVT) or have an implantable cardioverter-defibrillator 
(ICD) or pacemaker (PPM).1 *The last criteria is a contraindication for NMES and we will withdraw 
patients if they have an existing or history of deep vein thrombosis of the lower extremities or have an 
ICD or PPM 
 
Literature cited: 
1. 
Houghton, P. E., Nussbaum, E. L., and Hoens, A. M. (2010) Electrophysical agents. Contraindications and 
precautions: an evidence-based approach to clinical decision making in physical therapy. Physiother Can 62, 1-80 
Inclusion of Minorities and Women:  Describe efforts to include minorities and women.  If either minorities or women are 
excluded, include a justification for the exclusion.  
Inclusion of Women 
     This study will include equal numbers of men and women. 
Inclusion of Minorities 
     Every effort will be made to recruit minorities for the proposed studies. The contribution of minorities 
to the total population of Vermont is 3.2%, with a similar minority profile in Chittenden County (3.6%), 
where the University of Vermont (UVM) is located.  
Inclusion of Children: Describe efforts to include children.  Inclusion is required unless a clear and compelling rationale shows 
that inclusion is inappropriate with respect to the health of the subjects or that inclusion is inappropriate for the purpose of the 
study.  If children are included, the description of the plan should include a rationale for selecting or excluding a specific age 
range of children.  When included, the plan must also describe the expertise of the investigative team in working with children, 
the appropriateness of the available facilities to accommodate children, and the inclusion of a sufficient number of children to 
contribute to a meaningful analysis relative to the purpose of the study.  If children are excluded then provide appropriate 
justification. Provide target accrual for this population. 
The proposed studies will not include children because HFpEF/HFrEF is confined to the adult/ older 
adult population. 
For protocols including the use of an investigational drug, indicate whether women of childbearing potential have been included 
and, if not, include appropriate justification. 
Not applicable 
If HIV testing is included specifically for research purposes explain how the test results will be protected against unauthorized 
disclosure.  Include if the subjects are to be informed of the test results.  If yes, include the process and provision for 
counseling.  If no, a rationale for not informing the subjects should be included.   
X 
Not applicable 
 
 
Recruitment:  Describe plans for identifying and recruitment of subjects.  All recruitment materials (flyers, ads, letters, etc) 
need to be IRB approved prior to use.   
Patients will be recruited from the Inpatient Cardiology Service on Miller. 
 
 
FINANCIAL CONSIDERATIONS  
 
Expense to Subject:  If the investigation involves the possibility of added expense to the subject (longer hospitalization, extra 
studies, etc.) indicate in detail how this will be handled. In cases where the FDA has authorized the drug or device company to 

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charge the patient for the experimental drug or device, a copy of the authorization letter from the FDA or sponsor must 
accompany the application. Final approval will not be granted until the IRB receives this documentation. 
There are very limited circumstances under which study participants may be responsible (either directly or via their insurance) 
for covering some study-related expenses. If the study participant or their insurer(s) will be billed for any portion of the research 
study, provide a justification as to why this is appropriate and acceptable. For example, if the study involves treatment that is 
documented standard of care and not investigational, state so. In these cases, the protocol and the consent should clearly 
define what is standard of care and what is research. 
The only added cost to the volunteer is for their transportation to and from the research center for 
additional testing associated with these studies, as described above. 
Payment for participation:  Describe all plans to pay subjects, either in cash, a gift or gift certificate. Please note that all 
payments must be prorated throughout the life of the study. The IRB will not approve a study where there is only a lump sum 
payment at the end of the study because this can be considered coercive. The amount of payment must be justified. Clarify if 
subjects will be reimbursed for travel or other expenses. 
 
Not applicable 
 
We propose to compensate volunteers $200 for their participation. If volunteers do not complete the 
study, their compensation will be prorated accordingly.  
At Initial Evaluation:  
$50 
Week 1 f/u phone call:  
$25 
Week 2 f/u phone call:  
$25 
Week 3 f/u phone call:  
$25 
Week 4 f/u phone call:  
$25 
Final evaluation:  
 
$50 
 
 
Collaborating Sites.  When research involving human subjects will take place at collaborating sites or other performance sites 
when UVM/UVM Medical Center is the lead site, the principal investigator must provide in this section a list of the collaborating 
sites and their Federal-wide Assurance numbers when applicable.  (agreements may be necessary) 
X 
Not applicable 
 
 
 
 
 
INFORMED CONSENT  
 
Consent Procedures:  Describe the consent procedures to be followed, including the circumstances under which consent will 
be obtained, who will seek it, and the methods of documenting consent.  Specify the form(s) that will be used e.g. consent (if 
multiple forms explain and place identifier on each form), assent form and/or HIPAA authorization (if PHI is included).  These 
form(s) must accompany the protocol as an appendix or attachment.   
 
Note:  Only those individuals authorized to solicit consent may sign the consent form confirming that the prospective subject was 
provided the necessary information and that any questions asked were answered. 
If the patient expresses interest in the study and would like more information about the study, the 
research coordinator or PI will contact the volunteer, explain the study and will provide a copy of the 
informed consent. The PI and/or the research coordinator will answer any questions by phone or in 
person. Moreover, the PI or the research coordinator will discuss the protocol with the volunteer at length 
and answer any remaining questions. 
Information Withheld From Subjects:  Will any information about the research purpose and design be withheld from potential 
or participating subjects?  If so, explain and justify the non-disclosure and describe plans for post-study debriefing.   
X 
Not applicable 
 
 
 
Attach full grant application, including budget information and/or any contract or draft contract 
associated with this application.