Community Ambulation Project (CAP) Ancillary Study - PUSH Plus Protein Pilot Study
Phase: NA
Conditions: Hip Fracture
Sponsor: University of Maryland, Baltimore

                                    
PUSH PLUS PROTEIN PILOT STUDY FOR HIP FRACTURE PATIENTS 
PROTOCOL (Version 3.0) 
 
 
Summary of Modifications to Protocol Version 2.0 for Version 3.0 
 
Summary of Modifications to Protocol Version 1.0 for Version 2.0 
 
 
 
 
Version 
(date) 
Section 
Brief Summary of Modification 
9-5-2018 
10.1 and 10.2 
We removed the Biodex ankle plantarflexion-dorsiflexion measurement 
from the baseline and 16-week follow-up assessments. We will test Biodex 
knee flexion/extension only, which is the best representative marker for 
torque/ power production and importantly related to gait and mobility 
function.  The Biodex ankle test is less reliable and the knee test a better 
performance predictor. When investigators looked at data from the CAP-MP 
companion study, they learned that many in this functionally very 
challenged cohort could not achieve the 60 deg/sec needed to perform the 
ankle test; thus, the torque/power was not calculated, as there was more 
missing data for the Biodex ankle test than for the Biodex knee test which 
was more complete. The ankle test for the selected contraction velocity is 
more difficult for many in this study population to achieve in order to 
capture valid measurement. Therefore, experts in the Department of Physical 
Therapy and Rehabilitation Science (PTRS) suggest using the Biodex knee 
test only for the current pilot study because it more accurately represents the 
entire subject cohort being tested. Participants will be able to correctly 
perform the knee test which was not true for the ankle test in the companion 
study. 
 
10.1 and 10.2 
We added the Four-Square Step Test (FSST) to be done at the baseline and 
16-week follow-up visits as a dynamic balance assessment. 
Version 
(date) 
Section 
Brief Summary of Modification 
7-24-2018 
All sections 
Changed study clinician to study physician 
 
12.5 and  Figures 5b-d 
Modified procedures for reportable adverse events to coincide with reporting 
procedures outlined by NIA and the Pepper Center OAIC. 
 
7.5 
Modified recruitment procedures to describe how patients will be contacted 
after discharge from the hospital and how potential participants who contact 
the study office will undergo a brief pre-screening to assess eligibility.  
 
17 
Modified the publication policy to state that publications will be overseen by 
study leadership and added a note that final papers using CAP or CAP-MP 
data may need to be reviewed by the CAP PASC. 

 
 
 
 
PUSH Plus Protein Pilot Study for Hip Fracture Patients 
 
Principal Investigator: 
 
Denise Orwig, PhD 
 
 
Supported by: 
 
The National Institute on Aging 
R37 AG009901(PI: J. Magaziner) 
 
 
Trial Registration 
ClinicalTrials.gov 
NCT03410823  
Initial release: 12/07/2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Version 3.0 
September 5, 2018 
 

PUSH Plus Protein Pilot Protocol version3.0 
 
ii 
Table of Contents 
 
Section 1: Executive Summary ...................................................................................... 2 
Section 2: Clinical Site.................................................................................................... 5 
Section 3: Study Organization ........................................................................................ 6 
3.1 Study Administration ............................................................................................. 6 
3.1.1 Study Chair .................................................................................................... 6 
3.1.2 National Institute on Aging (NIA) ................................................................... 6 
3.1.3 Data and Safety Monitoring Board (DSMB) ................................................... 6 
3.1.4 Investigative Team ........................................................................................ 6 
3.1.5 UMB Investigational Drug Services (IDS) ...................................................... 7 
3.1.6 University of Maryland General Clinical Research Center (GCRC) ............... 7 
3.1.7 Study Clinical Site ......................................................................................... 7 
Section 4: Study Objectives ........................................................................................... 8 
4.1 Primary Objective ................................................................................................. 8 
4.2 Secondary Objectives ........................................................................................... 8 
Section 5: Background ................................................................................................... 8 
5.1 Residual Deficits in Precursors of Community Ambulation ................................... 8 
5.2 Exercise Studies in Persons after Hip Fracture .................................................. 10 
5.3 Rationale for the Interventions ............................................................................ 11 
5.4 Primary Outcome Measure ................................................................................. 12 
Section 6: Study Design ............................................................................................... 13 
6.1 Overview of Study Design .................................................................................. 13 
6.2 Interventions ....................................................................................................... 14 
Section 7: Selection and Enrollment of Participants ..................................................... 14 
7.1 Eligibility ............................................................................................................. 14 
7.1.1 Required Baseline Data .............................................................................. 15 
7.2 Inclusion Criteria (Target Population) ................................................................. 16 
7.3 Exclusion Criteria ................................................................................................ 16 
7.4 Identification of Hip Fracture Patients ................................................................. 17 
7.5 Informed Consent ............................................................................................... 17 
7.5.1 Enrollment ................................................................................................... 18 
7.6 Monitoring Recruitment and Retention ............................................................... 18 
Section 8: Study Interventions ...................................................................................... 19 
8.1 Overview ............................................................................................................ 19 
8.2 Nutritional Support .............................................................................................. 19 
8.3 PUSH Intervention .............................................................................................. 20 
8.4 Protein Supplement ............................................................................................ 22 
8.5 Treatment Fidelity Plan ....................................................................................... 22 
8.5.1 Initial Training for Procedural Reliability ...................................................... 22 
8.5.2 Ensuring Ongoing Competency ................................................................... 22 
8.6 Scheduling Intervention Visits............................................................................. 23 
Section 9: Study Measures .......................................................................................... 23 
9.1 Screening Evaluations ........................................................................................ 24 
9.1.1 Modified Mini-Mental State Examination (3MS) ........................................... 24 
9.2 Primary Outcome Measure: Community Ambulation .......................................... 24 
9.3 Secondary Outcome Measures .......................................................................... 24 
9.3.1 Cognitive Function (3MS) ............................................................................ 24 
9.3.2 Short Physical Performance Battery (SPPB) ............................................... 24 
9.3.3 Activities of Daily Living (ADLs) ................................................................... 25 

PUSH Plus Protein Pilot Protocol version3.0 
 
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9.3.4 Quality of Life (SF-36) ................................................................................. 26 
9.3.5 Nutritional Status ......................................................................................... 26 
9.3.6 Muscle and Fat Mass .................................................................................. 26 
9.3.7 Muscle Composition: Intramuscular fat and muscle volume ........................ 26 
9.3.8 Strength ....................................................................................................... 26 
9.3.9 Power .......................................................................................................... 26 
9.3.10 
Bone Mineral Density ............................................................................... 26 
9.3.11 
Gait and Balance (GAITrite) ..................................................................... 27 
9.3.12 
Bone Turnover Markers ........................................................................... 27 
9.3.13 
Hormones ................................................................................................ 27 
9.3.14 
Inflammatory Cytokines ........................................................................... 27 
9.3.15 
Cognitive Function (Trail Making Test (Trails A and B))........................... 27 
9.3.16 
Waist Circumference................................................................................ 27 
9.4 Improvement in Walking ..................................................................................... 27 
9.5 Clinical and Background Characteristics ............................................................ 27 
9.5.1 Demographic and Surgical Characteristics.................................................. 27 
9.5.2 Functional Comorbidity Index ...................................................................... 27 
9.5.3 Weight, Height, and BMI.............................................................................. 28 
9.6 Other Measures to be Monitored ........................................................................ 28 
9.6.1 Adherence ................................................................................................... 28 
9.6.2 Weight Loss ................................................................................................. 28 
9.6.3 Reportable Adverse Events (RAEs) ............................................................ 28 
9.6.4 Expected Adverse Events (AEs) ................................................................. 28 
Section 10: 
Study Procedures ................................................................................. 29 
10.1 Baseline Assessments ....................................................................................... 29 
10.2 Follow-up Assessment ....................................................................................... 29 
10.3 Telephone Interviews ......................................................................................... 30 
10.4 Timing of Study Procedures ............................................................................... 30 
Section 11: 
Safety Assessments ............................................................................. 31 
11.1 Participant Safety Parameters: Methods and Timing .......................................... 31 
11.1.1 
Pre-Intervention Safety Screening ........................................................... 31 
11.1.2 
Safety Considerations for Study Assessments ........................................ 31 
11.1.3 
Safety Considerations for the PUSH Intervention .................................... 32 
11.1.4 
Safety Measures during the PUSH Intervention ...................................... 33 
11.1.5 
Safety Considerations for the Protein Intervention ................................... 33 
11.1.6 
Safety Measures for the Protein Intervention ........................................... 35 
11.1.7 
Safety Considerations for Nutritional Support .......................................... 35 
11.1.8 
Safety Measures for Nutritional Support .................................................. 36 
11.2 Confidentiality ..................................................................................................... 36 
11.3 Participant Education about Potential Risks ....................................................... 36 
Section 12: 
Reportable Adverse Events (RAEs) and Expected AEs ....................... 36 
12.1 Overview ............................................................................................................ 36 
12.2 Classifying Adverse Events ................................................................................ 37 
12.2.1 
Severity .................................................................................................... 37 
12.2.2 
Expectedness .......................................................................................... 37 
12.2.3 
Relatedness ............................................................................................. 38 
12.3 Expected AEs ..................................................................................................... 38 
12.4 Reportable AEs .................................................................................................. 38 
12.4.1 
Serious Adverse Event (SAE) .................................................................. 39 
12.4.2 
Unexpected Adverse Event ..................................................................... 39 

PUSH Plus Protein Pilot Protocol version3.0 
 
iv 
12.4.3 
Injury that Occurs while Under the Supervision of Study Related 
Personnel ............................................................................................................... 39 
12.5 Expected AE and RAE Collection and Reporting ............................................... 40 
12.6 Evaluation and Follow-up of RAEs ..................................................................... 44 
12.6.1 
Action Taken ............................................................................................ 44 
12.7 Responsibilities ................................................................................................... 45 
12.7.1 
Study Physician ....................................................................................... 45 
12.7.2 
Independent Safety Monitor (ISM) ........................................................... 45 
12.8 Reporting Expected AEs and RAEs to the DSMB .............................................. 45 
Section 13: 
Intervention Discontinuation ................................................................. 46 
Section 14: 
Data Analyses ...................................................................................... 46 
14.1 Primary Aim ........................................................................................................ 46 
14.2 Secondary Objectives ......................................................................................... 46 
14.3 Missing Data ....................................................................................................... 47 
14.4 Sample Size Adequacy ...................................................................................... 47 
Section 15: 
Data Capture, Data Management, and Quality Assurance .................. 47 
15.1 Data Management .............................................................................................. 47 
15.1.1 
Processing of Paper Data Forms ............................................................. 47 
15.1.2 
Reportable Adverse Events Coding ......................................................... 47 
15.1.3 
Extraction of Data for Analysis and Reporting ......................................... 48 
15.2 Protection of Data ............................................................................................... 48 
15.2.1 
Physical Security and Backup .................................................................. 48 
15.3 Study Management Database ............................................................................ 48 
15.4 Quality Assurance (QA) ...................................................................................... 48 
15.4.1 
Training .................................................................................................... 48 
15.4.2 
Protocol Deviations .................................................................................. 49 
Section 16: 
Participant Rights and Confidentiality ................................................... 49 
16.1 Institutional Review Board (IRB) ......................................................................... 49 
16.2 Informed Consent Forms (ICF) ........................................................................... 49 
16.2.1 
Disposition of Informed Consent Forms ................................................... 50 
16.2.2 
HIPAA Authorization ................................................................................ 50 
16.3 Participant Confidentiality ................................................................................... 50 
Section 17: 
Research Publication Policy ................................................................. 51 
17.1 Concurrent Studies ............................................................................................. 51 
Section 18: 
Study Team Roster .............................................................................. 52 
Section 19: 
References ........................................................................................... 54 
 
 
 
 

PUSH Plus Protein Pilot Protocol version3.0 
 
v 
List of Tables 
 
Table 
Title 
Section 
Table 1 Timing of Study Procedures 
10.4 
Table 2 Safety Alerts and Actions for Study Assessments 
11.1.2 
Table 3 Safety Alerts and Actions for Interventions 
11.1.5 
 
 
List of Figures 
 
Figure 
Title 
Section 
Figure 1 
Timeline for Recruitment and Follow-up 
6.1 
Figure 2 
Algorithm for Screening 
7.1 
Figure 3 
Shuttle Device  
8.3 
Figure 4 
Classification and Analysis of Primary Outcome 
11.5 
Figure 5a 
Collection and Reporting Process for Expected AEs 
13.5 
Figure 5b 
Collection and Reporting Process for RAEs Collected During 
Standardized Telephone Interviews 
13.5 
Figure 5c 
Collection and Reporting Process for RAEs Identified Anytime Other 
than During a Standardized Telephone Interview 
13.5 
Figure 5d 
Reporting Process for RAEs 
13.6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
PUSH Plus Protein Pilot Protocol version3.0 
 
vi 
List of Abbreviations 
 
 
Term 
Abbr. 
Active range of motion 
AROM 
Activities of daily living 
ADL 
Adverse event 
AE 
Arthrogenic muscle response 
AMR 
Baltimore Hip Studies 
BHS 
Body mass index 
BMI 
Cardiopulmonary resuscitation 
CPR 
Center for Medicare and Medicaid 
Services 
CMS 
Data and Safety Monitoring Board 
DSMB 
Data Management Plan 
DMP 
Diastolic blood pressure 
DBP 
Eight-repetition maximum 
8-RM 
Emergency Medical Service 
EMS 
Functional Comorbidity Index 
FCI 
Generalized estimating equations 
GEE 
Health Insurance Portability and 
Accountability Act 
HIPAA 
Heart rate 
HR 
Heart rate reserve 
HRR 
Heating, ventilation and air conditioning 
HVAC 
Incremental net benefits 
INB 
Independent Safety Monitor 
ISM 
Information Technology 
IT 
Informed Consent Form 
ICF 
Institutional Review Board 
IRB 
Investigational Drug Services 
IDS 
Intervention Monitor 
IM 
Manual of Procedures 
MOP 
Term 
Abbr. 
Mini Nutritional Assessment-Short Form 
MNA®-SF 
Modified Mini-Mental State examination 
3MS 
National Institute on Aging 
NIA 
National Institutes of Health 
NIH 
Peak oxygen uptake 
VO2peak 
Pepper Assessment Tool for Disability 
PAT-D 
Physical therapist 
PT 
Primary care provider 
PCP 
Principal investigator 
PI 
Protected Health Information 
PHI 
Publications and Ancillary Studies 
Committee 
PASC 
Quality assurance 
QA 
Quality control 
QC 
Rating of perceived exertion 
RPE 
Redundant Array of Independent Risks 
RAID 
Registered dietician 
RD 
Reportable Adverse Event 
RAE 
Resource-Based Relative Value Scale 
RBRVS 
Serious adverse event 
SAE 
Short Physical Performance Battery 
SPPB 
Six-Minute Walk Test 
SMWT 
Skilled nursing facility 
SNF 
Spine Patient Outcomes Research Trial 
SPORT 
Standard Operating Procedure 
SOP 
Statistical Analysis Software 
SAS 
Systolic blood pressure 
SBP 
University of Maryland Baltimore 
UMB 
Weighted estimating equations 
WEE 
 
 

PUSH Plus Protein Pilot Protocol version3.0 
 
2 
Section 1: Executive Summary 
 
Hip fracture is a common problem among older individuals. This year in the United States 
approximately 260,000 people aged 65 and older will break a hip. The goal of current standard 
of care after hip fracture is to achieve independent, household ambulation 2-3 months after 
surgery, yet decreased functional ability typically persists well beyond three months and many 
patients never resume independent ambulation outside the home.  Previous research has 
established that one must be able to walk at least 300 meters (~330 yards) within 6 minutes to 
re-establish routine interactions in the community, such as going to the store or to church. In 
part, this is based on the average distance from handicapped parking spaces into most facilities. 
Activity and exercise are believed to be of benefit for reducing disability in older adults, yet the 
majority of older adults does not participate in regular exercise and is not active. This is 
especially true for older adults following hip fracture after they complete the usual rehabilitation 
program.  
 
This research study is being done to test a 16-week, multi-part exercise intervention for hip 
fracture patients that will be supervised by specially trained physical therapists (PTs). The 
exercise intervention uses a novel machine to provide strength and endurance training in the 
home. This has been shown in smaller studies to be safe and effective at increasing strength. 
We want to test whether adding a protein supplement to the exercise intervention leads to more 
improvements in a person’s ability to walk in their own home and in the local community. With 
this knowledge, we hope to help a greater number of hip fracture patients enjoy a more 
complete recovery and improved overall health. 
 
The research is based on the premise that successful community ambulation requires certain 
factors that are influenced by underlying physical or chemical processes. The key factors 
include endurance, walking speed, muscle strength, balance, lower extremity function, skeletal 
integrity, and fracture healing. We believe that physical activity and protein supplementation can 
impact these factors to improve the ability to walk. We want to gain a better understanding of 
which factors play a role by performing tests that measure physical function, strength, balance, 
level of inflammation, bone turnover rate, muscle density, and body composition. 
 
Participant data from this pilot study will be compared to data from participants who received the 
PUSH intervention without protein in two recently completed studies: 1) Community Ambulation 
Project (CAP parent study) and 2) Community Ambulation Project- Mechanistic Pathways (CAP-
MP ancillary study). 
 
Study Title 
PUSH Plus Protein Pilot Study for Hip Fracture Patients (hereafter referred to as PUSH Plus 
Protein) 
 
Objectives 
The primary outcome will be to test whether the PUSH Plus Protein intervention improves 
community ambulation (as measured by distance walked in six minutes) compared to PUSH 
intervention alone (from CAP study) at the end of 16 weeks.  The effects of PUSH Plus Protein 
on precursors to community ambulation compared to the PUSH intervention alone (CAP study) 
and the effects of PUSH Plus Protein intervention on the mechanistic factors compared to 
PUSH intervention alone (from CAP-MP study) will also be examined. In addition, the safety and 
tolerability of delivering the PUSH Plus Protein intervention to hip fracture patients will be 
assessed.  

PUSH Plus Protein Pilot Protocol version3.0 
 
3 
 
Design and Outcomes 
In addition to providing important information on adherence, feasibility, and safety, this pilot 
study of 30 hip fracture patients has the unique advantage of being able to compare data to two 
recently completed studies where participants received the PUSH intervention without protein 
supplementation described below. 
 
Participants in this pilot will receive the same specific multi-component 16-week intervention, 
PUSH, as participants in the multi-site CAP randomized controlled trial. The PUSH intervention 
uses a novel machine to provide strength and endurance training in the home. The purpose of 
this pilot study is to test whether adding a protein supplement to the PUSH intervention leads to 
greater improvement in a person’s functional ability compared to the PUSH intervention alone; 
therefore, data in this pilot study will be compared to data from participants in the CAP study 
across the three clinical sites who received the PUSH intervention alone (n=105). Our working 
hypothesis is that PUSH Plus Protein will lead to greater improvements in ability to walk in the 
community compared to PUSH measured using the distance walked in six minutes (SMWT). 
 
We will also compare the effect of PUSH Plus Protein intervention to PUSH intervention alone 
on secondary outcomes in the CAP study believed to be precursors to community ambulation 
including activities of daily living (ADLs), quality of life, lower extremity physical performance, 
increase of ≥ 50 meters in distance walked in six minutes, cognitive status, and nutritional 
status. 
 
We can also compare participants in the pilot study to participants who received PUSH alone in 
the CAP-MP study (HP-53145) (n=19) to examine whether PUSH Plus 
Protein has an impact on the mechanistic factors on the pathway to recovery of ambulatory 
ability after hip fracture. We will assess whether, at the end of the 16 week intervention, 
participants in the PUSH Plus Protein intervention, compared to PUSH alone, have: a) greater 
muscle volume and attenuation (i.e., reduced intra-muscular fat) of the thigh; b) greater lower 
extremity strength; c) better gait parameters; d) greater bone mineral density and bone strength; 
e) more bone formation and less bone resorption; and f) lower levels of circulating inflammatory 
cytokines. 
 
The pilot study will provide important information related to the safety and tolerability of 
delivering the PUSH Plus Protein intervention to hip fracture patients.  We will also be able to 
estimate the sample size requirements for a more definitive study. 
 
Study activities for participants meeting eligibility criteria will take place after post-acute 
rehabilitation ends, up to 26 weeks after admission to the hospital for hip fracture. Patients age 
60 and older who have had surgical repair for hip fracture will be identified in study hospitals or 
by self-referral and evaluated for eligibility. Following consent to participate, eligible participants 
will undergo a comprehensive baseline assessment. Participants completing the required 
measures of the baseline assessment will be eligible to receive the intervention.  All participants 
will receive the PUSH Plus Protein intervention.  The follow-up assessment will occur after the 
intervention is completed, approximately 16 weeks after baseline testing.   
 
Interventions and Duration 
All participants will receive the PUSH Plus Protein intervention. Within a week of completing 
baseline testing, the study physical therapist (PT) will initiate the exercise intervention and the 
protein supplement in the home setting. Participants will receive two physical therapy visits a 
week for 16 weeks, on non-consecutive days, for a total of 32 visits. Each visit will last 

PUSH Plus Protein Pilot Protocol version3.0 
 
4 
approximately 60 minutes. Visits will take place in the participant’s place of residence. At the 
same time, participants will receive a daily whey-based protein powder supplement containing 
27.6g of protein. Participants will also receive 2,000 IU of vitamin D3, 600 mg of calcium, and a 
multivitamin daily during the 16-week study period and counseling with a registered dietician to 
ensure body weight stability and adequate nutrient intake inclusive of a healthy diet. 
 
PUSH Exercise Intervention 
The PUSH exercise intervention is based on improving specific precursors to community 
ambulation. The intervention addresses endurance with continuous upright exercise for 20 
minutes; function by improving fast walking needed to navigate streets outdoors, standing from 
a chair, and stair negotiation; muscle performance by exercising to enhance lower extremity 
strength in functionally relevant muscles moving through locomotion-appropriate movements 
and ranges; and balance by performing unilateral activities and activities with decreased base of 
support. The components of exercise are woven together into one program that minimizes 
participant burden. Participants will be instructed to complete the endurance component 
independently one to two times/week by walking for a similar duration and intensity as they have 
been doing with the PT during the supervised visits.  
 
The strength components of the muscle performance intervention will be performed using a 
portable progressive resistive exercise device (Shuttle® MiniPress, Contemporary Design 
Company, P.O. Box 5089, Glacier, WA 98244). Muscle performance will focus on bilateral hip 
extensors, hip abductors, knee extensors, and plantar flexors because of their role in function, 
specifically gait and transfer activities. Balance and strength will be addressed with additional 
exercises performed while standing. The endurance intervention will begin initially with two to 
three minutes of continuous upper and lower extremity active range of motion (AROM) with the 
participant sitting. These exercises are intended to increase the participants’ heart rate (HR) or 
exertion closer to the target zone. The participant will then be asked to walk on level surfaces 
and up and down a single or multiple steps, if able and available, to keep the HR within the 
training zone for 20 minutes. The PT may also engage the participant in additional exercises 
such as upper and lower extremity AROM exercises to keep the HR elevated. 
 
As a measure of treatment fidelity, we will monitor physiologic response (heart rate) during the 
intervention sessions by measuring heart rate. Heart rate monitoring will provide a dichotomous 
variable reflecting whether, during each segment of the intervention session, the participant’s 
average HR was equal to or greater than his or her target heart rate (±5 beats). 
 
Protein Supplement 
Participants will receive a whey-based protein powder supplement containing 27.6g of protein. 
This dose induces maximum muscle protein synthesis post-exercise. Participants will mix the 
supplement in 8 oz. of water (or other beverage) or soft food (e.g., yogurt, soup) and consume 
immediately following each exercise session with the study PT. On days when they do not have 
a physical therapy visit with the study PT, participants will be instructed to take the supplement 
at the meal time closest to the time of scheduled PT visits to maintain regular daily dosing 
schedule. 
 
Nutrition Intervention 
Given the importance of maintaining nutrition in older adults after an acute event, we will provide 
all participants with 2000 IU vitamin D3, 600 mg of calcium, and a multivitamin daily for the 
duration of the 16-week study. Nutritional counseling will also be provided to ensure weight 
stability, adequate nutrient intake of 1.2-1.5 g protein/kg body weight inclusive of a healthy diet 
(50% carbohydrate, 20% protein, 30% fat). Participants will be screened at the time of baseline 

PUSH Plus Protein Pilot Protocol version3.0 
 
5 
testing to assess nutritional risk using the Mini Nutritional Assessment-Short Form (MNA®-SF). 
Those who score ≤7 (malnourished) on the MNA®-SF at baseline and participants with serum 
albumin 2.5-3.5 g/dl (regardless of the score on MNA®-SF) will receive a visit from a registered 
dietician (RD) in their place of residence within seven days of baseline testing. The RD will 
evaluate and counsel them on making dietary modifications based on their protein, caloric and 
other dietary deficiencies using a standardized approach across the three study sites. The RD 
will follow up with participants by telephone one week after the visit to assess understanding 
and implementation of recommendations. Participants who score 8-11 (at risk of malnutrition) on 
MNA®-SF at baseline and have serum albumin level >3.5 g/dl will receive a telephone dietary 
consultation with the RD within seven days of baseline testing. Based on the participant's eating 
habits and food intake, the RD may make the clinical determination that an in-person 
consultation is warranted. In these cases, the RD will schedule an in-person dietary 
consultation, following the same protocol as those who score in the malnourished range. Those 
screening in the normal range (with a score ≥12 on the MNA®-SF) at baseline and who have 
serum albumin level >3.5 g/dl will receive brief telephone contact within seven days of baseline 
testing from the RD to discuss the importance of calorie and protein intake. Weight will be 
monitored during home PT visits every four weeks and those who lose 2% or more body weight 
in a four-week period will receive another telephone consultation by the study RD. This protocol 
applies to anyone who loses 2% or more of body weight, regardless of whether the participant is 
trying to lose weight. In the event that a weight measurement is not obtained at the last PT visit, 
the participant’s weight at the 16-week follow-up assessment will be compared to his or her 
baseline weight and, if there is weight loss of 5% or more, the study physician will review the 
participant’s weight trajectory, baseline BMI, baseline MNA®-SF score, and registered 
dietician’s documentation and, if warranted based on clinical judgment, will refer the participant 
to a dietician or medical provider for follow-up of possible poor nutritional status. 
 
Sample Size and Population 
The target sample size for this pilot study is 30 hip fracture patients who will receive the PUSH 
Plus Protein intervention.  Study inclusion criteria are: 1) Closed, non-pathologic, minimal 
trauma hip fracture with surgical fixation; 2) Age 60 or older at time of baseline testing; 3) Living 
in the community at time of fracture and at time of baseline testing; and 4) Ambulating without 
human assistance during the two months prior to fracture.  Participants for whom it is not safe to 
participate in the intervention will be excluded, as will those who are very unlikely to benefit and 
in whom the intervention is not feasible. 
 
Section 2: Clinical Site 
 
University of Maryland Baltimore  
Denise Orwig, PhD 
Principal Investigator 
660 W. Redwood Street, Suite 200 
Baltimore, MD 21201  
Phone: 410-706-2406  
Fax:     410-706-4433  
dorwig@som.umaryland.edu  
 
 
 

PUSH Plus Protein Pilot Protocol version3.0 
 
6 
Section 3: Study Organization 
The PUSH Plus Protein Pilot study is a single-site study conducted at the University of Maryland 
Baltimore. In addition to the Department of Epidemiology and Public Health (EPH) where the PI 
has a faculty appointment, the project will utilize resources provided by the Department of 
Physical Therapy and Rehabilitation Science (PTRS), University of Maryland General Clinical 
Research Center (GCRC), University of Maryland Investigational Drug Service (IDS), Baltimore 
Veteran’s Affairs Maryland Health Care System (VAMHCS), and the University of Maryland 
Claude D. Pepper Older American Independence Center (UM-OAIC) Data and Safety 
Monitoring Board (DSMB). Please see Section 18: for a complete Study Team Roster. 
 
3.1 Study Administration 
 
3.1.1 Study Chair  
The principal investigator (PI) of the grant awarded by the National Institute on Aging (NIA) will 
serve as the study chair.  Responsibilities of the study chair will include:  
• 
Providing overall organization and scientific direction of the trial 
• 
Administering logistics for the Data and Safety Monitoring Board (DSMB) in consultation 
with the NIA program official 
• 
Providing updates on progress to the NIA 
• 
Defining analyses of study data 
• 
Overseeing manuscript preparation 
 
3.1.2 National Institute on Aging (NIA) 
This is an investigator-initiated project and funding is provided by a MERIT Award.  The funding 
agency is the NIA. The PI will report study progress to the NIA on an annual basis unless asked 
to report at a different interval.  According to PA-10-067, a Non-Competing Continuation Grant 
Progress Report (PHS 2590) will be completed by the PI annually and financial statements 
will be provided as required in the NIH Grants Policy Statement.  A final progress report, 
invention statement, and Financial Status Report will be submitted by the PI when the award 
is relinquished or when it is terminated. 
 
3.1.3 Data and Safety Monitoring Board (DSMB)   
The UM-OAIC DSMB reviews all reported adverse events (AEs), serious adverse events 
(SAEs), and unanticipated problems, and compliance in accordance with NIH/NIA and local 
UMB IRB guidance/polices. AEs, SAEs and unanticipated problems will be reported to the UM-
OAIC center director, UMB IRB, and NIH/NIA. The DSMB will base decisions regarding 
continuation, modification, or termination on the study's ability to recruit subjects, patient 
safety/risk changes, audit findings, and study non-compliance to adhere to protocol. The DSMB 
will discharge itself from its duties when the study is complete.  
 
 
3.1.4 Investigative Team 
The Investigative Team will be charged with the overall governance of study conduct.  
Responsibilities will include:  
• 
Approving the final protocol and manual of operations 
• 
Supervising the overall execution of the trial 
• 
Generating and approving study policies 
• 
Considering modifications of the protocol and study operations 
• 
Reviewing issues related to protocol deviations  
• 
Implementing recommendations of the DSMB 

PUSH Plus Protein Pilot Protocol version3.0 
 
7 
 
All major scientific decisions will be determined by simple majority vote of the members of the 
Investigative Team.  If there is a tie or if investigators disagree, the study chair will make the 
final decision. The Investigative Team will meet regularly throughout the study.  All voting 
members, as well as other investigators will be invited to participate.  
 
3.1.5 UMB Investigational Drug Services (IDS)  
The University of Maryland IDS is responsible for the purchasing, distributing, and accounting 
procedures for all investigational drugs within the University of Maryland Medical Center 
campus and will be responsible for preparing the vitamins/supplements for this project. The 
vitamins/supplements for the study will be purchased and packaged through the University of 
Maryland IDS.  IDS will prepare “treatment kits” for each participant who receives the 
intervention that will include all vitamins/supplements for the 16-week study period: 
1.) 2000 IU vitamin D3, one tablet daily  
2.) 600 mg calcium, one tablet daily 
3.) Multivitamin, one tablet daily 
 
Each treatment kit will contain four individual packs numbered 1-4. Each pack contains a 4-
week supply of vitamin D3, calcium, and a multivitamin. The IDS will prepare appropriate 
packaging for each item in the treatment kit, with a label and directions for taking each product 
that complies with legal requirements. Participants who have contraindications for calcium 
supplementation (i.e., calculated creatinine clearance < 30 ml/min, elevated total or ionized 
calcium, history of kidney stones, primary hyperparathyroidism, or sarcoidosis) will not be given 
calcium. 
 
Protein powder will be ordered by the study and shipped directly to IDS for labeling. The IDS will 
prepare appropriate labeling for each container of protein powder that complies with legal 
requirements. Each participant will receive four 2 lb. containers of protein powder numbered 1-
4.  Each container is a 30-day supply of protein powder. 
 
3.1.6 University of Maryland General Clinical Research Center (GCRC) 
Study staff will conduct assessments for baseline and 16-week follow-up visits at the University 
of Maryland General Clinical Research Center (GCRC), located in the University of Maryland 
Medical Center. The study will utilize GCRC space to draw blood, administer questionnaires, 
and conduct performance measures, including the SMWT. The GCRC will provide blood draw 
supplies and staff to process the screening blood samples.  GCRC administrative staff will also 
assist with reserving space for assessment visits.     
 
3.1.7 Study Clinical Site  
The study has a single clinical site with a PI and coordinator. The clinical site is located at the 
University of Maryland Baltimore (UMB). 
 
Responsibilities of the clinical site PI (with assistance from the coordinator) will include:  
• 
Maintaining cooperation of study hospitals and other recruitment sites and ensuring that 
medical staff involved with the care of hip fracture patients are well informed about the 
trial 
• 
Recruiting study participants according to the study protocol 
• 
Ensuring retention and adherence of study participants 
• 
Performing all study-related assessments (including complete tracking of outcomes 
during follow-up) 

PUSH Plus Protein Pilot Protocol version3.0 
 
8 
• 
Overseeing completion of data collection forms and entering data and processing data 
edit queries  
• 
Training and supervising study staff; assigning tasks to data collectors, PTs, and 
dieticians; and providing day-to-day supervision of their work 
• 
Protecting participant safety and verifying that informed consent procedures are followed 
according to Good Clinical Practice guidelines 
• 
Properly maintaining all study materials and records 
• 
Reporting all RAEs and protocol deviations 
• 
Participating in investigative team meetings and manuscript preparation  
 
Section 4: Study Objectives 
 
4.1 Primary Objective 
The purpose of this study is to test whether adding a protein supplement to the PUSH 
intervention (PUSH Plus Protein) initiated up to 26 weeks pot admission leads to greater 
improvement in a person’s ability to walk in their own home and in the local community 16 
weeks after study entry compared to the PUSH intervention alone; therefore, data in this pilot 
study will be compared to data from participants in the CAP study across the three sites who 
received the PUSH intervention alone (n=105). Our working hypothesis is that PUSH Plus 
Protein will lead to greater improvements in ability to walk in the community compared to PUSH.   
 
4.2 Secondary Objectives 
We will compare the effect of PUSH Plus Protein intervention to PUSH intervention alone on 
secondary outcomes in the CAP study believed to be precursors to community ambulation.  
We can also compare participants in the pilot study to participants who received PUSH alone in 
the CAP-MP study to examine whether PUSH Plus Protein has an impact on the mechanistic 
factors on the pathway to recovery of ambulatory ability after hip fracture. Finally, we will assess 
the safety and tolerability of delivering the PUSH Plus Protein intervention to hip fracture 
patients. 
 
Section 5: Background  
Current standard Medicare-reimbursed rehabilitation therapy fails to restore community 
ambulation to older persons who have had a hip fracture. A residual mobility disability similar to 
that reported for stroke occurs in the majority of persons who “recover” from hip fracture.1,2  In 
contrast to stroke, heart disease, and cancer, there are few intervention trials focused on 
decreasing disability following hip fracture. The paucity of intervention trials is surprising since 
there are over 325,000 hip fractures per year in the U.S.3 with a predicted increase to over 
650,000 per year by 2040.4 The estimated cost to hip fracture patients, their families and the 
health care system is between $14 and $20 billion annually.5-10 A Cochrane Collaboration 
review on interventions post-hip fracture concluded that there is not sufficient evidence to 
determine if the interventions evaluated substantially reduce residual disability and enhance 
community ambulation.11 
 
5.1  Residual Deficits in Precursors of Community Ambulation 
Effective community ambulation requires sufficiency in five physical precursors: endurance; 
dynamic balance; lower limb muscle strength; walking speed; and lower extremity function. The 
precursors enable the person to get up out of bed, get out the front door, and participate in 
community activities. Previous studies indicate significant residual impairments for persons with 
hip fracture who have completed “usual” care.  

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9 
 
Endurance. Deconditioning is expected following a hip fracture, but there is a paucity of 
evidence on aerobic capacity from maximal treadmill or cycle ergometry exercise tests.12-16 The 
only study that examined peak oxygen uptake (VO2 peak) values in 20 persons within a month 
of fracture, reported significantly lower peak values in hip fracture vs healthy community-
dwelling older adults.17 The SMWT has been used as a proxy for aerobic capacity and is 
considered an endurance measure in elderly, frail and severely compromised patients.18  
Performance on the SMWT by persons post-hip fracture closely resembles that of patients with 
New York Heart Association class III or IV heart failure who walk 217 meters on average.19  
Mangione reported average SMWT distances of approximately 200 meters after usual care for 
hip fracture.20 Work in Baltimore and in the pilot study for this trial indicate an average SMWT 
distance of 154 m and 184 m, respectively, at six months post-fracture. This contrasts to 400 
meters reported for 80-year-olds living in the community21 or 350 meters reported for a sample 
of comparable age in the Cardiovascular Health Study.22 
 
Balance. Dynamic balance is compromised after hip fracture. For example, at the end of usual 
care (2-3 months post-fracture), 20% who had regained independence in ADL reported falling; 
those who had fallen since hospital discharge had poorer balance compared to those who had 
not fallen.1,23  Fifty-three percent of patients who were community dwelling pre-fracture fell one 
or more times in the first six months post-fracture and 18% were readmitted to the hospital for 
fall-related injury.1  Balance deficits remain at seven months24 at a time when physical recovery 
is reported to approach a plateau.25,26  
 
Walking  Speed. The proportion of individuals achieving independence in ambulation one year 
post-fracture is between 30% and 83%, depending on the study.27-30   Reasons for the variation 
in reported ambulatory status include the use of different measures, differences in the length of 
follow-up time and different definitions of recovery. It has also been observed that recovery in 
gait speed does not reach a plateau until almost a year post-fracture (Magaziner 2000) 
suggesting that interventions prior to that time might add to the natural recovery process.  
 
Lower Extremity Muscle Strength. Hip fracture is accompanied by rapid loss of muscle mass 
and weakness.31  Muscle weakness is not the sole impairment accounting for extensive residual 
disability post-fracture, but its contribution is significant. Leg, thigh, and hip muscle weakness 
are related to decreased muscle power and walking speed.32-35  Muscle weakness appears, 
therefore, to be a major factor in producing mobility disability.   
 
Lower Extremity Function. A hip fracture results in limited lower extremity function that, in turn, 
compromises physical, instrumental and social function.36,37  At six months post-fracture when 
physical recovery is reported to plateau, a limited proportion of hip fracture patients report 
climbing a flight of stairs (8%) or walking one half a mile (6%).26,38  The majority of patients who 
report independent ambulation also report they do not walk as well they did prior to fracture.25,39  
Even at one year, most hip fracture patients do not return to pre-fracture functional status.26,38,40-
43  They walk more unsteadily and more slowly for shorter distances.44,45  
 
Summary: The numbers and costs of hip fracture are significant, and one to two months of 
usual care is inadequate for restoring function to this patient group.  Most hip fracture patients 
do not regain pre-fracture mobility status. Endurance, dynamic balance, walking speed, lower 
extremity muscle strength, and lower extremity function are compromised and contribute to 
failure to achieve community ambulation. 
 

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10 
5.2 Exercise Studies in Persons after Hip Fracture 
Based on the results of Mangione’s survey of 1000 home care PTs,46 we propose that a reason 
for the residual disability after hip fracture is an inadequate dose of physical intervention during 
usual care. A limited number of investigations have examined the direct effect of physical 
interventions on increasing community ambulation. Only 15 studies were included in a 
systematic review of physical therapy management of hip fracture. 47 A finding relevant to this 
study is that usual care outcomes were similar for home, acute rehabilitation, or skilled nursing 
facilities.  
 
A Cochrane Collaboration review of exercise interventions 11 identified 13 clinical trials in 1,065 
patients and concluded that there was insufficient evidence to determine if physical intervention 
affected outcome post-hip fracture.  Seven trials17,48-53 provided intervention early 
(approximately two months) after hip fracture. Various combinations of low intensity AROM or 
flexibility exercises, functional training, strengthening, and balance exercise did not produce 
outcomes that were different from “usual care” with three exceptions.17,48,49 Since the Cochrane 
review, two additional trials intervened with exercise programs early after hip fracture. One 
offered a one-month intervention focused on falls efficacy and reported initial improvements in 
walking outdoors and ADLs at two months post-fracture.54 Another trial reported no benefit in 
knee extensor muscle strength or walking speed compared to the control group following a 16-
week, home-based strengthening program.55 We believe that differences were not observed 
because the exercise dose was inadequate. This hypothesis is supported by three small trials 
which reported between-group differences and demonstrate that higher intensity exercise can 
be done early and safely. Two of the studies included high intensity exercise very early after hip 
fracture.48,49 Strength, gait speed, balance, and balance confidence improved in the 
experimental groups. The third trial,17 which included aerobic conditioning during in-patient 
rehabilitation, demonstrated improved endurance (VO2 peak), increased mobility, and improved 
balance.  
 
The other clinical trials began six months or later after hip fracture, with interventions that 
included various combinations of strengthening exercise, balance training, functional training, 
and AROM/flexibility. Three of these included endurance training but lacked at least one of the 
other components of the program we are proposing. Results show positive outcomes in terms of 
function, gait speed, balance, strength, and endurance.13,20,56-61  A study conducted in a gym 
demonstrated improvement in self-reported outdoor mobility in the intervention group who were 
four years post-fracture, but no changes in dynamic balance or walking speed.62 Since hip 
fracture recovery is reported to plateau at six months (which is when the interventions in these 
studies began), the results of these studies are comparable to the exercise findings reported in 
older adults without hip fracture, i.e., that older adults benefit from increased activity. These 
studies indicate that use of higher intensity exercise with endurance training beginning six 
months post-fracture reduces impairments in precursors to community ambulation.  
 
The unanswered question is whether a higher intensity program performed as soon as usual 
care is complete will return more people to community ambulation. Mangione described a 
program that provided function, strength, balance, and endurance training to a single patient 
three months post-fracture.63  The patient showed dramatic improvements in all physical 
precursors to community ambulation. In addition, the recent pilot study of the intervention 
resulted in a significant between-group difference in distance walked on the SMWT.  
 
A limited number of studies have examined exercise programs post-hip fracture. The most 
successful in terms of strength, balance, and gait speed outcomes were completed over a 6-
month time period in an exercise center.13,61 The majority of the research published is fraught 

PUSH Plus Protein Pilot Protocol version3.0 
 
11 
with problems including lack of control groups, small samples, and inadequate exercise dose.  
Prior research suggests that more intensive multi-component training as soon as usual care is 
complete should be safe and effective.  
 
5.3 Rationale for the Interventions  
The significant mobility disability that remains post-hip fracture is remarkable and may account 
for failure to return to effective community ambulation. Mangione et al. surveyed physical 
therapists (PTs) nationally to describe usual home care physical therapy following in-patient 
sub-acute care for hip fracture.46 The results indicated very similar care regardless of fracture 
fixation, weight-bearing status, time when physical therapy started, or geographic location. 
Functional training was one of the most frequently reported interventions. Most of the joint-
specific therapeutic exercises reported involved AROM, with very few therapists reporting that 
they used any form of resistance (manual, elastic bands, or weights) for a specific exercise.  
 
This research study is being done to test a 16-week, multi-part exercise intervention for hip 
fracture patients that will be supervised by specially trained PTs. The exercise intervention uses 
a novel machine to provide strength and endurance training in the home. This has been shown 
in smaller studies to be safe and effective at increasing strength. We want to test whether 
adding a protein supplement to the exercise intervention leads to more improvements in a 
person’s ability to walk in their own home and in the local community. With this knowledge, we 
hope to help a greater number of hip fracture patients enjoy a more complete recovery and 
improved overall health.   
 
The research is based on the premise that successful community ambulation requires certain 
factors that are influenced by underlying physical or chemical processes. The key factors 
include endurance, walking speed, muscle strength, balance, lower extremity function, skeletal 
integrity, and fracture healing. We believe that physical activity and protein supplementation can 
impact these factors to improve the ability to walk.  We want to gain a better understanding of 
which factors play a role by performing tests that measure physical function, strength, balance, 
level of inflammation, bone turnover rate, muscle density, and body composition. 
 
PUSH. Older adults improve functional performance when engaging in high intensity multiple 
component interventions.64-70  Despite disagreement about exercise type, intensity, frequency, 
duration, and mechanism, it is known that the older musculoskeletal system adapts to increased 
demand.71  Several randomized trials have reported effects of exercise interventions on 
improved physical function, balance, endurance, mobility and/or falls in community-dwelling 
elders without hip fracture.13,68,69,72-76  Studies reporting positive outcomes had similar content 
(strength, balance, and endurance), used high exercise intensity, and the exercises were 
tailored to the individual’s needs rather than using a generic protocol. Task-oriented functional 
activities72,74 were more effective in achieving positive outcomes than traditional regimens that 
included isometric or isotonic strength training, static standing balance training, and/or cycle 
ergometry.68,73 
 
Principles derived from exercise physiology will be used to determine the intensity of the 
endurance and muscle performance exercises. According to the overload principle, exercise 
should be performed at an intensity higher than the usual load to increase the metabolic 
demand and facilitate a training response.71,77-79  Overload will be achieved by increasing 
intensity (effort or load), or frequency and duration (number of repetitions, number of sets). 
Manipulation of intensity, frequency, or duration alters the exercise dose - heart rate for 
endurance training or the amount of muscle force produced for muscle strengthening.77 A 
review and a meta-analysis emphasize the benefits of endurance training and progressive 

PUSH Plus Protein Pilot Protocol version3.0 
 
12 
resistance training for improvement in functional status, health, and quality of life in older 
adults.80,81 Guidelines suggested by these two reviews recommend combining endurance, 
dynamic balance, and high intensity strength training, which is consistent with the PUSH 
intervention.  
 
The specificity of training principle has been neglected in many hip fracture intervention 
programs. Research suggests that the type of muscle contractions used during exercise should 
match the type of contractions used in the desired activity to achieve the most gain.71,77  The 
multi-component PUSH intervention will address endurance by requiring completion of task-
specific activities for a continuous period of time. Muscle training will be addressed using a 
machine that provides progressive resistance training while the lower extremity performs whole 
limb patterns similar to those used in walking. Upright balance will be challenged in combination 
with muscle training.  Although there is evidence that appropriate training increases endurance 
and muscle performance, the mechanisms for adaptation in response to exercise in older adults 
are still being clarified.82-86  Motor learning principles, theories associated with neural plasticity 
and exercise physiology must all be considered in the design of an intervention focused on 
increasing community ambulation.71 The older person with hip fracture is more complex 
because of the significant newly acquired deconditioning, muscle atrophy, fracture healing, and 
other metabolic changes. 
 
Protein.  It is hypothesized that the addition of protein will have a beneficial effect on some of 
the mechanisms on the pathway to community ambulation, specifically muscle and bone. 
Resistance exercise is a powerful stimulus for muscle protein synthesis.87-89 and a weaker 
stimulus for muscle protein breakdown, the net effect of which is a positive protein balance.88 
Protein intake is required to allow muscle protein synthesis in response to resistive exercise. 
Supplementation with protein or essential amino acids (EAAs) has been shown to simulate post-
exercise muscle protein synthesis, and to improve net protein balance,90,91 with supplementation 
immediately after exercise resulting in greater quadriceps cross-sectional area and strength 
compared to supplementation two hours after exercise.92 Skeletal muscle remains catabolic 
post-exercise without the presence of the branched-chain amino acid (BCAA) leucine.93  
Supplementation with BCAAs also has been found to reduce muscle soreness resulting from 
strenuous exercise.94,95  Although healthy older adults who habitually consume adequate 
amounts of dietary protein (>0.8 g/kg/d) may not benefit from further protein supplementation 
with resistance training,96,97 many elderly hip fracture patients are in a state of protein depletion 
at the time of fracture and have low protein intake post fracture.98,99 
 
Data supporting a positive effect of protein supplementation on bone health as measured by 
BMD and markers of bone turnover come from two reviews.100,101  Two studies in elderly hip 
fracture patients used a protein supplement containing 20 gm per day.102,103 The proposed 
mechanism underlying the association between protein supplementation and improvement in 
bone health is mediated by increases in IGF-1 and both total and free testosterone levels,104,105 
resulting in greater bone formation. This pilot study will test if the addition of a protein 
supplement immediately following exercise will enhance the mechanistic effects seen with 
exercise. 
 
5.4 Primary Outcome Measure 
Community ambulation is a construct that includes the ability to accommodate change in level 
and terrain irregularity (necessary to enter and leave the home and for curb management), 
avoid obstacles and walk a requisite distance.106  Compared to older adults who are active in 
the community, persons with a mobility disability do not travel alone, take fewer trips and 
perform fewer activities per trip, walk shorter distances, cross the street less often, carry fewer 

PUSH Plus Protein Pilot Protocol version3.0 
 
13 
objects, and have fewer postural transitions (turning the head, extending their reach, or 
changing direction).107  Although community ambulation is complex, covering a minimal distance 
within a specified period of time is a critical feature.108,109 
 
The SMWT is a standardized test that examines both the distance and time components of 
community ambulation.110 The Cardiovascular Health Study111 concluded that the SMWT is safe 
for use in community samples to measure the impact of multiple comorbidities on endurance in 
older adults.22  Harada et al 112 proposed that the SMWT is a useful integrated measure of 
mobility function taking into account any limitations imposed by major body systems.112  Lord 
and Menz113 concluded that the SMWT provides a measure of overall mobility and physical 
function in addition to being a measure of cardiovascular fitness. Sixty-nine percent of the 
variance in the SMWT is explained by physical functioning, lower body strength, standing 
balance, and gait speed.112  Construct and predictive validity and responsiveness to change 
were established for the SMWT in a sample of 108 persons with hip fracture.114 A high positive 
correlation was reported between pedometer-determined physical activity and the SMWT test 
suggesting that both are correlates of community ambulation.115 The SMWT also has been used 
as an outcome measure to determine the effectiveness of exercise interventions for elderly 
patients with and without hip fracture.20,56,116 In addition to the distance walked in six minutes, 
gait speed will also be derived. The primary end point for this pilot study is the total distance 
walked in six minutes.    
 
 
Section 6: Study Design 
 
6.1 Overview of Study Design 
A pilot study including 30 older adults who have experienced a hip fracture will be carried out 
with participants receiving a specific multi-component intervention with protein supplementation 
(PUSH Plus Protein).  Study activities for participants meeting eligibility criteria will take place 
after post-acute rehabilitation ends, up to 26 weeks after admission to the hospital for hip 
fracture. Patients age 60 and older who have had surgical repair for hip fracture will be identified 
in study hospitals or by self-referral and evaluated for eligibility. Following consent to participate, 
eligible participants will undergo a comprehensive baseline assessment. Participants completing 
the baseline assessment will be eligible to receive the intervention.  All participants will receive 
the PUSH Plus Protein intervention.  The follow-up assessment will occur after the intervention 
is completed, approximately 16 weeks after baseline testing. Figure 1 shows the sequence of 
participant contacts from the time of hospitalization until the 16-week assessment. 
 

PUSH Plus Protein Pilot Protocol version3.0 
 
14 
Figure 1. Timeline for screening and follow-up 
 
Within a week of complete baseline testing, the physical therapist (PT) will initiate the exercise 
intervention and the protein supplement in the home setting. Participants will also receive 
counseling with a registered dietician. The follow-up assessment will take place 16 weeks after 
baseline testing. Telephone interviews will be conducted every four weeks, beginning four 
weeks after baseline testing, to obtain information about RAEs and expected AEs, and to help 
reduce loss to follow-up by maintaining ongoing rapport with participants. An honorarium will be 
given at the completion of both study assessment visits. 
 
6.2 Interventions 
Over a 16-week period, participants will receive two visits per week from a study PT, on non-
consecutive days, for a total of 32 visits. These visits will take place in participants’ place of 
residence. Participants will be given a whey-based protein supplement containing 27.6g of 
protein to be taken daily. Participants will also receive 2,000 IU of vitamin D3, 600 mg of 
calcium, and a multivitamin daily during the 16-week study period and counseling with a 
registered dietician to ensure body weight stability and adequate nutrient intake inclusive of a 
healthy diet. 
 
Section 7: Selection and Enrollment of Participants 
 
7.1 Eligibility   
Participants will be evaluated for eligibility in three phases (see Figure 2), all of which must be 
completed no more than 26 weeks after admission to the hospital for a hip fracture.  In phase 1, 
patients will be assessed for inclusion criteria and medical exclusions. Information for phase 1 
will be collected from the patient’s medical chart.  A HIPAA Partial Privacy Waiver (for 
recruitment) or verbal consent to review the medical chart for eligibility will be obtained for 
patients who are identified at study hospitals up to 26 weeks after their admission for hip 
fracture; this includes patients who were admitted to the hospital for hip fracture up to five 
months prior to the start of screening.   
 
Hospital 
admission 
 
Baseline testing 
16-week 
follow-up 
Eligibility 
screening  
(3 phases) 
 
16-week intervention 
Telephone interviews every four weeks 

PUSH Plus Protein Pilot Protocol version3.0 
 
15 
Patients who are provisionally eligible based on medical chart review at phase 1 will be 
approached or contacted by telephone to be told about the study in the hospital or after 
discharge (up to 26 weeks after admission for hip fracture).  Interested patients who are 
approached in the hospital or rehab will be asked to provide written Permission to Contact for 
additional screening. If we are unable to get written Permission to Contact while the patient is 
still in the hospital, we will contact patients via telephone to determine their interest in the study 
and obtain verbal Permission to Contact for additional screening. Patients who are identified 
through other means of recruitment (e.g., patients who call the study office in response to 
advertising or physician referral) will undergo a brief pre-screening over the telephone. 
Potentially eligible patients who are interested in participating will be asked to provide written 
authorization for release of medical records for review of phase 1 eligibility criteria. Those who 
agree to further contact will be screened in phase 2 to assess for medical, safety, and feasibility 
criteria. Informed consent must be obtained prior to any further data collection or research 
procedures beyond phase 1 screening criteria. 
 
Blood will be collected and tested for hemoglobin (<9 g/dl), serum creatinine to calculate 
creatinine clearance (<15 ml/min or 15-29 ml/min), serum albumin (<2.5 g/dl), and hemoglobin 
A1c level (>10%). The blood collection can occur anytime between phases 2 and 3 screening 
as long as it occurs after informed consent is obtained and no more than 4 weeks prior to 
baseline testing. 
 
Phase 3 will assess final eligibility at the clinical site center at the beginning of the baseline visit. 
Phase 3 must be completed no later than 26 weeks after admission to the hospital for hip 
fracture.  Phase 3 will include a review of all disqualifying medical conditions, assessment of 
cognitive status with the Modified Mini-Mental State examination (3MS), and evaluation of ability 
to walk 300 meters in six minutes. This final test will be used to exclude participants who are 
unlikely to benefit from the study interventions because their gait speed is very low (<0.1 m/s) 
and to exclude those who are able to walk 300 m or more in six minutes and are, therefore, 
already classified as community ambulators. The study physician must review all study eligibility 
documents and sign off on final eligibility for all potential participants prior to collection of 
baseline data. All participants will be seen by the study physician.   
 
Eligible individuals will receive the baseline assessment consisting of questionnaire items, DXA 
and CT scans, and testing of strength, balance and functional performance.   
 
7.1.1 Required Baseline Data   
 
Certain components of the baseline assessment must be completed by all participants in the 
pilot study in order to make useful comparisons to data from participants in CAP and CAP-MP 
and to have enough power to achieve primary and secondary research aims.  Participants who 
perform the required components (identified in Section 10: Study Procedures) no later than 26 
weeks after hospital admission for the hip fracture will be said to have complete baseline data 
and thus be eligible to receive the PUSH Plus Protein intervention.   

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16 
 
 
7.2 Inclusion Criteria (Target Population) 
1.  Minimal trauma, non-pathologic hip fracture with surgical repair 
1.1  Closed fracture of proximal femur 
1.2  Minimal trauma fracture 
1.3  Surgical fixation of fracture   
1.4  Non-pathologic fracture  
  
2.   Age 60 or older 
2.1  Age 60 or older at time of baseline testing 
 
3.  Community ambulation 
3.1  Living in the community at time of fracture 
3.2  Ambulating without human assistance two months prior to fracture 
3.3 
Unable to walk 300 m or more in six minutes without human assistance at time of 
baseline testing  
 
7.3 Exclusion Criteria 
 
4. Logistical impediments to participation 
4.1. Does not live within reasonable distance of the clinical center 
4.2. Participant plans to move out of area or otherwise be unavailable during the 16-week 
intervention period 
4.3. Participation in another clinical trial  
4.4. Not English speaking 
4.5. Baseline testing not completed by 26 weeks post admission for hip fracture 
4.6. Final sign off from study physician and/or principal investigator is incomplete 
4.7. Incomplete baseline data 
4.8. Unable to contact participant 
4.9. Participant is unable to provide her/his own informed consent 
4.10. Participant refuses the study 
 
5. Medical impediments to participation or low potential for benefit from interventions 
5.1. Calculated creatinine clearance < 15 ml/min 
5.2. Serum albumin < 2.5 g/dl 
      Figure 2. Algorithm for Screening  
Not Eligible  
No 
  Yes 
No 
  Yes 
No 
Intervention 
Phase 1 Screening  
Chart Review  
Phase 2 
Screening 
Interview 
Phase 3 Screening  
 
Exclusion Criteria 
3MS score below 73 
SMWT <4 m in 40 sec  
or ≥300 m in 6 mins 
Yes 
No Intervention 
Complete  
Baseline Data 
  No 
Screening Blood Draw 
Exclusions 
  Yes 
Exclusion Criteria   
 Hemoglobin <9 g/dl 
Calculated creatinine clearance  
<15 ml/min or 15-29 ml/min 
    Serum albumin <2.5 g/dl 
Hemoglobin A1c level >10% 
  Yes 
No 
Exclusions 

PUSH Plus Protein Pilot Protocol version3.0 
 
17 
5.3. End stage renal disease on dialysis (CKD stage 5 or 6) 
5.4. Lower extremity amputation 
5.5. Cognitive impairment (3MS score <73) 
5.6. Severely diminished lower extremity sensation or ulceration  
5.7. Participant walks less than four meters in 40 seconds (<0.1 m/sec) 
5.8. Not community-residing (e.g., resident of a skilled nursing facility) at time of baseline 
testing  
5.9. Receiving PT  for the hip fracture in the hospital or in an inpatient rehabilitation facility 
at time of baseline testing 
 
6. Medical contra-indications for exercise 
6.1. Hemoglobin < 9 g/dl 
6.2. Symptoms of angina pectoris  
6.3. Recent myocardial infarction  
6.4. Uncompensated congestive heart failure  
6.5. Chest pain or shortness of breath (including from severe chronic obstructive 
pulmonary disease) 
6.6. Uncontrolled hypertension 
6.7. Not fully weight-bearing on fractured leg or non-fractured leg at time of baseline 
testing 
6.8. Study physician thinks participant is not a good candidate for study (e.g., not likely to 
survive study period) 
6.9. Development of chest pain or substantial shortness of breath or ambulating with 
severe pain during baseline SMWT 
 
7. Medical contra-indications for whey protein supplement 
7.1. Chronic kidney disease (CKD stage 4) 
7.2. Severe liver disease (e.g., hepatitis, fatty liver disease, cirrhosis) 
7.3. Hemoglobin A1c level > 10% 
7.4. Known dairy allergy 
7.5. Known celiac disease 
7.6. Known history of severe, life-threatening peanut or shellfish allergy 
7.7. Calculated creatinine clearance 15-29 ml/min 
 
7.4 Identification of Hip Fracture Patients 
Potential participants will be identified directly from study hospitals, rehabilitation centers, or 
agencies that care for older adults or they may contact the study directly in response to other 
recruitment methods such as study recruitment flyers, advertisements, or referral from a 
clinician (orthopedic surgeon, physical therapist).   
 
Study hospitals will be chosen based on 1) number of hip fracture patients per hospital per year 
and 2) geographic proximity between hospitals and clinical site.  We will review the number of 
participants recruited in each hospital on a regular basis and initiate enrollment in one or more 
other hospitals if recruitment numbers are lower than expected. We will obtain approval of our 
study protocol from the UMB IRB and from each study hospital.  
 
7.5 Informed Consent 
Written informed consent and appropriate HIPAA authorizations and/or waivers will be obtained 
in compliance with procedures reviewed and approved by the UMB IRB and study hospital IRBs 
prior to any data collection. Informed consent can be obtained anytime upon completion of 
phase 1 eligibility screening and prior to 26 weeks post hospital admission. Regardless of when 

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informed consent is obtained, study staff will follow the Good Clinical Practice guidelines for 
informed consent. A copy of the informed consent form (ICF) will always be provided (either in 
person or by mail) to potential participants to allow for adequate review of the information and to 
allow review with family members. Prior to obtaining informed consent, time will be given to the 
potential participant to review the consent form and ask questions. If a participant has vision 
impairments that prevent her/him from reading the ICF, the consent form will be read aloud to 
them and the informed consent process will be witnessed. The witness should also sign and 
personally date the consent form attesting that the information in the consent form and any 
other written information was accurately explained to, and apparently understood by, the 
participant and that informed consent was freely given. Even when the participant reads the 
consent form on their own, study staff will summarize all components of the ICF and remind 
potential participants that participation in the study is voluntary and that s/he has the right to 
withdraw at any time. It will also be explained that signing the consent form allows the study to 
confirm final eligibility before receiving the intervention. The consent process will be performed 
without the use of any coercive language or behavior, and with respect for the person's 
autonomy.  
 
The goal of the informed consent process is to increase potential participants’ understanding of 
the study in order to better enable them to decide whether or not to enroll.  Therefore, every 
effort will be made to help potential participants understand the research project.  During the 
informed consent process, study staff will provide participants with adequate information 
concerning the study procedures, respond to questions and concerns, and ensure that each 
individual understands all the information provided by assessing ability to provide informed 
consent.   
 
Potential participants who choose to enroll will be assessed for their ability to provide informed 
consent using the Evaluation to Sign Consent measure.  Individuals who do not understand the 
study purpose, methods, risks, and benefits are not able to provide their own informed consent 
and will not be eligible for participation. The informed consent process will be documented by 
including the following information in the research records: that the study was explained, 
questions (if any) were answered, ability to provide informed consent was assessed, subject 
agreed to participate and signed the consent form and HIPAA Authorization, the presence of a 
witness for individuals with hearing or vision impairments, and a copy of the signed consent 
form and HIPAA Authorization was given to participant and, if necessary, left in the chart of 
facility.  For people who provide informed consent, the original signed ICF will be submitted to 
the study office and a copy of the signed ICF will be given to the participant.  If the person 
provided consent while in a medical facility, a copy of the ICF will go into her/his chart. The PI 
and/or designee will ensure the accuracy, completeness, legibility, and timeliness of the 
informed consent process conducted by the study staff before any phase 3 eligibility data are 
collected. 
 
7.5.1 Enrollment 
Date of enrollment in the trial is defined as the date of informed consent. 
 
7.6 Monitoring Recruitment and Retention 
Study investigators will monitor recruitment and retention activities throughout the study. We will 
review the number of patients screened relative to the number of participants recruited through 
each recruitment source quarterly and initiate additional enrollment strategies if recruitment 
goals are not being met. 
 

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At the completion of baseline testing, participants will receive written instructions about the 
schedule of follow-up assessments, PT intervention visits, dietician contact, and four-week 
telephone interviews. To maintain rapport, the same staff member will, whenever possible, 
contact and visit the participant throughout the study. Minimizing waiting time, providing free 
transportation for the baseline and follow-up assessment, and providing comfortable waiting 
room facilities make the visits more pleasant, thereby enhancing participant retention at follow-
up. If participants are unable to come to the clinical site for the follow-up assessment, a visit at 
another location (home or another facility) will be scheduled. Telephone interviews will be 
scheduled if in-person visits cannot be completed. 
 
Some participants may not actively participate in the study, either by declining the intervention 
visits and/or by not participating in telephone calls or the follow-up assessment. These 
participants will be followed until the end of the study unless they explicitly request not to be 
contacted. Study staff will make contact every four weeks in order to remind the participant that 
he or she is welcome to rejoin the study at any time. Also, considerable effort will be expended 
to collect data on the primary outcome at the follow-up assessment. 
 
Section 8: Study Interventions 
 
8.1 Overview 
Participants will receive two physical therapy visits a week, on non-consecutive days, for a total 
of 32 visits and be given a whey-based protein supplement containing 27.6g of protein daily for 
16 weeks. Each visit will last approximately 60 minutes. Participants will also receive 2,000 IU of 
vitamin D3, 600 mg of calcium, and a multivitamin daily during the 16-week study period and 
counseling with a registered dietician to ensure body weight stability and adequate nutrient 
intake inclusive of a healthy diet. Missed visits can be replaced during subsequent weeks if 
there is at least one day in between visits and no more than three visits in the week. Visits will 
take place in the participant’s place of residence. 
 
8.2 Nutritional Support 
Given the importance of ensuring adequate nutrition to those who receive the intervention, we 
will provide all participants with 2000 IU of vitamin D3, 600 mg of calcium, and a multivitamin 
daily for the duration of the 16-week study and nutritional counseling to ensure weight stability, 
adequate nutrient intake of 1 g protein/kg body weight inclusive of a healthy diet (50% 
carbohydrate, 20% protein, 30% fat).  Participants will be screened at the time of baseline 
testing to assess nutritional risk using the Mini Nutritional Assessment-Short Form (MNA®-
SF).117 Those who score ≤7 (malnourished) at baseline and participants with serum albumin 2.5-
3.5 g/dl (regardless of the score on MNA®-SF) will receive a visit from a registered dietician 
(RD) in their place of residence within seven days of baseline testing. The RD will evaluate and 
counsel them on making dietary modifications based on their protein, caloric and other dietary 
deficiencies using a standardized approach across the three study sites.118-120 The RD will follow 
up with participants by telephone one week after the visit to assess understanding and 
implementation of recommendations. Participants who score 8-11 (at risk of malnutrition) at 
baseline and have serum albumin level >3.5 g/dl will receive a telephone dietary consultation 
with the RD within seven days of baseline testing. Based on the participant's eating habits and 
food intake, the RD may make the clinical determination that an in-person consultation is 
warranted. In these cases, the RD will schedule an in-person dietary consultation, following the 
same protocol as those who score in the malnourished range. Those with a score ≥12 on the 
MNA®-SF and who have serum albumin level >3.5 g/dl at baseline will receive brief telephone 
contact within seven days of baseline testing from the RD to discuss the importance of calorie 

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and protein intake. Weight will be monitored during home PT visits every four weeks and those 
who lose 2% or more body weight in a four-week period will receive another telephone 
consultation by the study RD. This protocol applies to anyone who loses 2% or more of body 
weight, regardless of whether the participant is trying to lose weight.  Vitamin D, calcium, and 
multivitamin adherence will be reviewed by the PT every four weeks (by pill counts) and 
assessed by self-report every four weeks by telephone interview.   
 
8.3 PUSH Intervention 
This intervention is based on improving specific precursors to community ambulation by 
addressing endurance with continuous upright exercise for 20 minutes in duration; function such 
as walking, standing from a chair, and stair negotiation; muscle performance by exercising to 
enhance lower extremity strength and power in functionally relevant muscles moving through 
locomotion-appropriate movements and ranges; and balance by performing unilateral activities 
and activities with decreased base of support. These components of exercise will be woven 
together into one program that minimizes participant burden. By the end of the first eight weeks 
participants will be instructed to complete the endurance component independently one to two 
times/week by walking for a similar duration and intensity as they have been doing with the PT 
during the supervised visits.  
 
The strength components of the muscle performance intervention will be performed using a 
portable progressive resistive exercise device (Shuttle® MiniPress, Contemporary Design 
Company, P.O. Box 5089, Glacier, WA 98244). The device has six latex bands each with a 
starting load equal to approximately seven pounds. At full excursion one band can provide 
approximately 15 pounds of force. These bands provide the resistance and are attached to the 
machine by a slotted bar on the frame. Inserting more bands into the slotted bar increases the 
resistive load for the participant. A progress monitor strip is located on the top of the machine 
frame. Strips indicate resistance by showing distance that the load is moved. The resistance 
numbers indicate the force for one band as the carriage is moved. When more than one band is 
used, the values will be added.121 
 
Muscle performance will focus on bilateral hip extensors, hip abductors, knee extensors, and 
plantar flexors because of their role in function, specifically gait and transfer activities.122-124  Hip 
and knee extensor muscle will be trained to work hard and fast during the leg press motion 
since this mimics the functional activity of rising from a chair or going up a step. Hip abductors 
will be trained in 5° of adduction and to 10-15° of abduction. Fifteen degrees of movement was 
chosen because it approximates the 8° of motion associated with gait and takes into account 
variations in hip positions while standing.125  Hip extension will also be trained in standing from 
35° of flexion to extension to a neutral position. This ROM approximates the time in the gait 
cycle when the gluteus maximus shows the highest muscle activity, i.e., from heel contact 
through 20% of stride.123  Plantar flexors will be strengthened in standing against body weight68 
because of their role in the push-off phase of gait and the strong association of  plantar flexion 
power and walking speed.68,122-126  The intensity of strength training will be determined during 
Day 1 of intervention at the participant’s residence. The PT will determine the amount of 
resistance the participant can push against so that s/he can complete a maximum of eight 
repetitions (eight repetitions maximum (RM) or 8-RM). 8-RM was chosen because it is strongly 
related to the 1-RM127 and determining the 8-RM will allow the PT to know the training intensity 
without further sub-calculations (e.g. 80% of the 1-RM). Studies have shown that the 8-RM is 
more effective than training at 10-RM or 2-RM79 yet is not so aggressive that it is associated 
with injuries.128,129 This protocol has been used safely and effectively in elders12,64,65,68,124,130 and 
specifically in persons post-hip fracture.20,63 For the first visit, participants will be tested to find 
the load associated with an intensity of 8-RM.  During the second session, participants will 

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perform 2 sets of 
8 repetitions at 
the 8-RM 
intensity. From 
the third session 
through the 
remainder of the 
program, 
participants will perform 3 sets of 8 repetitions at an intensity of the 8-RM. The PT will provide 
strong verbal encouragement during each repetition for the participant to move as “fast and as 
hard as possible” during the concentric phase and to move slowly and in a controlled way in the 
eccentric phase. Intensity will be reviewed every two weeks. 
 
The participants will be supine for two exercises: the combination of hip and knee extension 
exercise (leg press) and the hip abduction exercise (Figure 3a & 3b). The device will be placed 
on the bed or floor (if the participant is able to be assisted safely to and from the floor) so that 
the participant’s foot will rest on the footplate and the hip will be flexed to 90°. The participant 
will push the leg out into full hip and knee extension against the pre-determined resistance. For 
the hip abductors, the participant will start in 5° of adduction and move 15° into abduction. The 
participant’s foot will be strapped to the footplate as the participant moves the leg outward.  
 
Balance and strength will be addressed with two additional exercises performed in standing. 
Balance will be addressed by asking the participant to perform one-legged activities or to stand 
upright with a decreased base of support. The first exercise that combines balance training and 
strength training will be standing hip extension (Figure 3c). The leg will be flexed approximately 
35° of flexion and the participant will extend to neutral position. Upright balance will be 
challenged as the participant moves the carriage of the exercise device with one leg as the 
other leg maintains stability. 
 
The second exercise that combines balance and strength training will be standing plantar 
flexion. Initially, participants will be asked to decrease their standing base of support by rising 
onto the balls of feet. This exercise also strengthens the plantar flexors. Balance and strength 
will be progressively challenged by advancing the activity to unilateral heel raises. For hip 
extension and plantar flexion, the person may hold lightly onto an assistive device for balance or 
support. The PT will encourage the participant to use less external support for balance during 
each session. Resistance (load in pounds) and repetitions for each exercise performed will be 
recorded in a training log.20   
 
HR will be measured by palpation of the radial artery recorded every five minutes and it will be 
averaged over 20 minutes of continuous exercise. The PT will calculate the HR training zone 
based on the heart rate reserve (HRR) method (HR max-HR rest) multiplied by 50% and then 
added to HR rest. HR max will be calculated as 220 minus the participant’s age. This 
prescription is consistent with moderate intensity exercise and has been shown to increase 
aerobic capacity in elders.131-133 If the person is taking medication that controls heart rate (e.g., 
beta-blockers), Borg’s Rating of Perceived Exertion (RPE) scale will be used.134  The training 
intensity using the RPE scale will be “moderate” work as consistent with a 3-5 on the 0-10 scale.   
 
The endurance intervention will begin initially with two to three minutes of continuous upper and 
lower extremity AROM with the participant sitting. These exercises are intended to increase the 
participants’ HR or exertion closer to the target zone. The participant will then be asked to walk 
on level surfaces and up and down one or more steps, if able and available, to keep the HR 
Figure 3. Shuttle Device (arrows indicate direction of lower extremity motion) 
 
 3a
3b  
3c

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within the training zone for 20 minutes. The PT can also engage the participant in additional 
exercises such as upper and lower extremity AROM exercises to keep the HR elevated. The 
target HR will be 30% of HRR in the first week of the program, 40% of HRR in the second week, 
and 50% of HRR in weeks 3 through 16. 
 
8.4 Protein Supplement 
Participants will receive a whey-based protein supplement containing 27.6g of protein. This 
dose induces maximum muscle protein synthesis post-exercise.[130] Participants will mix the 
supplement in 8 oz of water (or other beverage) or soft food (e.g., yogurt, soup) and consume 
immediately following each exercise session with the study PT. On days when they do not have 
a physical therapy visit with the study PT, participants will be instructed to take the supplement 
at the meal time closest to the time of scheduled PT visits to maintain regular daily dosing 
schedule.   
 
8.5 Treatment Fidelity Plan 
Treatment fidelity135,136 will be evaluated with regard to: (1) design, which focuses on whether 
the intervention (PUSH plus protein) is consistent with underlying theories, and whether the 
study is free of contamination such as unintended motivational interventions; (2) training, which 
addresses skill acquisition and maintenance in PTs; (3) delivery, or the assessment that the 
intervention was implemented as intended; (4) receipt, which focuses on whether or not the 
participant understood and received the intervention as intended.  Overall, treatment fidelity 
data will provide information on the adherence of the PTs to the intervention, and the adherence 
of the participants to the prescribed activities.  Monitoring treatment fidelity also will provide an 
opportunity to address potential study problems, such as drift from the intervention protocol 
which could threaten the study’s ability to detect treatment effects. 
 
8.5.1 Initial Training for Procedural Reliability 
The Intervention Monitor (IM) will train PTs in PUSH intervention procedures. Knowledge of 
procedures will be tested by written examination and by psychomotor skills observation via 
video.  The IM will document that PTs are “certified” and provide a certificate of completion after 
they demonstrate competence on the written exam and video observation.  PTs also need to 
bring evidence to the training session that they are currently CPR certified. As new PTs join the 
study, training will be conducted on an individualized basis following the same procedures.   
 
8.5.2 Ensuring Ongoing Competency  
We will use a multi-faceted approach to ensure ongoing treatment fidelity.  The approaches 
include direct observation of skills by the IM, mandatory monthly telephone calls with all active 
PTs, periodic review of PT log books, and access to online discussion boards.  
 
Direct Observation: Direct observations of PTs as they perform the intervention will be 
conducted by the IM. The IM will document observations using a structured checklist that 
addresses data completeness, physical performance, qualitative observations, and verbal 
and non-verbal communication. The checklist will also document whether the participant 
completed the necessary repetitions at the appropriate intensity and whether the participant 
completed 20 minutes of aerobic exercise at the proper intensity. There will be two 
observation visits during the PT’s first assigned participant’s 16-week intervention period 
and then one observation per quarter for PTs who have conducted a complete 16-week 
intervention period for at least one participant. If the total score on the checklist is less than 
90%, the PI will be notified. A remediation plan will be proposed that will offer refresher 
training to ensure accurate understanding of the protocol, follow-up observation visits, and 
possible dismissal if warranted.    

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23 
 
Mandatory Conference Calls with PTs: The IM will conduct monthly telephone calls with the 
PTs who are currently active with participants and take minutes of the telephone meetings to 
document ongoing training. During these calls, the IM will ask questions to identify problems 
with delivering the intervention. If problems are identified, the IM will schedule an individual 
telephone call and review of PT log books. Additional follow-up will be mandated if there are 
modifications to the exercise prescription that are due to PT factors. A remediation plan will 
be followed if there is ongoing lack of progress. 
 
Periodic Review of Intervention Logs: The IM will review PT intervention logs on a regular 
basis to confirm that PTs are completing logs correctly and identify whether there are 
modifications to the intervention protocols. This information will be discussed during the 
monthly phone calls.  
 
8.6 Scheduling Intervention Visits 
There are three requirements for scheduling of intervention visits:  
1. The first intervention visit should occur on Day 7 or earlier, where the last day of baseline 
testing = Day 0.    
2. The schedule of intervention visits is anchored to the date on which baseline testing is 
completed regardless of when the intervention starts.   
3. Intervention visits should never occur on two consecutive days, even when moving from one 
week to the next. 
 
Participants who provide required baseline data are eligible to receive the intervention; however, 
the intervention will not begin until after the date all baseline measures are completed. Baseline 
data collection must be completed within 14 days of the SMWT.  Week 1 will begin on the day of 
the first intervention visit or on Day 7 after baseline testing is complete, whichever is earlier.  
Subsequent weeks will start on the same day of the week as Week 1. For example, if the 
participant’s first intervention visit is on a Wednesday, each intervention week for that participant 
will extend from Wednesday to Tuesday (inclusively).  Alternatively, if the first visit has not yet 
occurred by Day 7 and Day 7 is a Monday, then the participant’s intervention weeks will extend 
from Monday to Sunday (inclusively). 
 
In certain circumstances (e.g., illness, travel), the first intervention visit may be scheduled after 
Day 7. 
 
Ideally participants will receive 2 visits per week for 16 weeks after complete baseline testing 
(32 visits total). However, missed visits in a given week can be replaced by makeup visits in 
subsequent weeks (not to exceed 3 visits in any given week) as long as the visits are on non-
consecutive days. If the participant has not had 32 visits by the end of 16 weeks, makeup visits 
can be performed during the subsequent two weeks to get as close as possible to the target of 
32 visits. 
 
Section 9: Study Measures 
A list of study measures is provided below. All of the measures will be interview-based or based 
on observations of performance or physiological assessments. No proxy data will be allowed at 
baseline. However, at the 16-week follow-up visit, a proxy may be contacted to provide 
information about the participant’s walking ability. Also, the four-week phone calls to obtain 
information on recent health events will be conducted with a proxy when the participant is not 
available 

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24 
 
9.1 Screening Evaluations 
There will be three primary components to the screening process: the chart review in the acute 
care setting (phase 1), the phase 2 screen, and screening for final eligibility (phase 3) that 
includes the 3MS and the SMWT.  These components will be typically administered over three 
contacts.  Those who qualify after phases 1 and 2 will be invited for the first study visit for phase 
3 screening. 
 
9.1.1 Modified Mini-Mental State Examination (3MS) 
The 3MS is a test of global cognitive function which assesses a broad variety of cognitive 
dimensions and is an expanded 100 point version of the original Folstein Mini-Mental State 
Exam.137,138 The 3MS will be used at the baseline visit to identify and exclude participants with 
cognitive impairment (3MS score <73).139     
 
9.2 Primary Outcome Measure: Community Ambulation 
The Six-Minute Walk Test (SMWT) will be used to obtain a continuous measure of total distance 
walked in six minutes. The SMWT is highly correlated with workloads, heart rate, oxygen 
saturation, and dyspnea responses when compared to bicycle ergometry and treadmill exercise 
tests in older persons. It has been performed by elderly, frail and severely compromised 
participants who cannot perform standard maximal treadmill or cycle ergometry exercise tests. 
Performance of the SMWT at the baseline assessment also will be used to define final eligibility 
prior to the collection of additional baseline data.  Participants who walk less than four meters in 
40 seconds (<0.1 m/sec) or who walk 300 meters or more in six minutes will be excluded from 
the trial.  Participants with angina, extreme shortness of breath, or ambulating with severe pain 
during the SMWT also will be excluded. 
 
Participants will be asked to walk back and forth on a measured path marked clearly at both 
ends for turning purposes, while being told when each minute has passed, and receiving verbal 
encouragement (“you’re doing well” or “keep up the good work”) every 60 seconds. Test-retest 
reliability in older adults is excellent (r = .95).112 Concurrent validity with V02 peak (r=.64) and 
cycle ergometry (r=.58) have been reported.110,140,141   
 
9.3 Secondary Outcome Measures  
 
9.3.1 Cognitive Function (3MS) 
The Mini Mental Status Exam (MMSE) is one of the most widely used screening instruments for 
dementia. The Modified Mini-Mental State (3MS) test was developed to overcome shortcomings 
of the MMSE, specifically its narrow range of possible scores and ceiling effects. The 3MS 
incorporates four additional items (on long-term memory, abstract thinking, category fluency, 
delayed recall), more uniform administration, and refined scoring, in order to sample a broader 
variety of cognitive functions, cover a wider range of difficulty levels, and enhance the reliability 
and validity of the test scores. The 3MS test has a score range of 1-100. It can provide an 
estimated score of the MMSE, and can also be used to monitor cognitive change over time. 
 
9.3.2 Short Physical Performance Battery (SPPB) 
The SPPB evaluates lower extremity performance in older persons based on timed short 
distance walk, repeated chair stands, and a set of balance tests.142-144  Each of the tasks is 
assigned a score ranging from 0 to 4, with 4 indicating the highest level of performance and 0 
an inability to complete the test.  The test takes about 10-15 minutes to administer and was 
designed to be administered by a lay interviewer in a setting with limited space.  The battery has 

PUSH Plus Protein Pilot Protocol version3.0 
 
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an excellent safety record. It has been administered to well over 10,000 persons in various 
studies and no serious injuries are known to have occurred. The SPPB components and total 
score are derived from normative values obtained from a population-based study.142,144  The 
total score ranges from 0 to 12; there are three subscales embedded in the SPPB.   
 
Standing balance. For the test of standing balance, participants are asked to maintain 
balance in three positions, characterized by a progressive narrowing of the base support: 
with feet together (side-by-side position), the heel of one foot beside the big toe of the other 
foot (semi-tandem position), and the heel of one foot in front of and touching the toes of the 
other foot (tandem position). For each of the three positions, participants are timed to a 
maximum of 10 seconds.   
 
We will use an enhanced balance measure that includes the balance subscale of the Short 
Physical Performance Battery (SPPB) and two additional single leg stands (eyes open and 
eyes closed), as used in the National Health and Aging Trends Study (NHATS).160  For the 
test of standing balance, participants are asked to maintain balance in three positions, 
characterized by a progressive narrowing of the base support: with feet together (side-by-
side position), the heel of one foot beside the big toe of the other foot (semi-tandem 
position), and the heel of one foot in front of and touching the toes of the other foot (tandem 
position). For each of the three positions, participants are timed to a maximum of 10 
seconds. Participants are then asked to stand on one leg (on the side of the fracture) with 
eyes open and again with eyes closed. Each of the single leg stands are held for up to 30 
seconds. The number of seconds is then summed across the 5 items to obtain the measure 
of balance. These tests are hierarchical such that when a participant fails an item, the 
harder ones are not administered and receive a score of 0. 
 
Walking speed. Walking speed is assessed by asking participants to walk at their usual 
pace over a 4 m course. Participants are instructed to stand with both feet touching the 
starting line and to start walking after a specific verbal command. Participants are allowed to 
use walking aids (cane, walker, or other walking aid) if necessary, but not the assistance of 
another person. Timing begins as soon as the participant starts to walk and the time in 
seconds needed to complete the entire distance is recorded. The faster of two walks is used 
to compute walking speed. 
 
Chair stands. The repeated chair stands test is performed using a straight-backed chair, 
which is placed with its back against a wall. Participants are first asked to stand once from a 
sitting position with their arms folded across their chest. If they are able to perform the task, 
they are then asked to stand up and sit down five times, as quickly as possible. The time to 
complete the task is recorded. 
 
9.3.3 Activities of Daily Living (ADLs) 
We will measure ADLs using the Pepper Assessment Tool for Disability (PAT-D)145,146 with two 
modifications.  First, two items (walking a quarter mile and walking across a small room) were 
added to address perceived gaps in the original PAT-D scale. This modification is consistent 
with the version used in the Lifestyle Interventions and Independence for Elders study.147  
Second, two items (walking several blocks and lifting heavy objects) were deleted to avoid 
duplication with other items in the scale. The resulting 19-item scale allows examination of three 
subscales (basic ADL, functional limitations, and instrumental ADL).  
 

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9.3.4 Quality of Life (SF-36) 
We will use an interviewer-administered version of the SF-36, a health survey that assesses 
quality of life in eight subscales (physical function, social function, role-physical, role-emotional, 
bodily pain, mental health, general health, and vitality).148  The measure has been validated as a 
generic measure of quality of life in many different populations, including patient and non-patient 
samples.148 61,149,150   
 
9.3.5 Nutritional Status 
Nutritional status will be assessed using the Mini Nutritional Assessment-Short Form (MNA®-
SF),117,151 a validated and widely used malnutrition screening tool.151-154 We are using a modified 
version of the MNA®, approved by the scale’s developer (the Nestlé company), to facilitate use 
as an interviewer-administered tool in a research setting. Scores range from 0 to 14; 
participants scoring ≤7 will be considered malnourished; those scoring 8-11 will be considered 
to be at risk of malnutrition; and those scoring 12-14 will be considered to have normal 
nutritional status.117,151   
 
9.3.6 Muscle and Fat Mass 
Lean mass will be estimated using dual-energy x-ray absorptiometry (DXA) (GE LUNAR, 
Madison, WI). DXA calculates fat and lean tissue mass from the total body scan. The coefficient 
of variation of these measurements in our previous studies for fat and lean mass was 1.4% and 
1.3%, respectively. 
 
9.3.7 Muscle Composition: Intramuscular fat and muscle volume 
Thigh CT will be performed every 4 cm starting at the patella and ending at the femoral head 
(Siemens Somatom Sensation 64 Scanner) to quantify skeletal muscle area, total fat area, low 
density lean tissue area, and muscle attenuation of the thigh. Scans will be analyzed using 
MIPAV (Medical Image Processing, Analysis and Visualization, v.7.0, NIH). The cross-sectional 
area of each axial slice will be multiplied by the distance between slices (4 cm) and summed 
across slices representing volume expressed in cm3. The average attenuation of muscle tissue 
and the percentage of low-density lean muscle to total muscle volume is associated with 
skeletal muscle lipid content, and a measure of muscle quality. 
 
9.3.8 Strength 
A Biodex System 3 PRO dynamometer will measure concentric isokinetic peak normalized joint 
torque over the entire range of motion (strength) for bilateral ankle plantarflexion-dorsiflexion 
and knee flexion-extension. Strength is measured in Newton-meters (Nm). Testing will utilize 
standardized positioning and joint motion excursions. Subjects will perform two blocks of three 
repetitions with a rest period between blocks. 
 
9.3.9  Power 
A Biodex System 3 PRO dynamometer will measure strength per unit of time (power) for 
bilateral ankle plantarflexion-dorsiflexion and knee flexion-extension. Power is measured in 
Watts (W). Testing will utilize standardized positioning and joint motion excursions. Subjects will 
perform two blocks of three repetitions with a rest period between blocks. 
 
9.3.10 Bone Mineral Density 
BMD will be estimated using DXA as described above. DXA of the contralateral (non-fractured) 
femur will be measured to yield measures of total hip and femoral neck BMD. 
 

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9.3.11 Gait and Balance (GAITrite) 
A GAITrite instrumented walkway system will measure spatial and temporal gait parameters. 
Subjects will walk at their safest fast and natural speeds. In addition, the Dynamic Gait Index, a 
clinical assessment of balance and mobility while walking, will be administered. Measures will 
include: step length, walking speed, single and double leg support time, and cadence. 
 
9.3.12 Bone Turnover Markers 
Bone turnover markers. a) bone formation (serum aminoterminal propeptide of type 1 
procollagen; P1NP) and b) bone resorption (serum cross-linked C-telopeptides of type I 
collagen; CTx-I) will be assessed. 
 
9.3.13 Hormones 
Parathyroid hormone, intact (iPTH) will be measured by ELISA. 
 
9.3.14 Inflammatory Cytokines 
a) interleukin-6 (IL-6), b) soluble TNF- α receptor 1 (sTNF- αR1), c) IL-1 receptor antagonist (IL-
1ra), and d) interleukin-10 (IL-10). All cytokines will be measured in serum by ELISA (R&D 
Systems Inc., Minneapolis, MN). 
 
9.3.15 Cognitive Function (Trail Making Test (Trails A and B)) 
The Trail Making Test is a neuropsychological test of visual attention and task switching. It 
consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as 
possible while still maintaining accuracy. The test can provide information about visual search 
speed, scanning, speed of processing, mental flexibility, as well as executive functioning. It is 
sensitive to detecting cognitive impairment associated with dementia. 
 
9.3.16 Waist Circumference 
Waist circumference (cm) reflects adipose tissue distribution and is believed to be influenced by 
glucocorticoid activity. Waist measurement will be taken by measuring tape of the waist 
circumference (narrowest section between the ribs and iliac crest). Waist circumference will be 
measured in centimeters. 
 
9.4 Improvement in Walking 
Whether or not there was an increase of at least 50 meters in the distance walked on the SMWT 
will be assessed as a tertiary outcome. This distance has been shown to be clinically 
meaningful.142,160 
  
9.5 Clinical and Background Characteristics 
Information on a small number of other patient characteristics will be collected to allow 
description of the study population, to allow analyses of differential effects in subgroups (i.e., 
effect modification), and to help in the interpretation of results.   
 
9.5.1 Demographic and Surgical Characteristics 
For descriptive purposes, information on the following participant characteristics will be collected 
either during screening or at the baseline assessment: age, gender, race, living situation, marital 
status, educational level, fracture type, and surgery type. 
 
9.5.2 Functional Comorbidity Index 
The Functional Comorbidity Index (FCI) is a clinically based measure developed by Groll et al.  
This index includes a checklist of 18 comorbid conditions scored 1 or 0. A maximum score of 18 

PUSH Plus Protein Pilot Protocol version3.0 
 
28 
indicates the highest number of comorbid illnesses. The FCI was specifically developed to 
predict physical functioning.161 
 
9.5.3 Weight, Height, and BMI 
Height (in feet and inches) will be measured once at the baseline visit using a standard 
stadiometer. Weight (in pounds) will be measured using a digital scale at baseline and follow-up 
visit.  Measured height and weight will be used to calculate BMI. 
     
9.6  Other Measures to be Monitored 
 
9.6.1 Adherence  
Adherence with PUSH intervention.  PTs will submit a visit form for each of the 32 visits that 
records date of visit; start and end time of the visit; reason for missed visit; what activities were 
performed; and whether activities were performed as prescribed. We will also obtain information 
about the intensity of each activity at initiation of the intervention and every four weeks during 
the intervention period. Logs completed by PTs will record the detail of each designated activity 
during intervention sessions as well as any precautions or modifications to activities. Reasons 
for protocol variations will be noted in the PT log books. 
 
Adherence with protein supplement. We will monitor adherence to the protein supplement by 
weighing the container(s) of protein powder every 4 weeks during the 16-week intervention 
period and by self-report during the 4-week telephone calls. 
 
Adherence with study vitamins/supplements.  Vitamin D, calcium, and multivitamin adherence 
will be monitored by pill counts every four weeks during the intervention period and by self-
report during the 4-week telephone calls for the entire16-week study period. 
 
9.6.2 Weight Loss    
Weight will be monitored by the PTs every four weeks during the 16-week intervention period 
using a standard digital scale.  
 
9.6.3 Reportable Adverse Events (RAEs) 
Reportable adverse events (RAEs), which include serious adverse events (SAEs), unexpected 
AEs or injury that occurs under supervision by study staff, will also be obtained during the study. 
Participants will be screened for possible RAEs every four weeks during the telephone 
interviews using standardized questions.  Participants (or their proxies) will be asked about life-
threatening or significant medical events and the outcomes of these events.  RAEs will also be 
asked about by study staff prior to each PT visit and clinical site follow-up assessment.  RAEs 
may be spontaneously reported to any study staff member throughout the study (see section 
12.4.1).   
 
9.6.4 Expected Adverse Events (AEs) 
Expected AEs will be assessed every four weeks during the telephone interview.  Participants 
(or their proxies) will be asked a series of standardized questions related to pain (feet, hip, back, 
knees, digestive and stomach); breathing problems or chest pain; bloating or puffiness in legs, 
ankles, or feet; drowsiness, dizziness, or confusion; shakiness, anxiety, clammy skin, or 
irritability; and falls (with and without injury).  
 

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29 
Section 10: Study Procedures 
 
10.1 Baseline Assessments 
The baseline assessments will be performed immediately following screening for phase 3 
criteria.   
 
Certain components of the baseline assessment are required by all participants in the pilot study 
in order to make useful comparisons to data from participants in CAP and CAP-MP and to have 
enough power to achieve primary and secondary research aims.  Other assessments at the 
baseline visit will allow comparisons for other outcome measures. Participants who perform the 
required components (marked with a pound sign (#) in the list below) will be eligible to receive 
the PUSH Plus Protein intervention.  All baseline data collection must be completed within 14 
days of the SMWT. 
 
The items with an asterisk (*) are collected as part of phase 3 screening: 
 
▪ 
Baseline Anthropometry #  
▪ 
Demographics and Blood Draw Information # * 
▪ 
Modified Mini-Mental State Examination # * 
▪ 
Six-Minute Walk Test # * 
▪ 
Baseline Interview # 
▪ 
Short Physical Performance Battery #   
▪ 
SF-36 Health Survey # 
▪ 
Pepper Assessment Tool for Disability # 
▪ 
Mini Nutritional Assessment-Short Form # 
▪ 
Trail Making Test (Trails A and B) 
▪ 
Blood draw (for serologic and genetic tests) 
▪ 
Reportable Adverse Events 
▪ 
CT scan of thigh # 
▪ 
DXA scan of whole body # 
▪ 
DXA scan of hip 
▪ 
GAITrite 
▪ 
Four-Square Step Test 
▪ 
Biodex strength testing (knee flexion/extension) 
 
10.2 Follow-up Assessment 
The following measures will be obtained at 16 weeks after baseline testing. 
▪ 
Reportable Adverse Events 
▪ 
Six-Minute Walk Test 
▪ 
Modified Mini-Mental State Examination 
▪ 
Short Physical Performance Battery  
▪ 
SF-36 Health Survey 
▪ 
Weight and waist circumference 
▪ 
Pepper Assessment Tool for Disability 
▪ 
Mini Nutritional Assessment-Short Form 
▪ 
Trail Making Test (Trails A and B) 
▪ 
Blood draw (for serologic and genetic tests) 
▪ 
CT scan of thigh 
▪ 
DXA scans of hip and whole body 
▪ 
GAITrite 

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30 
▪ 
Four-Square Step Test 
▪ 
Biodex strength testing (knee flexion/extension) 
 
10.3 Telephone Interviews 
Structured telephone interviews will be conducted every four weeks for 16 weeks starting four 
weeks after the last date of baseline testing. The following measures will be administered: 
o Reportable Adverse Events (RAE) Form 
o Expected Adverse Events (AE) Form 
o Self-reported adherence to protein and supplements 
 
10.4 Timing of Study Procedures 
The target date for completion of the pre-baseline testing (i.e., screening) assessments will be 
anchored to the date of admission to the hospital for hip fracture. The target date for completion 
of all other assessments will be anchored to the date on which all baseline testing is completed 
(see Table 1).   
 
Note: In cases where the participant performs all required baseline measures and then performs 
additional baseline measures, the date on which baseline testing is completed is defined as the 
date on which the participant performed the last assessment within the allowable window for 
baseline testing (up to 26 week post hospital admission).  In cases where additional baseline 
measures have been scheduled but cannot be completed within the allowable window for 
baseline testing, (e.g., scheduling conflict, not safe), the date on which baseline testing 
completed is defined as the date on which staff establishes definitively that no additional 
baseline measures can or will be attempted.   
 
Table 1. Timing of Study Procedures 
PROCEDURE 
TARGET DATE 
ALLOWABLE INTERVAL 
Phase 3 screening 
As early as possible following 
admission 
Up to 26 weeks post-
admission 
Baseline assessment 
As early as possible following 
admission 
Up to 26 weeks post-
admission 
Dietitian consult 
1 week after baseline testing is 
completed 
+1 week 
First intervention visit 
1 week after baseline testing is 
completed 
+16 weeks 
First telephone interview 
4 weeks after baseline testing is 
completed 
-1 week, +3 weeks  
Subsequent telephone interviews 
At 4-week intervals from date on 
which baseline testing is 
completed 
-1 week, +3 weeks  
First follow-up assessment 
16 weeks after baseline testing is 
completed 
+2 weeks 
Out-of-window assessment 
16 weeks after baseline testing is 
completed 
0-16 weeks and 18-38 
weeks after baseline 
testing is completed 
 
At baseline, all participants will, by design, be tested at the clinical site. At the follow-up visit, we 
will attempt to test all participants at the clinical site. When this is not possible, we will attempt to 
have study staff administer the test in a non-study clinical facility or, failing that, at another non-
study location or the participant’s home.  

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31 
 
Section 11: Safety Assessments 
11.1 Participant Safety Parameters: Methods and Timing  
11.1.1 Pre-Intervention Safety Screening 
Potential participants will be excluded during the screening phases if they have cardiovascular 
diseases or other conditions that would make it unsafe for them to participate in one or both of 
the study interventions. Information about these conditions will be obtained through chart 
review, interviews, and consultation with a medical professional familiar with the potential 
participant (e.g., primary care provider, orthopaedic surgeon). The study physician and PI will be 
responsible for giving permission for potential participants to receive the intervention, based on 
thorough review of all eligibility information. In addition, persons who develop chest pain or 
substantial shortness of breath during the SMWT will be excluded using a protocol to evaluate 
cardiovascular reserve similar to the one suggested by Gill et al.162  
  
11.1.2 Safety Considerations for Study Assessments 
All study assessments will be done by certified staff who will be trained to perform the tests 
safely. If, during the SMWT or the SPPB a participant reports chest pain, tightness or pressure, 
significant shortness of breath or difficulty breathing, or feeling faint, lightheaded, or dizzy, the 
test will be stopped. If the participant weighs more than 400 pounds or if s/he is unable to lie 
supine, the whole body and hip DXA scans will not be done. Participants with prior hardware in 
the non-fractured hip will not have a hip DXA scan.  If a participant is unable to lie supine or be 
left alone in a room, the thigh CT scan will not be done. Participants unable to put full weight on 
the fractured side or unable to stand for 30 seconds without an assistive device will not perform 
the GAITrite or Biodex measures. All research staff who come in contact with study participants 
will be CPR certified and will be trained to provide immediate care when faced with medical 
emergencies. Also, institutional and community emergency medical services will be activated if 
needed.  
 
Table 2 describes a summary of safety alerts and the appropriate action during clinical 
assessments. 
 
Table 2. Safety Alerts and Actions for Study Assessments 
ALERT 
ACTION 
Resting blood pressure 
SBP > 145mm Hg or 
DBP > 90mm Hg 
Qualified staff will inform the participant if 
noted on more than one occasion. 
Resting blood pressure 
SBP > 170mm Hg or SBP < 90mm Hg or 
DBP > 100mm Hg or DBP < 50mm Hg 
Qualified staff will encourage the participant 
to seek additional follow-up and/or medical 
evaluation.  Physical performance testing 
will be deferred until consultation with the 
study physician. 
Resting blood pressure or after SMWT 
SBP > 185mm Hg or SBP < 90mm Hg or 
DBP > 110mm Hg or DBP < 50mm Hg 
Qualified staff will consult with the study 
physician and follow up as needed.  
Resting pulse 
Rate > 120 or < 40 beats/min 
Qualified staff will consult with the study 
physician and follow up as needed.  

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32 
Table 2. Safety Alerts and Actions for Study Assessments 
Chest pain, dizziness, significant shortness 
of breath, or severe musculoskeletal pain 
during the intervention or study 
assessment. 
Qualified staff will consult with the study 
physician and follow up as needed.  
MNA®-SF  
Score ≤ 7 at the follow-up assessment 
Qualified staff will talk to the participant and 
provide a referral for additional follow-up 
and/or medical evaluation for possible 
malnutrition.       
Weight loss ≥ 2% body weight in four 
weeks during intervention period 
Participant will be referred to the registered 
dietician for follow-up by telephone. 
Participant expresses desire to commit 
suicide 
Call primary care provider and report 
findings. Report to study coordinator/study 
physician for follow-up and clearance. 
 
11.1.3 Safety Considerations for the PUSH Intervention 
There is no expectation that the PUSH intervention will evoke serious cardiovascular responses; 
however, participants will be warned of a possible risk. Cardiac events are rare, with estimates 
of one event per 60,000 participant-hours in aerobic exercise programs.163  No significant 
cardiac events were reported after performing 1-RM testing for over 6600 healthy subjects.164 
The American Heart Association’s guidelines for resistance training for adults with and without 
cardiovascular disease reports the safety of high intensity resistance training and testing in 
persons with coronary disease which found an absence of anginal symptoms, ischemic ST-
segment depression, abnormal hemodynamics, complex ventricular dysrhythmias, and 
cardiovascular complications.165,166 Less serious risks may include chest pain, fainting, 
hypotension, or muscle strain. We have minimized risk to participants by following the 
guidelines suggested by Gill et al.162  Blood pressure and heart rate will be monitored using a 
standard blood pressure cuff and palpation of peripheral pulse. 
 
Another concern is the presence of osteoporosis and the risk of inducing a compression fracture 
or a lower extremity fracture. The exercises have been designed to minimize this risk. The risk 
of inducing a compression fracture will be minimized because the exercises are performed in 
supine and upright standing positions with minimal to no trunk flexion.167 The PT will also remind 
the participant to minimize flexion to the spine during all standing exercises. Using an exercise 
device that eliminates the risk of weights falling on a person, and using only voluntary muscle 
contractions during isometric testing, will reduce the risk of lower extremity fracture. We do not 
anticipate additional risk for the PUSH intervention for the following reasons: 1) by 12 weeks 
post-fracture, there is moderate stability from the bone callus formation, 2) participants will only 
be included if they have medical clearance to participate in full weight bearing activities, and 3) 
the device limit is 100 pounds (which in most cases is less than body weight) resulting in less 
load than walking up and down stairs. Delayed onset muscle soreness is a common occurrence 
after the initiation of an exercise program. The soreness occurs in the muscle belly 1-3 days 
after the initiation of exercise and lasts 2-3 days. There is no effective way to eliminate the risk 
of delayed onset muscle soreness, but it is hoped that the orientation process and gradual 
increase in intensity will reduce the risk. The participants will be informed about the condition, 
what it feels like, how long it lasts, and suggested ways of decreasing the pain including the use 
of superficial heat or ice. If a participant reports continued discomfort, the study physician will 
discuss this with the participant and contact their primary care provider (PCP) as necessary. 
Please see Table 3 below for a summary of alerts and appropriate action during the PT 
intervention visits. 
 

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33 
11.1.4 Safety Measures during the PUSH Intervention 
The PUSH intervention will be conducted in the participant’s place of residence and all sessions 
will be conducted and supervised by trained PTs, who monitor potential adverse experiences 
and symptoms. PTs will be trained to deal with medical emergencies that occur during the 
PUSH sessions and will be CPR certified. Also, community EMS services will be activated if 
needed.  
 
In order to minimize discomfort and maximize safety, participants will be taught the proper 
method for performing each exercise and the importance of following the proper method. 
Intensity is gradually increased, and exercise technique is commented on during each session. 
Participants will be instructed to talk with the PTs about any muscle soreness, pain or 
discomfort. 
 
Every effort will be made to prevent harm by stopping intervention activity when the participant 
reports chest pain, dizziness, significant shortness of breath, or severe musculoskeletal pain.  
PTs will monitor blood pressure at the start of the training session, mid-session, and when 
participants are finished with the session. Blood pressure and heart rate will be monitored using 
a standard blood pressure cuff and palpation of peripheral pulse. If blood pressure is elevated 
above 170/100, the participant will rest quietly for a few minutes. The PT will monitor the 
participant for signs of muscle strain, dizziness, or hypotension and appropriate palliative 
methods will be discussed with the participants and appropriate medical referrals will be made.  
Please see Table 3 for a summary of alerts and appropriate action during the PT intervention 
visits. 
 
11.1.5 Safety Considerations for the Protein Intervention 
Although the protein supplement used in this study is virtually lactose (sugar) free, small 
amounts of lactose may trigger digestive upset (abdominal pain, gas, and diarrhea) for 
participants who suffer from lactose intolerance. Although this product may not contain one or 
all of the following, this product is manufactured in a facility that handles milk, soy, egg, peanut, 
nut, tree, fish, crustaceans/shellfish, and wheat products.  Those who have celiac disease or 
who have a known allergy to dairy, peanuts, or shellfish are excluded from participation. Whey 
provides no fiber to the diet, and excessive consumption may lead participants to experience 
constipation unless they consume high-fiber foods in addition to whey. There is an extremely 
low risk of renal (kidney) or liver damage related to whey protein supplementation. Those with a 
history of severe liver disease (e.g., hepatitis, fatty liver disease, cirrhosis), chronic kidney 
disease (CKD stage 4), or a calculated creatinine clearance 15-29 ml/min are excluded from 
participation. There is an extremely low risk that participants with poorly controlled type 2 
diabetes could experience hypoglycemia (low blood sugar). Those with hemoglobin A1c level 
greater than 10% are excluded from participation. Please see Table 3 for a summary of alerts 
and appropriate action for the protein intervention. 
 
Table 3. Safety Alerts and Actions for Interventions 

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34 
ALERT 
ACTION 
Resting blood pressure 
SBP > 170mm Hg or SBP < 90mm Hg or 
DBP > 100mm Hg or DBP < 50mm Hg 
1. If initial BP check is high (systolic > 170; 
diastolic >100), have participant sit for 5 
minutes and rest then check BP again. 
This may be done twice. 
2. If three BP readings are greater than 
170/100, then individual should not 
exercise.  
3. The PCP, study coordinator, and study 
physician should be called before 
exercise is initiated.   
4. If initial BP is low for that person 
(systolic<90; diastolic<50) follow same 
protocol.   
New chest pain 
 
Reported chest pain that occurred between 
visits 
Call 911. 
 
1. Cancel treatment and call PCP. 
2. Report to study coordinator and study 
physician to follow-up until cleared. 
Acute shortness of breath 
1. Have participant stop exercising and 
rest. 
2. Take vital signs. 
3. If the shortness of breath does not 
resolve itself in 10 minutes, and vital 
signs are not within normal limits for 
participant, call 911.   
4. Report to PCP, study coordinator, and 
study physician.  
Fall 
 
1. If there is bleeding/wound, apply 
pressure using emergency kit for wound; 
call 911 if needed.  If participant is  
unable to stand or move the injured part, 
call 911 and keep them warm and 
comfortable. 
2. Report all falls to study coordinator.  
3. Complete an incident report.   
Stroke symptoms 
Call 911 immediately. 
Dizziness during exercise 
1. Stop exercise and have person sit or lie 
down. 
2. If sitting is not sufficient to resolve 
dizziness, then check vital signs.   
3. Call 911 if clinically unstable. 
4. Report to PCP if heart rate is less than 
60 (and not usually so), the dizziness is 
new in onset; or if the BP is > 160/100 or 
systolic <90.   
5. Report event to study coordinator and 
study physician.         

PUSH Plus Protein Pilot Protocol version3.0 
 
35 
ALERT 
ACTION 
Resting pulse 
Rate > 120 or < 40 beats/min 
1. PT will stop delivery of the intervention.  
2. Qualified staff will consult with the study 
physician and follow up as needed.  
3. PT will resume delivery of the 
intervention only after the participant 
receives medical clearance.   
New irregular heart rate with complaint of 
heart palpitations 
1. Do not exercise and call PCP. 
2. Report to study coordinator and study 
physician for follow-up. 
3. Wait for medical clearance to resume 
exercise. 
New acute musculoskeletal pain during 
exercise (pain > 5 on VAS) 
1. Have the participant stop the exercise 
and rest.  
2. Attempt to alter position of participant to 
reduce pain. If pain persists, do not 
continue specific exercise. Attempt to do 
other exercises.  
3. If pain does not resolve, refer to PCP or 
orthopedist and study physician. 
New, acute, non-musculoskeletal pain  
(pain > 5 on VAS) 
1. Do not exercise. 
2. Take pain history and call PCP. 
3. Report to study coordinator and study 
physician for follow-up and clearance. 
Acute change in mental status 
1. Do not exercise. 
2. Call PCP or if unavailable, call 911. 
3. Report to study coordinator and study 
physician for follow-up and clearance. 
Participant expresses desire to commit 
suicide 
1. Call PCP and report findings. 
2. Report to study coordinator and study 
physician for follow-up and clearance. 
Participant exhibits signs of allergic 
reaction to protein. 
1. Do not give protein supplement. 
2. Call PCP and report findings. 
3. Report to study coordinator and study 
physician for follow-up and clearance. 
 
11.1.6 Safety Measures for the Protein Intervention 
In order to minimize discomfort and maximize safety, PTs will instruct participants on how to 
take the protein supplement.  We will monitor for potential adverse events.  A participant who 
exhibits signs of allergic reaction to the protein will stop receiving the protein supplement and 
the study physician and PCP will be consulted.   
 
11.1.7 Safety Considerations for Nutritional Support 
Individuals who have sustained a hip fracture are frequently at risk for protein and calorie 
malnutrition and have low calcium and vitamin D intake.168  Individuals enrolled in the study will 
be screened with the MNA®-SF and if their scores indicate that they are malnourished, they will 
receive in-person nutritional counseling by a registered dietician.  Individuals enrolled that have 
a serum albumin value 2.5-3.5 will also receive in-person nutritional counseling by a registered 
dietician, regardless of score on the MNA®-SF. Participants who are at risk or not at risk for 
malnutrition will receive a telephone consultation from the dietician on maintaining proper diet. 

PUSH Plus Protein Pilot Protocol version3.0 
 
36 
The RD will schedule an in-person visit for those at risk if he/she feels it is necessary based on 
the telephone consultation. All subjects will receive vitamin D, calcium, and multivitamin 
supplementation for the 16-week study period, all of which represent best practices for this 
disabled group of participants.  There are small risks associated with vitamin D, calcium, and 
multivitamins including gastrointestinal complaints (including mild constipation or diarrhea, 
stomach upset) and kidney stones.  Those with a calculated creatinine clearance less than 30 
ml/min, elevated total or ionized calcium, or history of kidney stones, primary 
hyperparathyroidism, or sarcoidosis will not receive calcium supplements. A participant who 
experiences an episode of kidney stones during the study period will stop receiving calcium 
supplements.  
 
11.1.8 Safety Measures for Nutritional Support 
If a participant loses 2% or more body weight in a four-week period, the participant will be 
referred to the registered dietician for follow-up by telephone.   
11.2 Confidentiality  
Confidentiality of data will be maintained by using research identification numbers and letter 
codes that uniquely identify each individual. Safeguards will be established to ensure the 
security and privacy of participants’ study records. Data will be stored in locked files and on 
computer disks, with access limited to the investigators and key study personnel. Computer 
data files will not include participant names, addresses, initials, hospital record number, or any 
other personal identifiers. Computer security procedures, including multiple levels of password 
protection will be instituted. Data for publication will be presented only in aggregate form, 
preventing identification of individual participants. After the study is completed, local data will be 
archived in a secured storage area.  
 
In compliance with the Health Insurance Portability and Accountability Act (HIPAA) and the 
Standards for Privacy of Individually Identifiable Health Information of the Department of Health 
and Human Services, CAP will access personal health information and medical records only 
after receiving approval for a HIPAA Partial Privacy Waiver for Recruitment.  Only information 
necessary for determining eligibility will be obtained.  
11.3 Participant Education about Potential Risks 
Potential risks associated with study-related activities and interventions will be explained to 
each participant by trained study personnel during the informed consent process. Each 
participant will be instructed to report the occurrence of an AE to appropriate study staff at 
scheduled data collection times, to PTs administering the intervention, or spontaneously at any 
other time. Participants also will be encouraged to report concerns about the safety of 
participating in the study.  
 
 
Section 12: Reportable Adverse Events (RAEs) and Expected Adverse 
Events (AEs) 
 
12.1 Overview 
In this study we will capture study-defined expected adverse events (AEs) through structured 
telephone interviews every four weeks. Reportable AEs (RAEs) are defined as serious adverse 
events (SAEs), AEs that have potential implications for participant safety, unexpected AEs, and 
injury that occurs while a participant is under the supervision of study related personnel. These 

PUSH Plus Protein Pilot Protocol version3.0 
 
37 
RAEs will require individual event reporting as described in section 12.4.  The timely and 
complete account of RAEs will be a critical requirement for the protection of human subjects in 
this study.     
 
The University of Maryland Claude D. Pepper Older American Independence Center (UM-OAIC) 
DSMB will review and approve study-defined expected AEs and will be involved in regular 
monitoring of the RAE reporting system.   
 
12.2 Classifying Adverse Events 
An AE is any unfavorable or unintended medical occurrence in a human study participant that 
has taken place during the course of a research project, including any abnormal sign, symptom, 
or disease, whether or not related to participation in the research   
 
For the purposes of this study, any event that meets the criteria for an SAE, is unexpected, or 
results in injury to the participant while s/he is under the supervision of study related personnel 
will be classified as an RAE.   
 
Adequate review, assessment, and monitoring of RAEs require that they be classified as to 
severity, expectedness, and potential relatedness to the study intervention.   
 
12.2.1 Severity  
The study physician will use the following guidelines to determine level of severity: 
 
Mild: Awareness of signs or symptoms, but easily tolerated and causing no loss of time from 
normal activities. No specific medical intervention is required. 
 
Moderate: Discomfort enough to cause a low level of inconvenience or concern to the 
participant and may interfere with daily activities. Symptoms may require minimal, local, or 
noninvasive medical intervention only. 
 
Severe:  Events interrupt the participant’s normal daily activities and are usually incapacitating. 
Significant symptoms may require hospitalization or invasive medical intervention.  
 
Life threatening: Events that may involve acute, life-threatening metabolic or cardiovascular 
complications (such as circulatory failure, hemorrhage, sepsis) or life-threatening physiological 
consequences. Intensive care or emergent invasive procedure is required. 
 
Fatal: Causing death. 
 
Severity is not synonymous with seriousness. A severe headache is not necessarily an RAE.  
However, mild chest pain may result in a day’s hospitalization and thus would be classified as 
an RAE. 
 
12.2.2 Expectedness  
An independent safety monitor (ISM) will assess AEs as to whether they were expected or 
unexpected based on current knowledge. Categories are: 
 
Expected: An AE that is anticipated on the basis of prior experience with the intervention under 
investigation; an event that can be attributed to the underlying condition of the participant being 

PUSH Plus Protein Pilot Protocol version3.0 
 
38 
studied; or an event that can be attributed to the patient population being studied (see section 
12.3). Expected AEs are captured in a standardized way every four weeks. 
 
Unexpected: An AE that was not anticipated on the basis of prior experience with the 
intervention under investigation; an event that cannot be attributed to the underlying condition of 
the participant being studied or to the patient population; or an expected event whose frequency 
or severity exceeds what was anticipated (see section 12.4.2).  Unexpected AEs are reportable. 
 
12.2.3 Relatedness   
The ISM will determine the degree to which RAEs are related to study procedures.  
 
Definitely related: The adverse event is clearly related to the investigational procedure – i.e., an 
event that follows a reasonable temporal sequence from administration of the study intervention, 
follows a known or expected pattern of response to the study intervention, that is confirmed by 
improvement on stopping and reappearance of the event on repeated exposure, and that could 
not be reasonably explained by the known characteristics of the participant’s clinical state. 
 
Possibly related:  An adverse event that follows a reasonable temporal sequence from 
administration of the study intervention or that follows a known or expected pattern of response 
to the study intervention, but that could readily have been produced by a number of other 
factors. 
 
Not related:  The adverse event is clearly not related to the investigational procedure (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 and the study intervention and/or a causal relationship is 
considered biologically implausible).      
 
12.3 Expected AEs 
Expected AEs will be captured through telephone interviews every four using the Expected 
Adverse Events Form. Following are expected adverse events that have been listed in the ICF:   
• 
foot pain  
• 
hip pain  
• 
back pain  
• 
knee pain  
• 
digestive or stomach pain 
• 
breathing problems 
• 
chest pain or discomfort 
• 
bloating or puffiness in the legs, ankles, or feet 
• 
drowsiness, dizziness, or confusion 
• 
shakiness, anxiety, clammy skin, or irritability 
• 
fall (with or without injury) 
 
12.4 Reportable AEs 
RAEs are events that have potential implications for participant safety and that require individual 
reporting.  RAEs will be defined as events that fall into at least one of the following categories: 
1. Serious adverse events (SAEs) 
2. Unexpected AEs, and 
3. Injury that occurs while a participant is under the supervision of study personnel. 
 

PUSH Plus Protein Pilot Protocol version3.0 
 
39 
Events that cannot be clearly defined as “reportable” will be discussed with the study physician 
and PI to determine if they should be reported. 
 
12.4.1 Serious Adverse Event (SAE)  
SAEs will be defined as any event that: 
• 
Results in death 
• 
Is life threatening, or places the participant at immediate risk of death (e.g., MI, 
stroke/TIA) 
• 
Requires or prolongs hospitalization 
• 
Causes significant disability or incapacity (e.g., torn muscle or ligament) 
• 
Requires medical or surgical intervention to prevent significant disability (e.g., hip 
fracture) 
 
SAEs will be assessed through telephone interviews every four weeks using the Reportable 
Adverse Events Telephone Screening Form.  SAEs will also be assessed at the beginning of 
each PT visit and clinical site visit, and by any study staff who learns of a serious event. 
 
12.4.2 Unexpected Adverse Event  
Unexpected AEs will be defined as medical events that occur during study participation, but do 
not commonly occur in the study population and which are not listed in the ICF or study protocol 
(section 12.3).  An unexpected AE may be witnessed by a member of the research team, or 
staff may be told about an unexpected event that may meet the criteria for reporting. 
Unexpected AEs that have a potential relationship to study procedures and activities will be 
captured on an Incident Report and submitted to the study office where they will be logged in 
the participant binder and then reported to the Independent Safety Monitor (ISM).   
 
A reportable unexpected AE will be one that meets all of the following criteria: 
• 
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 ICF; and (b) the characteristics of the study 
population;  
• 
Related or possibly related to participation in the research (meaning that there is a 
reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research);  
• 
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. 
 
The medical and scientific judgment of the study physician and the PI will be exercised in 
deciding whether an occurrence should be reported. In addition, difficulty determining whether 
or not an event is unexpected and/or attributable to the intervention will be addressed by the 
ISM, who will determine if the event is to be reported. 
 
12.4.3 Injury that Occurs while Under the Supervision of Study Related Personnel 
Any injury that occurs while the participant is under the supervision of study-related personnel is 
reportable.  The injury can happen on site (during an assessment visit) or off-site (in the 
participant’s home during a PT visit or if the study offers supervision during transportation).  
These events will be captured on the Reportable Adverse Events Form.   
 

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40 
12.5 Expected AE and RAE Collection and Reporting 
The requirements for reporting RAEs will begin when the participant provides informed consent 
and will end 30 days after the participant’s involvement in the study has ended. Expected AEs 
will be assessed every four weeks after baseline testing.  Figures 5a-d provide algorithms 
describing the reporting process. 
 
 
Figure 5a. Collection and Reporting Process for Expected AEs 
Evaluator administers the Expected Adverse Event Form at a scheduled 4-week telephone interview 
Non-serious and expected AE is reported by the participant or proxy 
Evaluator submits the Expected AE form to the study office 
THE PI (OR DESIGNEE) SUBMITS EXPECTED AES 
WITH THE ROUTINE DSMB REPORT SEMI-ANNUALLY 
STOP 
Evaluator
PI (or designee) 
LEGEND 

PUSH Plus Protein Pilot Protocol version3.0 
 
41 
 
Has the RAE been previously reported? 
Figure 5b. Collection and Reporting Process for RAEs Collected during Standardized Telephone 
Interviews 
Evaluator administers the Reportable Adverse Events Telephone Screening 
Form at a scheduled 4-week telephone interview 
Evaluator completes the Adverse Event Narrative and Reportable Adverse Event Form PA for each 
event and submits documentation to the study coordinator 
Study coordinator records RAE ID#, marks 
as duplicate, and files in participant binder 
YES 
Study coordinator assigns new RAE ID#, and records 
event on the RAE Log in the participant binder 
PI (or designee) redacts documents to conceal PHI  
Event is identified by the participant or proxy & meets the criteria for an RAE 
Study coordinator completes RAE 
Record and notifies PI and study 
physician immediately 
NO 
PI (OR DESIGNEE) 
NOTIFIES THE UM-OAIC 
PROGRAM DIRECTOR  IN 
WRITING WITHIN 24 
BUSINESS HOURS OF THE 
PI BECOMING AWARE OF 
THE EVENT  
Study Coordinator 
Evaluator 
LEGEND 
PI (or designee) 
Does the event meet criteria for 
immediate reporting to the DSMB? 
NO 
YES 
PI (OR DESIGNEE) 
REPORTS THE EVENT 
TO THE UMB IRB 
VIA THE CICERO 
REPORTING SYSTEM 
WITHIN FIVE DAYS 
THE EVENT WILL BE INCLUDED 
IN THE SUMMARY OF ALL 
OTHER RAES SUBMITTED TO 
THE UM-OAIC DIRECTOR, 
DSMB, AND NIA PROGRAM 
OFFICIAL IN ROUTINE DATA 
AND SAFETY REPORTS  

PUSH Plus Protein Pilot Protocol version3.0 
 
42 
 
 
Staff is told about an event that meets the criteria for an RAE  
Staff completes an Adverse Event Narrative and Reportable Adverse Events Form PA and submits 
documentation to the study coordinator 
Staff witnesses a serious or unexpected event 
that meets the criteria for an RAE  
Figure 5c. Collection and Reporting Process for RAEs Identified Anytime Other than During a 
Standardized Telephone Interview 
Study Coordinator 
Study Staff 
LEGEND 
PI (or designee) 
Has the RAE been previously reported? 
Study coordinator records RAE ID#, marks 
as duplicate, and files in participant binder 
YES 
Study coordinator assigns new RAE ID#, and records 
event on the RAE Log in the participant binder 
Study coordinator completes RAE 
Record and notifies PI and study 
physician immediately 
NO 
Does the event meet criteria for 
immediate reporting to the DSMB? 
NO 
YES 
PI (OR DESIGNEE) 
REPORTS THE EVENT 
TO THE UMB IRB 
VIA THE CICERO 
REPORTING SYSTEM 
WITHIN FIVE DAYS 
THE EVENT WILL BE INCLUDED 
IN THE SUMMARY OF ALL 
OTHER RAES SUBMITTED TO 
THE UM-OAIC DIRECTOR, 
DSMB, AND NIA PROGRAM 
OFFICIAL IN ROUTINE DATA 
AND SAFETY REPORTS  
PI (or designee) redacts documents to conceal PHI  
PI (OR DESIGNEE) 
NOTIFIES THE UM-OAIC 
PROGRAM DIRECTOR  IN 
WRITING WITHIN 24 
BUSINESS HOURS OF 
THE PI BECOMING 
AWARE OF THE EVENT  

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43 
Figure 5d. Review and Reporting Process for RAEs 
Study coordinator records information on RAEs in the RAE tracking database 
Study coordinator forwards redacted RAE documents to the ISM on call to confirm appropriate classification 
PI (OR DESIGNEE) NOTIFIES THE UM-OAIC 
PROGRAM DIRECTOR IN WRITING WITHIN 24 
BUSINESS HOURS OF THE PI BECOMING 
AWARE OF THE EVENT  
Is this event a 
participant death or 
an injury that 
occurred while a 
participant is under 
study supervision? 
ISM notifies study 
coordinator that 
additional 
information is 
needed to make a 
clear determination 
Study coordinator gathers 
additional information and 
sends to ISM 
YES 
NO 
UNCLEAR 
YES 
ISM updates the RAE 
Evaluation report and 
submits RAE Follow-
up forms to the study 
coordinator as new 
information becomes 
available 
ISM confirms final status as determined by the study 
clinician and submits a Final Status form to the study 
coordinator to close out the event 
PI (OR DESIGNEE) SUBMITS A TABLE SHOWING ALL RAES WITH THE ROUTINE DSMB REPORT SEMI-ANNUALLY 
Is this RAE ongoing? 
STOP 
NO 
Site Coordinator 
ISM 
LEGEND 
PI (or designee) 
RAEs are coded using MedDRA 
Is this event 
unexpected and 
related or possibly 
related to the study 
and suggest that 
the research places 
participants or 
others at a greater 
risk of harm? 
YES 
PI (OR DESIGNEE) 
REPORTS THE EVENT 
TO THE UMB IRB 
VIA THE CICERO 
REPORTING SYSTEM 
WITHIN FIVE DAYS 

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44 
Timeline for Reporting Events 
The RAE reporting schedule is shown below: 
1. Staff will report RAEs to the PI and study physician as soon as the event is known and 
submit documentation of the event to the study coordinator in real time. 
2. All injuries that occur while a participant is under the supervision of study personnel and 
all participant deaths (regardless of relatedness) will be reported to the OAIC Program 
Director within 24 business hours (excluding weekends and holidays) of the PI becoming 
aware of the event.  
3. Events that are reviewed by the ISM and subsequently classified as related or possibly 
related to the research will also be submitted to the OAIC Program Director. 
4. All other RAEs, SAEs, expected AEs, and protocol deviations will be requested 
semiannually by the OAIC to be presented to the DSMB. 
 
12.6 Evaluation and Follow-up of RAEs 
All RAEs will be forwarded to an ISM for adjudication and follow-up.  The ISM may contact the 
study coordinator to request additional information from the participant, significant other, or their 
health care provider and may seek medical records from a physician or care setting if needed to 
make a determination about relatedness to the study.  If the event is potentially related to the 
study, the ISM will consider whether the event was listed in the protocol and ICF and whether 
modifications to the protocol and ICF should be considered. To ensure the appropriate 
classification of events, the study physician and/or PI may also be called on to provide 
additional information. 
 
The ISM will be responsible for providing follow-up for ongoing reportable events, as follows: 
 
1. The ISM will make a determination about relatedness and expectedness of the event and 
submit a Reportable Adverse Event Evaluation to the study coordinator.   
2. If there are follow-ups to an event (and the event is ongoing), the ISM will complete the RAE 
Follow-up Form to record any updates and submit to the study coordinator.  
3. The ISM will follow up on RAEs until a final status has been determined for the event (e.g., 
recovered, ended in death, is still present, or status is unknown). Some RAEs may have a 
status of still present at the conclusion of the study. These are the categories of RAE status:  
a. ‘Resolved’ is an event that has ended, with or without residual deficits. 
b. ‘Still present’ is an event that is ongoing.  
c. ‘Unknown’ should be used when the site is unable to make contact with the 
participant or proxy or to obtain additional information in any other way. 
d. ‘Died’ is for an event that ended in death. 
4. Once the event is no longer ongoing and a final status for the event has been determined by 
the study physician, the ISM will confirm the final status, record the closed date, and sign and 
date the RAE Final Status Form that will be submitted to the study coordinator. 
 
12.6.1 Action Taken 
The PI, in consultation with the study physician and the ISM, will decide whether or not an RAE 
requires that the participant be removed from the study intervention. The UM-OAIC DSMB will 
be notified of the recommended course of action by the PI in the routine DSMB report.  Actions 
taken in response to the RAE will fall into one of five categories: 
• 
Study intervention modified 
• 
Study intervention suspended temporarily 
• 
Study intervention stopped permanently 
• Study assessment modified 
• No action taken 

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45 
12.7 Responsibilities 
The PI has primary responsibility for the safety of participants as it relates to the study protocol.  
The study coordinator will be responsible for reviewing RAEs and assuring accurate and timely 
reporting of RAEs.  The study physician will be responsible for reviewing RAEs.   ISMs will 
evaluate and classify RAEs and provide follow-up for events until they are resolved. The UM-
OAIC DSMB will be responsible for reviewing monitoring data for evidence of harm attributable 
to participation in the study. 
 
12.7.1 Study Physician 
The study physician will be responsible for being “on call” for study-related emergencies and will 
be available by telephone for consultation with study personnel during all time periods when 
participants are engaged in the home-based interventions or at clinical assessment visits. In 
addition, the study physician will be responsible for reviewing RAEs requiring immediate 
notification to the UM-OAIC DSMB and NIA.  The study physician will assess severity and 
consider whether participation in the study should change for reasons related to safety.  The 
physician will also make a determination about final status once the event has resolved.  
 
The study physician may delegate responsibilities related to immediate notification to a 
“covering” physician who has been trained on the protocol. 
 
12.7.2 Independent Safety Monitor (ISM) 
Physicians will serve as ISMs to review RAEs on a rotating basis. When a RAE is identified the 
information will be redacted to conceal PHI and then forwarded to the on-call ISM to make a 
determination.  The ISM will be responsible for: 
 
• 
reviewing reports of RAEs;  
• 
confirming or refuting classification of the event as an RAE; 
• 
evaluating the expectedness of the RAE; 
• 
making a determination about relatedness of the RAE; 
• 
requesting additional information as needed in order to make a determination;  
• 
providing the study coordinator with follow-up reports for ongoing RAEs as new 
information becomes available; 
• 
confirming the final status for the event once it has been determined by the study 
physician; and 
• 
submitting a final status report to the study coordinator. 
 
12.8 Reporting Expected AEs and RAEs to the UM-OAIC DSMB 
The UM-OAIC DSMB will review tabulated data on non-serious and expected AEs on a semi-
annual basis and monitor for adverse event rates out of proportion to those expected. The PI (or 
designee) will forward the individual Reportable Adverse Event Record and AE Narrative for 
each event requiring immediate notification to the UM-OAIC DSMB and NIA as well as a table 
showing all RAEs to the UM-OAIC DSMB and NIA semi-annually. The UM-OAIC DSMB will 
review all RAEs that are temporally related to the intervention in aggregate form at its scheduled 
meetings. 
 
All RAEs that relate to hazards of the study intervention or are cause for urgent concern will be 
reported to the UM-OAIC DSMB chair, NIA, and the UMB IRB immediately after recognition of 
their importance. The DSMB chair may conclude that an RAE is of universal and immediate 
concern. The DSMB chair may also recommend convening the UM-OAIC DSMB to review 
participant safety based on any individual report or accumulating evidence.  

PUSH Plus Protein Pilot Protocol version3.0 
 
46 
 
Section 13: Intervention Discontinuation 
Certain RAEs may result in a temporary interruption or early discontinuation of the trial 
assessments and interventions or components of these assessments and interventions. Please 
refer to the appropriate MOP chapter(s) for specific instructions on stopping criteria during 
screening, intervention, and follow-up assessments.  
 
After such RAEs occur, a participant may resume the trial intervention when the study physician 
and the primary care provider (if participant has one) agree that it is appropriate. For mild 
problems that require temporary cessation of intervention, the PI, in consultation with the study 
physician and participant, may agree to reintroduce the participant to the study intervention.  
 
At any time, the UM-OAIC DSMB may recommend discontinuation of any component or 
intervention group of the study for any of the following reasons: 
1)  Compelling evidence from this or any other study of an adverse effect of the 
study intervention(s) that is sufficient to override any potential benefit of the 
interventions to the target population. 
2)  Compelling evidence from this or any other study of a significant beneficial effect 
of the study intervention(s), such that its continued denial to other study group(s) 
would be unethical. 
3)  A very low probability of addressing the study goals within a feasible time frame. 
 
Section 14: Data Analyses 
 
14.1 Primary Aim 
The primary aim is to compare the PUSH Plus Protein study subjects (n=30) to those who 
received PUSH from CAP (n=105). The primary outcome is the distance walked in six minutes 
(6MWT). Previous analyses of various physiologic measures in the Baltimore Hip Studies data 
(“BHS”; data unpublished) have shown a r>0.80 within subject correlation of measures across 
time. Preliminary data from CAP-MP have shown a within subject correlation of r=0.78 for initial 
subjects in usual walking speed (n=13).  
 
14.2 Secondary Objectives 
 
A longitudinal analysis using Generalized Estimating Equations (GEEs) will be employed. A 
model of the form Y(t) = a + b1 X + b2 t4 + b3 Xt4 will be used where: Y(t) is the dependent 
variable Y at time t (which is 0 or 4 months post baseline testing); a is the intercept; X is an 
indicator variable for treatment group (PUSH vs PUSH+ Protein); t4 is an indicator variable for 
time at 4 months post baseline testing; Xt4 is an interaction term for treatment and time; and b1 
through b3 are empirically derived regression coefficients. An unstructured covariance matrix, 
an identity link function, and robust standard errors will be used. The effect of intervention on 
each mechanistic factor will be assessed by estimating the magnitude of the coefficient b3, 
which is interpreted as mean change in outcome from baseline to 4 months comparing PUSH 
Plus Protein to PUSH alone.  The primary outcome will be the 6-minute walk test (6MWT).  
Other potential outcomes include: activities of daily living (ADLs), quality of life, lower-extremity 
physical performance, increase of ≥ 50 meters in distance walked in six minutes, cognitive 
status, and nutritional status. 
 

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47 
14.3 Missing Data 
By design, there will be no missing data at baseline because only participants with complete 
baseline data will be randomized. At follow-up, scores for scales that have published rules for 
handling missing scale items (e.g., the CES-D and the SF-36) will be calculated using those 
rules. All other scales will be considered missing if any part of the scale is missing. To correct 
for potential selection bias from missing data, we will perform a weighted estimating equations 
(WEE) analysis.169 This method involves two steps. First the probability of being observed (not 
missing) is calculated as a function of predictors of missingness. Next the relationship of 
treatment group to outcome is assessed using the inverse probability of being observed as a 
weight in the GEE model. WEEs are advantageous because a) they are consistent with the ITT 
principle because participants with missing data are included in the analysis through the 
estimated weight, and b) unlike other methods for addressing missing data, they can be 
performed in conjunction with marginal structural modeling by multiplying both weights together.   
 
14.4 Sample Size Adequacy 
  
Power analyses were conducted for detectable mean changes from baseline (conservatively) 
assuming a within subject correlation of r=0.70. For between group differences, assuming 10% 
loss to follow up from all causes (mortality, attrition, etc.) by 16 weeks post randomization (CAP 
n=105 in the PUSH arm and this study will have n=30, so effective n=94 compared to n=27 
including attrition).  The study will have 80% power to detect differences of 0.475 standard 
deviations assuming two-sided tests and an alpha level of 0.05. These differences are 
considered small-to-moderate effects using Cohen’s criteria for interpretation of effect sizes 
(where 0.2 is “small” and 0.5 is “medium).  Given a 6MWT mean of 186.7 and SD=55.8 in the 
most recent overall sample from CAP (n=199, DSMB report May 2017), this would translate into 
a difference of 22.9.  Similar magnitude of effects (SD=0.41) are detectable comparing to other 
measures available in the CAP study (e.g, SPPB, 3MS, etc.). 
 
For outcomes only available in the CAP-MP study, the comparison sample is 19 subjects in 
CAP-MP PUSH.  Assuming 10% loss to follow up  (n=17 in CAP-MP PUSH group vs n=27 in 
pilot study), the study will have 80% power to detect between group differences of 0.62 standard 
deviations assuming two-sided tests and an alpha level of 0.05. This is considered a moderate-
to-large effect size by Cohen. 
 
Section 15: Data Capture, Data Management, and Quality Assurance 
 
15.1 Data Management 
 
15.1.1 Processing of Paper Data Forms 
Field staff will bring in data forms within 1 week of the visit and place them in the appropriate 
tray in the study office. Office staff will review each form for completeness and check any 
required fields. Submitted data forms will be tracked in an Access® database. Forms are then 
double entered into the appropriate data entry database and filed in the participant binder. 
 
15.1.2 Reportable Adverse Events Coding 
RAEs will be coded using MedDRA (version 15.1, release date September 1, 2012). The 
MedDRA coding dictionary is integrated with the study database. 
 

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48 
15.1.3 Extraction of Data for Analysis and Reporting 
Data will be extracted using StatTransfer and converted to SAS data sets for analysis and 
reporting.  Where required, data will be merged and recoded using validated SAS code to 
create “analysis data sets”.  Specifications for these analysis data sets will be drafted and 
updated as needed.  
 
15.2 Protection of Data 
 
15.2.1 Physical Security and Backup 
All tracking and data entry databases are password protected with limited access. Each are 
stored on the School of Medicine’s secure server. The server is backed up daily. SAS programs 
and datasets are also stored on the server and backed up daily. 
 
15.3 Study Management Database 
An Access® database will be used to track study visits, generate schedules of future study visits, 
status of participants, activities of study staff members, form completion, and form submission. 
The database will provide a standard way to track time-sensitive study activities throughout the 
study.  The study management database will be password-protected and saved on the server 
that will be automatically backed up daily. Access to the database will be restricted to office 
staff. There will be several standard reports available in the database to use for a variety of 
tracking issues.  Additional reports will be created as needed.  Data for the tracking database 
will come from tracking forms completed by study staff.   
 
15.4 Quality Assurance (QA) 
Quality assurance (QA) will be a shared responsibility of all study personnel. The goal of QA 
monitoring will be to track study progress and develop the information necessary to ensure: 1) 
enrollment of the required number of participants; 2) adherence to treatment protocol; 3) that 
data are reported completely, verifiably and in a timely fashion; and 4) participant safety, by 
accounting for expected AEs and RAEs. Study monitoring will be based on early implementation 
of reviews of accumulating data with rapid feedback to the PI regarding problem areas. The 
Investigative team will regularly review progress. 
 
15.4.1 Training 
Staff will be trained at the initial training session(s). Certification and recertification will be 
required in order to assure that staff have a clear understanding of the study protocol and 
Manual of Procedures (MOP). Separate training sessions will be provided for staff conducting 
study assessments, telephone interviewers, PTs providing the PUSH intervention, staff 
conducting screening and informed consent procedures, and the registered dieticians.  The 
study coordinator will attend all training sessions. 
 
Training sessions will cover recruitment; obtaining informed consent; collection of protocol-
specified data (both questionnaire and performance-based measures); scoring; completion of 
forms; capturing and reporting expected AEs and RAEs; administering the intervention; 
performing diet consults; and using the paper-based data forms.  
 
In preparation for training, staff will be asked to read background material (e.g., designated 
chapters in the MOP). The training session will involve both didactic and interactive 
components. Training for the different sessions will be provided by investigators with the 
appropriate expertise. For example, training the PTs to deliver the study interventions will be 
provided by the IM.  Whenever appropriate, trainees will be required to demonstrate acquired 

PUSH Plus Protein Pilot Protocol version3.0 
 
49 
skills. These demonstrations will be observed and critiqued by the trainers and other staff. 
Trainees will be certified to perform study procedures after successfully completing written and 
(when appropriate) performance tests.  
 
The study coordinator will be responsible for documenting that certification has been completed. 
 
15.4.2 Protocol Deviations 
Protocol deviations may jeopardize the study by breaching assurances made to the participants 
or by diminishing the validity of the study. Major deviations will be those that endanger 
participants, such as failure to protect safety during the intervention, or that undermine 
fundamental premises of the study, such as failure to provide the assigned intervention 
according to protocol or enrolling an ineligible participant. Minor deviations will be those that 
impede the progress of the study, such as not submitting data in a timely fashion.  
 
Major deviations will be reported annually to the UMB IRB and tracked using a protocol 
deviation log. The following classifications of protocol deviations will be captured, documented, 
and reviewed: 
 
1) Enrollment and consent deviations 
a. Enrollment of an ineligible participant 
b. Failure to obtain informed consent 
c. Enrollment of participant into another study 
 
2) IRB deviations 
a. Failure to keep IRB approval up to date 
b. Failure to submit study modification for approval 
 
3) Intervention deviations 
a. Required aspects of intervention not administered (e.g., dietician referral) 
 
Section 16: Participant Rights and Confidentiality  
 
16.1 Institutional Review Board (IRB) 
The study protocol will be reviewed by the UMB IRB. Subsequent modifications must be 
approved by UMB IRB before submission to the IRBS at respective study hospitals.  
 
16.2 Informed Consent Forms (ICF) 
It will be the sole responsibility of the PI to ensure that informed consent was properly obtained 
for every participant who entered into the study.  The ICF will describe the purpose of the study, 
the procedures to be followed, alternatives to participation, and the risks and benefits of 
participation.  It will also be explained that signing the consent form allows the study to confirm 
eligibility before starting the intervention.  Written informed consent will be obtained according to 
procedures reviewed and approved by the IRB.  Informed consent can be obtained anytime 
upon completion of phase 1 eligibility screening and prior to 26 weeks post hospital admission. 
Consent by a legally authorized representative will not be accepted.   
 
In some cases, a local hospital will allow the use of the UMB IRB approved consent form and/or 
the HIPAA Authorization Form.  However, local hospital IRBs may require that language be 
added to the consent form to correspond to local requirements. Staff will be responsible for 
ensuring that the correct version of the ICF is used. 

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50 
 
If there is a change in any of the study procedures or risks that may affect the participant, the 
ICF must be revised and undergo appropriate IRB review and approval.  Any participants 
enrolled in the study prior to such changes and who are still active in the study must sign the 
amended consent form. 
 
The study consent form will be provided to a potential participant for review prior to obtaining 
informed consent. The ICF may also be mailed to the participant and/or a family member so that 
s/he has sufficient time to read the document and, if desired, to have a family member or friend 
review the form before signing.  During the informed consent process, study staff will provide 
participants with adequate information concerning the study procedures, respond to individuals’ 
questions and concerns, and ensure that each individual understands all the information 
provided by assessing ability to provide informed consent.  A more detailed description of the 
informed consent process can be found in section 7.5.   
 
16.2.1 Disposition of Informed Consent Forms 
Because ICFs contain subject identifiers and protected health information (PHI), these forms will 
not be submitted with the data collection forms.  Originals of the ICF will be filed and maintained 
by the study coordinator in the participant binder which will be secured in a locked cabinet or 
office, separate from source documents that include no PHI.  A copy of the signed consent form 
will be given to the participant and this fact will be documented in the participant’s record.   
 
16.2.2 HIPAA Authorization 
The HIPAA Authorization for Research is an individual's signed permission to allow the study 
investigators to use or disclose the individual's PHI described in the authorization.  Once an 
individual has agreed to participate in the study and written informed consent has been 
obtained, the HIPAA Authorization for Research must also be explained and signed.  The 
HIPAA Authorization may be a stand-alone document or wording for the HIPAA Authorization 
may be incorporated into the text of the ICF.  The original signed authorization will be submitted 
to the study office and a signed copy will be given to the participant.   
 
16.3 Participant Confidentiality 
Potential participants will be provided with a clear understanding of how the information they 
provide will be used.  All investigators and staff involved in the study will be required to complete 
training on the protection of human subjects and HIPAA and to maintain proper certifications.    
 
To ensure confidentiality of study data, completed questionnaires and study forms will be kept in 
participant binders stored in locked offices, no unauthorized person will be permitted to see the 
binder or forms, names will be used only for the necessary purpose of making sure that the 
recorded information is for the person to whom it refers, and data will be summarized so that 
published results cannot be traced to individuals.  
 
On data collection forms, participants will be identified only by a unique study identification 
number. Staff will record names, contact information, and other direct identifiers to enable them 
to maintain contact with participants. Logs accessible only to the PI and key study personnel will 
link the study identification number to names. 
 
To protect study data from theft or unauthorized perusal or alteration, access to all computer 
files will be restricted to designated personnel through the use of passwords.  Access to the 
database and programs will be on a "need to use" basis (e.g., coordination staff cannot access 
main system programs).   

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51 
 
Computer security procedures, including multiple levels of password protection will be instituted. 
The study records will be identified by a unique participant identification number. Identification 
numbers will be recorded on each page of the paper forms.  Names and addresses of 
participants corresponding to each identification number will be kept in secure files at the clinical 
site. Final analysis data sets will not contain any directly or indirectly identifying information.   
Thus, dates of birth will be converted to age, other dates will be changed to counts of days from 
study entry, identification numbers will be replaced with sequence numbers, variables that could 
lead to deductive disclosure of the identity of individual participants will not be included nor will 
indirect identifiers such as infrequently occurring (e.g., fewer than 20 participants) outwardly 
manifest characteristics. 
 
Section 17: Research Publication Policy 
Publications will be operationally defined as manuscripts for publication; abstracts for platform 
or poster presentation at scientific and other professional meetings; slides for presentation at 
scientific and other professional meetings; doctoral dissertations; and master’s theses. 
 
The goal of our publication policy is to encourage and facilitate the publication of study results.  
The purposes of this policy are to ensure the following:  1) Publications will be of the highest 
scientific quality; 2) the study will be described in a consistent manner across publications; 3) 
measures are reported in consistent ways across publications; 4) proper acknowledgements are 
included; and 4) appropriate authorship credit is determined prior to submission of manuscripts 
for publication consideration. 
 
Publications will be overseen by the PUSH Plus Protein Pilot Study leadership (Drs. Magaziner, 
Orwig, and Gruber-Baldini).  These investigators will make recommendations to the 
Investigative team.  Final papers using data from CAP or CAP-MP may also need to be 
reviewed by the CAP Publication and Ancillary Studies Committee. 
 
A document describing the Publication Policy and Procedures appears in the Manual of 
Procedures. 
 
17.1 Concurrent Studies 
Study investigators agree not to conduct studies which would compete with or have a 
detrimental effect on the conduct of the PUSH Plus Protein Pilot study during the period of 
recruitment and follow-up. However, it is understood that each investigator has the right to 
conduct concurrent studies with participants who do not meet criteria for enrollment into PUSH 
Plus Protein.  Concurrent studies of patients who meet eligibility criteria for PUSH Plus Protein 
but are not enrolled in PUSH Plus Protein must be disclosed and reviewed by the Investigative 
team.   
 

PUSH Plus Protein Pilot Protocol version3.0 
 
52 
Section 18: Study Team Roster 
 
Name 
Role 
Address 
Phone number 
Fax number 
E-mail 
Study Chairs 
 
 
 
 
 
Jay Magaziner 
Study Chair 
University of MD Baltimore 
660 W. Redwood Street 
Suite 200 
Baltimore, MD 21201 
410-706-3553 
410-706-4433 
jmagazin@som.umaryland.edu  
 
 
Denise Orwig 
Study PI 
University of MD Baltimore 
660 W. Redwood Street 
Suite 200 
Baltimore, MD 21201 
410-706-8951 
410-706-4433 
dorwig@som.umaryland.edu 
 
 
NIA Project 
Officer 
 
 
 
 
 
Lyndon Joseph 
 
Project 
Officer 
National Institute on Aging 
7201 Wisconsin Ave. Suite 
525 A 
Bethesda, MD 20892   
301-496-6761 
301-480-1066 
josephlj@mail.nih.gov  
 
Biostatistics 
and Analysis 
 
 
 
 
 
Larry Magder 
Biostatistician 
University of MD Baltimore 
660 W. Redwood Street 
Suite 200 
Baltimore, MD 21201 
410-706-3253 
410-706-4433 
lmagder@som.umaryland.edu 
Ann Gruber-
Baldini 
Biostatistician 
University of MD Baltimore 
660 W. Redwood Street 
Suite 200 
Baltimore, MD 21201 
410-706-2444 
410-706-4433 
abaldin@som.umaryland.edu 
 
 
Intervention  
 
 
 
 
 
Doug Savin 
Intervention 
Monitor 
University of MD, Baltimore 
Department of Physical 
Therapy &  Rehab Science 
100 Penn St, Room 205 B 
Baltimore, MD 21201 
410-706-5210 
410-706-6387 
dsavin@som.umaryland.edu 
Kelly Ort 
Registered 
Dietician 
Baltimore VA Medical Center 
100 N. Greene Street 
Baltimore, MD 21201 
410-605-7000 
ext. 5434 
 
kelly.ort@va.gov 

PUSH Plus Protein Pilot Protocol version3.0 
 
53 
Name 
Role 
Address 
Phone number 
Fax number 
E-mail 
 
Clinical 
Direction 
 
 
 
 
 
Brock Beamer 
Study 
Physician 
Baltimore VA Medical Center 
100 N. Greene Street 
Room 4B-192 
Baltimore, MD 21201 
410-605-7000 
ext. 4870 
410-605-7971 
brock.beamer@va.gov 
Kenneth Koval 
 
 
 
Independent 
Safety 
Monitor 
Orlando Regional Medical 
Center 
86 W Underwood Street 
MP43 
Orlando FL 32732 
321-841-3479 
321-841-1870 
kenneth.koval@orlandohealth.com 
Ellen Binder 
Independent 
Safety 
Monitor 
Washington University 
School of Medicine 
Division of Geriatrics and 
Nutritional Science 
660 S. Euclid, Campus Box 
8303 
St. Louis, MO 63108 
314-286-2700 
314-286-2701 
ebinder@dom.wustl.edu 
 
Ram Miller 
Member 
Novartis Institutes for 
Biomedical Research 
220 Massachusetts Ave 
260A 
Cambridge, MA 02139 
617-871-4491 
 
ram.miller@novartis.com  
 
Publications 
and Ancillary 
Studies 
 
 
 
 
 
Ann Gruber-
Baldini 
Chair 
University of MD Baltimore 
660 W. Redwood Street 
Suite 200 
Baltimore, MD 21201 
410-706-2444 
410-706-4433 
abaldin@som.umaryland.edu 
 
 

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