Community-Based Rehabilitation Integrating Nurse-Led Mind-Body Exercise and Nutritional Supplementation for Frailty: A Three-Arm Randomized Controlled Trial
Phase: NA
Conditions: Frail Elderly
Sponsor: Universitas Airlangga

NIH-FDA Phase 2 and 3 IND/IDE Clinical Trial Protocol Template   
Community-Based Program Integrating Nurse-Led 
Mind-Body Exercise and Nutrition for Frailty 
 
Protocol Number: INA-1A72A0C 
National Clinical Trial (NCT) Identified Number:  - 
Principal Investigator: Rista Fauziningtyas, S.Kep.Ns., M.Kep., Ph.D. 
IDE Sponsor: Universitas Airlangga 
Funded by: Indonesia Endowment Fund for Education (LPDP) 
Version Number:  v.1.0 
12 February 2026 
 
 
Summary of Changes from Previous Version: 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
 
 
 
 
 
 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
1 

  
Table of Contents 
STATEMENT OF COMPLIANCE​
1 
1 PROTOCOL SUMMARY​
1 
1.1 Synopsis​
1 
1.2 Schema​
3 
1.3 Schedule of Activities (SoA)​
6 
2 INTRODUCTION​
6 
2.1 Study Rationale​
6 
2.2 Background​
7 
2.3 Risk/Benefit Assessment​
7 
2.3.1 Known Potential Risks​
7 
2.3.2 Known Potential Benefits​
8 
2.3.3 Assessment of Potential Risks and Benefits​
9 
3 OBJECTIVES AND ENDPOINTS​
9 
4 STUDY DESIGN​
10 
4.1 Overall Design​
10 
4.2 Scientific Rationale for Study Design​
11 
4.3 Justification for Dose​
11 
4.4 End of Study Definition​
11 
5 STUDY POPULATION​
11 
5.1 Inclusion Criteria​
11 
5.2 Exclusion Criteria​
12 
5.3 Lifestyle Considerations​
12 
5.4 Screen Failures​
12 
5.5 Strategies for Recruitment and Retention​
12 
6 STUDY INTERVENTION​
13 
6.1 Study Intervention(s) Administration​
13 
6.1.1 Study Intervention Description​
13 
6.1.2 Dosing and Administration​
13 
6.2 Preparation/Handling/Storage/Accountability​
14 
6.2.1 Acquisition and accountability​
14 
6.2.2 Formulation, Appearance, Packaging, and Labeling​
14 
6.2.3 Product Storage and Stability​
15 
6.2.4 Preparation​
15 
6.3 Measures to Minimize Bias: Randomization and Blinding​
16 
6.4 Study Intervention Compliance​
16 
6.5 Concomitant Therapy​
17 
6.5.1 Rescue Medicine​
17 
7 STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL​
18 
7.1 Discontinuation of Study Intervention​
18 
7.2 Participant Discontinuation/Withdrawal from the Study​
18 
7.3 Lost to Follow-Up​
19 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
2 

  
8 STUDY ASSESSMENTS AND PROCEDURES​
19 
8.1 Efficacy Assessments​
19 
8.2 Safety and Other Assessments​
21 
8.3 Adverse Events and Serious Adverse Events​
22 
8.3.1 Definition of Adverse Events (AE)​
22 
8.3.2 Definition of Serious Adverse Events (SAE)​
22 
8.3.3 Classification of an Adverse Event​
22 
1.1.2 Time Period and Frequency for Event Assessment and Follow-Up​
24 
1.1.3 Adverse Event Reporting​
24 
1.1.4 Serious Adverse Event Reporting​
25 
1.1.5 Reporting Events to Participants​
25 
1.1.6 Events of Special Interest​
25 
1.1.7 Reporting of Pregnancy​
25 
1.2 Unanticipated Problems​
26 
1.2.1 Definition of Unanticipated Problems (UP)​
26 
1.2.2 Unanticipated Problem Reporting​
26 
1.2.3 Reporting Unanticipated Problems to Participants​
27 
2 STATISTICAL CONSIDERATIONS​
27 
2.1 Statistical Hypotheses​
27 
2.2 Sample Size Determination​
28 
2.3 Populations for Analyses​
28 
2.4 Statistical Analyses​
28 
2.4.1 General Approach​
28 
2.4.2 Analysis of the Primary Efficacy Endpoint(s)​
29 
2.4.3 Analysis of the Secondary Endpoint(s)​
29 
2.4.4 Safety Analyses​
30 
2.4.5 Baseline Descriptive Statistics​
30 
2.4.6 Planned Interim Analyses​
30 
2.4.7 Sub-Group Analyses​
31 
2.4.8 Tabulation of Individual participant Data​
31 
2.4.9 Exploratory Analyses.​
31 
3 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS​
31 
3.1 Regulatory, Ethical, and Study Oversight Considerations​
31 
3.1.1 Informed Consent Process​
31 
3.1.2 Study Discontinuation and Closure​
32 
3.1.3 Confidentiality and Privacy​
33 
3.1.4 Future Use of Stored Specimens and Data​
33 
3.1.5 Key Roles and Study Governance​
34 
3.1.6 Safety Oversight​
34 
3.1.7 Clinical Monitoring​
35 
3.1.8 Quality Assurance and Quality Control​
35 
3.1.9 Data Handling and Record Keeping​
36 
3.1.10 Protocol Deviations​
37 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
3 

  
3.1.11 Publication and Data Sharing Policy​
37 
3.1.12 Conflict of Interest Policy​
38 
3.2 Additional Considerations​
38 
3.3 Abbreviations​
39 
3.4 Protocol Amendment History​
41 
4 REFERENCES​
43 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
4 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
STATEMENT OF COMPLIANCE 
 
(1)​ [The trial will be carried out in accordance with International Conference on Harmonisation 
Good Clinical Practice (ICH GCP) and the following:  
 
•​
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form.] 
1​
​
PROTOCOL SUMMARY 
1.1​
SYNOPSIS  
Title: 
Community-Based Program Integrating Nurse-Led Mind-Body Exercise and 
Nutrition for Frailty 
Study Description: 
This study is a community-based, three-arm randomized controlled trial 
evaluating the effectiveness of a nurse-led mind–body exercise program 
combined with nutritional supplementation, compared with mind–body 
exercise alone and usual care, in older adults with frailty. The intervention 
is delivered over the 8 weeks with outcomes assessed at predefined time 
points. The primary hypothesis is that participants receiving the combined 
mind–body exercise and nutritional supplementation intervention will 
demonstrate greater improvements in frailty status compared with those 
receiving exercise alone or education. 
Objectives: 
 
The primary objective of this study is to evaluate the effectiveness of a 
community-based, nurse-led mind–body exercise program combined with 
nutritional supplementation in improving frailty status among older adults, 
compared with mind–body exercise alone and education.  
The secondary objectives are to assess the effects of the interventions on 
physical function, mobility, body composition, pulmonary function, and 
inflammatory biomarkers, as well as to evaluate the feasibility and safety 
of implementing a nurse-led, community-based rehabilitation program for 
frail older adults. 
Endpoints: 
The primary endpoint of this study is the change in frailty status of older 
adults, measured using the Ina-FRAIL scale, from baseline to the end of the 
intervention period. Secondary endpoints include changes from baseline to 
post-intervention in lower extremity physical performance assessed by the 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
1 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
Short Physical Performance Battery (SPPB), functional mobility and fall risk 
assessed by the Timed Up and Go Test (TUGT), pulmonary function 
assessed by peak expiratory flow (PEF), body composition parameters 
including muscle mass, fat mass, and body mass index (BMI) assessed by 
bioelectrical impedance analysis (BIA), and inflammatory biomarkers 
related to frailty, specifically interleukin-6 (IL-6) and tumor necrosis 
factor-alpha (TNF-α). 
Study Population: 
Older adult age ≥65 years, a Frail Scale score of 1–3 (pre-frail) or 4–5 
(frail), ability to stand and walk independently without permanent assistive 
devices, live within the working area of ​a Community Health Center in 
Surabaya City. 
Phase: 
N/A 
Description of 
Sites/Facilities Enrolling 
Participants: 
The study will be conducted at a community-based sites, including primary 
health care centers, located in Surabaya, Indonesia (outside the United 
States). 
Description of Study 
Intervention: 
This study evaluates a nurse-led, community-based intervention consisting 
of mind-body exercise and nutritional supplementation over an 8-week 
period. The mind-body exercise program is conducted three times per week 
and includes low- to moderate-intensity movements tailored for frail older 
adults. Nutritional supplementation consists of a daily oral protein-based 
supplement in the form of Ensure Gold Strength Pro. Participants are 
assigned to one of three groups: mind-body exercise only, mind-body 
exercise combined with nutritional supplementation, or health education 
(arm control). 
Study Duration: 
10 months 
Participant Duration: 
2 months 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
2 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
1.2​
SCHEMA 
Example #1 Flow diagram (e.g., randomized controlled trial) 
 
 
Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening  
 
 
 
 
Visit 1 
Week 1  
 
 
Visit 2 
Week 2  
 
 
 
Visit 3 
Week 3 
 
 
Visit 4 
Week 4  
 
 
 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
3 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
Visit 5  
Week 5  
 
 
Visit 6  
Week 6  
 
 
Visit 7  
Week 7  
 
 
 
Visit 8  
Week 8  
 
 
 
 
 
 
 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
4 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
1.3​
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Scree
ning 
Day 0 
Enroll
ment/
Baseli
ne 
Visit 1, 
Day 1 
Study 
Visit 2  
Day 7  
+/-1 
day 
Study 
Visit 
3 
Day 
14 
+/- 1 
day 
Study 
Visit 4 
Day 
21 
+/-1 
day 
Study 
Visit 
5 
Day 
28 
+/-1 
day 
Study 
Visit 
6 
Day  
35 
+/-1 
day 
Study 
Visit 
7 
Day 
42 
+/-1 
day 
Study 
Visit 8 
Day 
49 
+/-1 
day 
Final 
Study 
Visit 
13​
Day 
84 
+/-1 
day  
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Eligibility assessment 
(inclusion/exclusion 
criteria) 
X 
 
 
 
 
 
 
 
 
 
Medical history & 
concomitant 
medication review 
X 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
Assesment 
(frailty, SPPB, TUGT, 
PEF, Body 
composition, Blood 
sample collection 
(IL-6, TNF-α)) 
X 
 
 
 
 
 
 
 
 
X 
Study intervention 
 
Participant education 
(control group) 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Mind–body exercise 
program 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Mind–body exercise 
program and 
Nutritional 
supplementation 
(Ensure Gold® 
Strength Pro) 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Follow-up & 
compliance 
monitoring 
(WA/Telp/home visit) 
 
 
 
X 
X 
X 
X 
X 
 
 
End-of-study 
evaluation 
 
 
 
 
 
 
 
 
 
X 
 
 
 
2​
​
INTRODUCTION 
 
2.1​
STUDY RATIONALE  
 
Frailty is a common geriatric syndrome among community-dwelling older adults, characterized by 
decreased physical reserve, reduced mobility, increased risk of falls, functional decline, hospitalization, 
and mortality. In Indonesia, the aging population is rapidly increasing, yet frailty is often underrecognized 
and undertreated in primary and community health care settings. Current standard care for older adults 
in the community mainly focuses on disease management and does not routinely include structured, 
nurse-led rehabilitation programs targeting frailty. 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
5 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
Although evidence from international studies suggests that mind–body exercise and nutritional 
supplementation can improve physical function and reduce frailty, there is limited evidence regarding 
the effectiveness of integrated, nurse-led interventions in community settings in Indonesia. Additionally, 
data on the impact of such interventions on inflammatory biomarkers related to frailty in Indonesian 
older adults remain scarce. 
 
Therefore, this clinical trial is conducted to evaluate whether a community-based rehabilitation program 
integrating nurse-led mind–body exercise with nutritional supplementation can improve frailty status 
and physical function outcomes among community-dwelling older adults, and to provide evidence to 
inform sustainable frailty management strategies in primary health care. 
 
2.2​
BACKGROUND  
Frailty is a common geriatric syndrome characterized by reduced physiological reserve, impaired physical 
function, and increased vulnerability to adverse health outcomes, including falls, disability, 
hospitalization, and mortality. In community-dwelling older adults, frailty is often underdiagnosed and 
inadequately managed, particularly in low- and middle-income countries such as Indonesia, where 
structured community-based rehabilitation programs are limited. 
Nonclinical and mechanistic evidence suggests that regular physical activity can improve muscle 
metabolism and modulate inflammatory processes associated with frailty, including elevated levels of 
interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Adequate protein intake has also been shown to 
support muscle mass maintenance and counteract sarcopenia-related functional decline in older adults. 
Clinical studies conducted in various countries have demonstrated that mind–body exercise 
interventions improve balance, mobility, muscle strength, and functional performance in older adults. 
Furthermore, multicomponent interventions combining physical exercise with nutritional 
supplementation have shown greater benefits in improving frailty status compared with single-modality 
interventions. Protein-based nutritional supplements have been widely used in older populations and 
are considered safe when administered orally at recommended doses. 
Despite this evidence, there is limited clinical trial data evaluating integrated, nurse-led, 
community-based interventions targeting frailty in Indonesia. Therefore, this randomized controlled trial 
aims to evaluate the effectiveness of a nurse-led mind–body exercise program, with and without 
nutritional supplementation, on frailty status, physical function, body composition, pulmonary function, 
and inflammatory biomarkers among community-dwelling older adults. The results are expected to 
provide evidence to support scalable frailty management strategies in primary and community 
healthcare settings. 
2.3​
RISK/BENEFIT ASSESSMENT   
 
2.3.1​
KNOWN POTENTIAL RISKS  
 
Based on available clinical evidence, product information, and published literature, the interventions 
used in this study are considered low risk. No investigational drugs or invasive medical devices are 
involved. 
1.​ Physical Risks 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
6 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
●​ Mind–body exercise: Potential immediate physical risks include mild muscle soreness, transient 
fatigue, dizziness, joint discomfort, or imbalance, particularly during the initial adaptation 
period. These risks are commonly reported in low- to moderate-intensity exercise programs for 
older adults and are generally self-limiting. 
●​ Nutritional supplementation: The protein-based nutritional supplement (Ensure Gold 
StrengthPro®) is a commercially available product with an established safety profile. Possible 
mild gastrointestinal symptoms such as bloating, nausea, or diarrhea may occur, especially in 
individuals with sensitivity to dairy-based products. 
●​ Blood sampling and physical assessments: Minor risks include temporary pain at the puncture 
site, bruising, minimal bleeding, or transient dizziness during blood collection. 
 
2.​ Psychological RisksParticipants may experience mild anxiety or discomfort related to physical 
performance testing, health assessments, or receiving information about their health status. These 
effects are expected to be temporary. 
3.​ Social, Legal, and Economic RisksNo significant social or legal risks are anticipated. From an 
economic perspective, participants may incur minimal indirect costs, such as time and 
transportation expenses related to attending intervention sessions. These potential economic 
burdens are mitigated by providing consumption or refreshments at each visit, and participation 
does not involve any direct financial cost or loss of income. 
4.​ Immediate RisksImmediate risks include mild musculoskeletal discomfort from exercise, transient 
gastrointestinal symptoms from supplementation, and minor discomfort related to blood sampling 
and physical assessments. 
5.​ Long-Range Risks 
No long-term or cumulative risks are anticipated based on current evidence. The interventions involve 
short-term, low-intensity activities and standard nutritional supplementation with no known long-term 
adverse effects when used as directed. 
 
Risk Mitigation and Alternative Procedures 
All exercise sessions are supervised by trained nurses, begin with warm-up and end with cool-down 
periods, and are individually adjusted based on participants’ daily physical condition. Participants are 
monitored before, during, and after sessions, and activities are modified or discontinued if discomfort 
occurs. 
Alternative procedures, such as higher-intensity exercise or pharmacological interventions, were 
considered but not included due to their higher risk profiles and lower feasibility in community-dwelling 
frail older adults. The selected interventions were chosen because they are non-invasive, 
evidence-based, and appropriate for safe implementation in community settings. 
 
 
2.3.2​
KNOWN POTENTIAL BENEFITS  
 
Based on existing clinical evidence and published literature, the interventions used in this study are 
expected to provide potential health benefits to participants and to contribute to broader public health 
knowledge. The mind–body exercise program and protein-based nutritional supplementation are 
non-invasive interventions with established use in older adult populations. 
 
Physical and Psychological Benefits 
Clinical studies have demonstrated that regular mind–body exercise can improve muscle strength, 
balance, mobility, flexibility, and overall physical performance in older adults. Such exercises are also 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
7 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
associated with improvements in breathing control, relaxation, sleep quality, and psychological 
well-being, including reduced stress and improved mood. Protein-based nutritional supplementation has 
been shown to support muscle mass maintenance, improve nutritional status, and enhance physical 
function in older adults, particularly those at risk of frailty. 
 
Immediate Potential Benefits 
Participants may experience short-term improvements in physical function, balance, mobility, breathing 
capacity, and perceived well-being during or shortly after the intervention period. Increased awareness 
of personal health status and engagement in regular physical activity may also occur as a result of 
participation. 
 
Long-Range Potential Benefits 
Long-term benefits may include sustained improvements in functional independence, reduced 
progression of frailty, lower risk of falls and disability, and improved quality of life. At the societal level, 
this study is expected to generate evidence supporting nurse-led, community-based frailty interventions 
that can be integrated into primary healthcare services. The findings may contribute to the development 
of scalable, cost-effective strategies for healthy aging and inform health policy and clinical practice in 
aging populations. 
 
2.3.3​
ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
The trial uses low-risk, non-invasive therapies to improve frailty in older persons living in the community. 
Evidence of successful, scalable, nurse-led frailty interventions—which are currently few in community 
settings—must be produced through exposure to low risks. Exercise-related soreness, nutritional 
supplements, and routine evaluations are among the mild and temporary dangers. Health screening, 
customized intervention modification, continued monitoring, and supervision by qualified nurses all help 
to reduce these hazards. 
 
Improvements in participants' frailty status, physical function, and general well-being are among the 
expected advantages, along with useful data to guide community-based frailty management. In general, 
the little dangers connected with involvement are outweighed by the possible advantages for both 
people and society. 
 
3​
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
The effectiveness of a nurse-led, 
community-based mind-body 
exercise program with and without 
nutritional supplementation in 
improving frailty status among 
older adults. 
 
 
Change in frailty status of older 
adults, measured by the 
Ina-FRAIL scale, from baseline to 
the end of the intervention 
period. 
 
The primary endpoint was 
chosen because frailty 
status is the main target of 
the intervention and 
represents a clinically 
meaningful outcome in 
older adults. The Ina-FRAIL 
scale is a validated and 
reliable instrument that 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
8 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
captures multidimensional 
aspects of frailty and is 
sensitive to changes 
following exercise and 
nutritional interventions, 
making it appropriate for 
evaluating the effectiveness 
of the study interventions. 
 
Secondary 
 
 
The effects of the nurse-led 
mind-body exercise and nutritional 
supplementation on physical 
function, mobility, body 
composition, pulmonary function, 
and inflammatory biomarkers 
related to frailty in older adults. 
 
 
Secondary endpoints include 
changes from baseline to 
post-intervention in lower 
extremity physical performance 
assessed by the Short Physical 
Performance Battery (SPPB), 
functional mobility and fall risk  
assessed by the Timed Up and Go 
Test (TUGT), pulmonary function 
assessed by peak expiratory flow 
(PEF), body composition including 
muscle mass, fat mass, and BMI 
assessed by bioelectrical 
impedance analysis (BIA), and 
inflammatory biomarkers related 
to frailty that is IL-6 and TNF-α.  
The secondary endpoints 
were chosen to provide 
supportive and 
complementary 
information on the effects 
of the intervention across 
multiple domains related to 
frailty, including physical 
performance, mobility, 
pulmonary function, body 
composition, and 
inflammatory biomarkers, 
providing a more thorough 
comprehension of the 
intervention's wider effects 
beyond the main result. 
 
Tertiary/Exploratory  
 
 
N/A 
N/A 
 
N/A 
 
 
4​
STUDY DESIGN  
 
4.1​
OVERALL DESIGN 
 
●​ H1 : Participants who received the combination intervention (mind-body exercises + nutritional 
supplements) showed a more significant reduction in frailty scores compared to the group that 
only received health education and mind-body exercises. 
●​ This study will use a randomized controlled trial (RCT) with three parallel groups and an assessor 
blinding method  
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
9 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
●​ To minimize bias, researchers use assessor blinding. Assessor blinding is a procedure in which the 
person measuring the research results is unaware of which group the participants are in. The 
goal is to ensure objective assessments based purely on clinical data. 
●​ The study will comprise three groups : a control group receiving health education, a second 
group receiving Nurse-Led Mind- Body Exercise (MBE), and a third group receiving MBE + 
Nutritional Supplementation. The intervention will be implemented over an eight-week period. 
Health education will be provided once a week, MBE will be administered 3 times a week, and 
nutritional supplements will be given daily. 
●​ The location of this research is only in one area, namely the Kalijudan Community Health Center 
area. 
 
4.2​
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
The selection of the control group with health education was chosen to provide basic standard of care 
without providing active physical or nutritional interventions, so that the difference in results was purely 
due to MBE exercise and supplements. This research is included in the superiority design because it 
compares 3 groups to find out which is the best. A potential problem that may arise from the control 
group is that participants may feel bored or disappointed that they are not getting physical exercise or 
supplements, so they may drop out of the study. 
 
4.3​
JUSTIFICATION FOR DOSE 
 
Participants will be provided with milk supplementation for a duration of 8 weeks. The dosage and 
serving size for each administration will be 230 mL. To prepare, 5 measuring spoons (45 grams) of 
powdered milk will be added to 198 mL of warm or cold water and stirred until dissolved. The 
reconstituted milk shall be consumed immediately or stored in a refrigerator and consumed within 24 
hours. How to store cans: first, store unopened cans at room temperature, opened cans should be tightly 
closed and stored in a cool, dry place, and opened cans should be consumed within three weeks. 
Supplementation is consumed twice a day, around 8 a.m. and 7 p.m., one hour after meals. 
 
4.4​
END OF STUDY DEFINITION 
 
A participant is considered to have completed the study if he/she has completed all phases of the study in 
the form of the final visit and the final physical examination procedures listed in the schedule of activities 
(SoA). 
 
5​
STUDY POPULATION 
 
5.1​
INCLUSION CRITERIA 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria :  
1.​ Provision of signed and dated informed consent form 
2.​ Age ≥ 65 years. 
3.​ FRAIL scale score of 0 (robust), 1–3 (pre-frail), and 4–5 (frail). 
4.​ Able to stand and walk independently without permanent assistive devices. 
5.​ Willingness to participate in an 8-week program (three sessions per week). 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
10 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
6.​ Hasil pemeriksaan ginjal baik (kreatinin lansia pria sekitar 0,9-1,3 mg/dL dan wanita 0,7-1,1 
mg/dL BUN) 
 
5.2​
EXCLUSION CRITERIA 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1.​ Severe heart or respiratory conditions that contraindicate exercise. 
2.​ Moderate to severe cognitive impairment (MoCA-InaMSE <18). 
3.​ Recent stroke or severe musculoskeletal disorder. 
4.​ Known allergy or intolerance to protein supplements. 
5.3​
LIFESTYLE CONSIDERATIONS 
 
Alcohol consumption is prohibited during the intervention. Tobacco consumption is not restricted, but 
will be recorded, and medications will continue to be taken as prescribed. 
 
5.4​
SCREEN FAILURES 
 
Participants who fail the Trial are considered participants who were successfully enrolled in the clinical 
trial but were not subsequently randomly assigned to the study intervention or enrolled in the study. 
Minimal information about participants who fail the Trial is required to ensure transparent reporting of 
participants who fail the Trial, to meet Consolidated Standards of Reporting Trials (CONSORT) publication 
requirements, and to respond to inquiries from regulatory authorities. Minimal information includes 
demographics, details of the Trial failure, eligibility criteria, and serious adverse events (SAEs). Individuals 
who do not meet the criteria for enrollment in this trial will not be retested. 
 
5.5​
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
●​ The target respondents are 48 elderly people aged ≥65. Participants come from residents within 
the Kalijudan Community Health Center (Puskesmas) working area in Surabaya. The source of 
participants is elderly people aged 65+ in the Kalijudan Community Health Center working area. 
Researchers will collaborate with community health center nurses to identify participants who 
meet the research criteria. Community health center nurses will direct community health post 
(Posyandu) community health worker (kader) to assist researchers in finding elderly people who 
meet the research criteria. Recruitment of participants will be assisted by community health 
center nurses and cadres. If agreed, the research coordinator will visit the elderly to explain the 
research details. Interventions are conducted in groups and individually. Group interventions are 
conducted during meetings and individual interventions are conducted independently by 
participants at home. The intervention will be conducted three times per week for 8 weeks, each 
session lasting 45 minutes. So there is a risk that respondents will forget or get bored. The 
researcher's strategy to ensure participants do not withdraw is by implementing an observation 
schedule, In weeks 4-5, direct observation and group exercises will be conducted once a week, 
and the researchers will check in with participants by phone on the other two days. Then, in 
week 5, check-ins will be conducted solely by phone via WhatsApp. in week 1-2, we will conduct 
joint exercises and direct monitoring by researchers; In weeks 3-4, group exercises will be 
conducted once a week, and the researchers will check in with participants by phone on the 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
11 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
other two days. Then, in week 5, check-ins will be conducted solely by phone via WhatsApp. In 
weeks 6-7, we will call participants with photo or video evidence by WhatsApp; and week 8, we 
will conduct joint exercises. Each meeting participant will be given a snack package. 
6​
STUDY INTERVENTION 
 
6.1​
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1​
STUDY INTERVENTION DESCRIPTION 
 
This study includes three parallel arms: (1) nurse-led mind–body exercise, (2) nurse-led mind–body 
exercise combined with nutritional supplementation, and (3) a control group receiving usual community 
care. 
1.​ The mind–body exercise intervention consists of structured, low-impact movements integrated 
with breathing control and relaxation techniques, delivered by trained nurses in community 
settings. The program is designed to improve balance, strength, flexibility, and mind–body 
awareness. Sessions are conducted regularly over the intervention period, with standardized 
duration and frequency across participants. 
2.​ The nutritional supplementation intervention involves oral nutritional supplements containing 
protein and essential micronutrients relevant to muscle health and frailty management. The 
supplement is commercially available and used in accordance with approved labeling, with no 
modification to formulation, dose, or route of administration. Supplements are administered 
orally at a standardized dose and frequency throughout the intervention period. 
3.​ The control group receives usual care provided in the community, without structured exercise or 
nutritional supplementation as part of the study protocol. 
No investigational drugs or medical devices under an Investigational Device Exemption (IDE) are used in 
this study. All interventions are non-invasive, commercially available, and pose minimal risk to 
participants. 
6.1.2​
DOSING AND ADMINISTRATION 
 
This study does not involve dose escalation or investigational drug dosing. Participants are assigned to 
one of three study arms with standardized intervention schedules. 
 
For the mind–body exercise intervention, all participants receive the same predefined program delivered 
by trained nurses. The “dose” is defined by session frequency and duration rather than pharmacological 
quantity. Exercise sessions are conducted at scheduled times in community settings, with a frequency of 
three sessions per week and a total duration of 50 minutes per session throughout the intervention 
period. Each session consists of a 5-minute warm-up, followed by 35 minutes of resistance and balance 
training, and concludes with a 10-minute cool-down using chair yoga. Participants are instructed to wear 
comfortable clothing, perform movements within their personal physical limits, and stop the session 
immediately if any discomfort or adverse symptoms occur. 
 
For the nutritional supplementation intervention, participants receive a protein-based nutritional 
supplement (Ensure Gold StrengthPro®)  in the form of a milk-based oral nutritional supplement for 8 
week. Each serving consists of 230 mL of prepared milk, made by adding 5 level scoops (45 grams) of 
milk powder into a glass, followed by 198 mL of warm or cold water. Participants are instructed to 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
12 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
consume the supplement twice daily, at approximately 08:00 and 19:00, and one hour after meals to 
improve tolerance. Intake is recommended at a consistent time each day, preferably after meals to 
reduce gastrointestinal discomfort. No dose escalation or reduction is planned. Missed doses are not 
replaced; participants resume the regular schedule the following day. 
 
The control group receives health education of elderly without structured exercise or nutritional 
supplementation as part of the study. 
 
No dose modifications, escalation, or de-escalation criteria are applicable, as the interventions are 
non-invasive, low risk, and standardized across participants. Safety monitoring is conducted throughout 
the study, and interventions may be temporarily paused if participants experience discomfort or adverse 
events, based on clinical judgment. 
 
6.2​
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
No text is to be entered in this section; rather it should be included under the relevant subheadings 
below.   
 
6.2.1​
ACQUISITION AND ACCOUNTABILITY 
 
The study interventions will be coordinated and overseen by the Principal Investigator (PI) in 
collaboration with Co-Investigators, including licensed professional nurses and a rehabilitation medicine 
physician, as well as research assistants. Implementation of the intervention arms will be led by Principal 
Investigator and Co-Investigator who is a professional nurse, with clinical supervision and guidance 
provided by a rehabilitation medicine physician to ensure participant safety and adherence to the 
intervention protocol. 
 
The nutritional supplementation product (protein milk) will be obtained centrally from the manufacturer 
and managed by the research team. The supplements will be stored, handled, and distributed to 
participants by trained study personnel according to the prescribed dosing schedule and manufacturer 
storage recommendations. The mind–body exercise intervention does not involve investigational drugs 
or devices and will be delivered directly to participants during scheduled sessions in community settings 
by trained nurses following a standardized protocol. 
 
Participants assigned to the control group will receive health education related to frailty and healthy 
aging in older adults. This educational intervention will be delivered by the Principal Investigator and a 
Co-Investigator, with research assistants, using standardized educational materials to ensure consistency 
across sessions. 
 
To minimize assessment bias, data collection for baseline (pre-intervention) and post-intervention 
measurements will be conducted by independent assessors who are not involved in delivering the 
intervention and who have expertise relevant to each outcome measure (e.g., physical performance, 
body composition, and laboratory assessments). No investigational pharmacy or drug repository is 
involved in this study. 
 
6.2.2​
FORMULATION, APPEARANCE, PACKAGING, AND LABELING  
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
13 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
The nutritional supplement used in this study is Ensure Gold StrengthPro Vanilla 800g (Abbott 
Laboratories), a commercially available, high-protein powdered milk formulation designed to support 
muscle strength, immunity, and overall nutritional status in adults. It contains a triple protein blend 
(whey, casein, and soy), calcium β-hydroxy-β-methylbutyrate (CaHMB), yeast beta-glucan (YBG), 28 
essential vitamins and minerals, and omega-3 and omega-6 fatty acids, which together help maintain 
muscle mass, immune function, and metabolic health. 
 
The product is packaged in sealed metal cans labeled by the manufacturer with product name, flavor, 
nutritional composition, batch number, and expiration date. Participants receive the 800g 
vanilla-flavored version, which is mixed with water to prepare a 230 mL serving (as described in the 
intervention protocol). No modifications to the product’s formulation, appearance, packaging, or labeling 
are made specifically for this study. 
 
The mind–body exercise intervention is non-pharmacological and has no physical formulation, 
packaging, or labeling. The intervention is supported by a standardized exercise protocol (SOP) and 
demonstration videos to ensure uniform delivery across sites. These materials are labeled for research 
use and include structured instructions for warm-up, core exercise movements, and cool-down using 
chair yoga. 
 
Participants in the control group receive health education on frailty and healthy aging using standardized 
printed and digital materials, including PowerPoint slides and leaflets developed by the research team. 
These materials are labeled internally for educational purposes and are not commercial therapeutic 
products. 
 
6.2.3​
PRODUCT STORAGE AND STABILITY 
 
Ensure Gold® StrengthPro is a commercially available powdered nutritional supplement supplied in 
sealed metal cans by the manufacturer. Unopened cans are stored at room temperature in a dry place, 
protected from direct sunlight, excessive heat, and humidity, in accordance with the manufacturer’s 
instructions. Once opened, the can must be tightly closed after each use and stored in a cool, dry place; 
the product should be used within three weeks after opening to maintain stability and nutritional quality.  
The reconstituted product should be consumed immediately after preparation. If not consumed 
immediately, it may be stored in a refrigerator and must be consumed within 24 hours. Expired products 
or unused supplements at the end of the study will be collected and disposed of according to 
institutional procedures. 
 
The mind–body exercise intervention does not involve a physical product requiring storage. Standardized 
exercise materials, including standard operating procedures (SOPs) and exercise demonstration videos, 
are stored in secure digital formats accessible only to authorized study personnel to ensure consistency 
and data integrity. 
 
Educational materials for the control group (PowerPoint slides and printed leaflets) does not involve a 
physical product requiring storage. Printed materials are protected from  damage, and digital files are 
stored on password-protected devices. No special stability requirements apply. 
 
6.2.4​
PREPARATION 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
14 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
The nutritional supplementation is prepared by study staff or participants according to standardized 
instructions. For each serving, 5 level measuring scoops (45 g) of Ensure Gold® StrengthPro powder are 
placed into a clean glass or container, followed by the addition of 198 mL of warm or cold drinking water 
to obtain a final volume of 230 mL. The mixture is stirred until fully dissolved. The prepared supplement 
is intended for immediate consumption. If not consumed immediately, it may be stored in a refrigerator 
and must be consumed within 24 hours, after which any remaining product is discarded. Participants are 
instructed to consume the supplement twice daily, approximately at 08:00 and 19:00, one hour after 
meals. Preparation procedures are explained verbally and in written form, and standardized instructions 
are included in the study SOP. 
 
No physical product preparation is required. Exercise sessions are delivered using a standardized 
nurse-led mind–body exercise program, supported by written SOPs and exercise demonstration videos. 
Sessions are conducted in community settings under the supervision of trained nurses, with guidance 
from a rehabilitation physician. Participants are instructed to wear comfortable clothing, follow the 
guided movements, and stop the session if discomfort occurs. 
 
The control intervention requires no product preparation. Educational sessions are delivered by the 
principal investigator and accompanying staff using PowerPoint presentations and printed leaflets. Study 
staff prepare the educational materials in advance according to standardized content to ensure 
consistency across sessions. 
 
6.3​
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
Participants will be randomly assigned in a 1:1:1 ratio to one of three study groups: (1) nurse-led 
mind–body exercise combined with nutritional supplementation, (2) nurse-led mind–body exercise 
alone, or (3) control group receiving health education. Randomization will be performed using a 
computer-generated random sequence prepared by an independent researcher not involved in 
participant recruitment, intervention delivery, or outcome assessment. Allocation concealment will be 
maintained using sequentially numbered codes. Due to the nature of the behavioral and nutritional 
interventions, blinding of participants and intervention providers is not feasible. To minimize bias, 
outcome assessors and data analysts will be blinded to group allocation, and data collection for pre- and 
post-intervention outcomes will be conducted by personnel not involved in intervention delivery. No 
interim unblinding is planned, and randomization codes will only be accessed if required for participant 
safety in the event of a serious adverse event, as determined by the principal investigator. Any 
intentional or inadvertent unblinding will be documented and reported according to the study protocol. 
The open-label design is considered appropriate, as primary and secondary outcomes are assessed using 
standardized and objective measurement tools to reduce observer bias. 
 
6.4​
STUDY INTERVENTION COMPLIANCE  
 
Adherence to the study protocol will be assessed throughout the intervention period for all study arms. 
For the mind–body exercise intervention, adherence will be monitored using structured attendance logs 
and follow-up records. During weeks 1 and 2, adherence assessment will be conducted directly during 
group exercise sessions held at the community center, where research assistants document attendance, 
session completion, and participant engagement. During weeks 3 and 4, adherence monitoring will be 
conducted in a blinded manner, consisting of one home visit per week by trained assessors who are not 
involved in intervention delivery, while additional follow-up will be performed by the research team via 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
15 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
WhatsApp or telephone communication. In week 5, adherence will be monitored exclusively through 
follow-up by the researchers via WhatsApp or telephone. During weeks 6 and 7, adherence reporting will 
be conducted through participant-initiated communication to the research team via WhatsApp or 
telephone. In week 8, adherence assessment will again be conducted directly during group exercise 
sessions at the community center. 
 
Adherence to the mind–body exercise intervention will be assessed based on participants’ ability to 
perform exercises including warm-up activities, balance and strength exercises, and cooling-down 
exercises. Attendance records, follow-up logs, and communication records will be used to calculate 
adherence rates based on the predefined frequency and duration of the exercise program. These records 
will document session participation, types of movements performed, any modifications due to physical 
limitations, and communication between participants and researchers during follow-up. 
 
For the nutritional supplementation intervention, participants will be provided with a supplement intake 
log to record daily consumption, timing, and any missed doses. Research assistants will review these logs 
weekly and verify adherence through brief interviews and inspection of returned empty or unused 
product containers, when applicable. In the control group, adherence to the educational intervention 
will be assessed through attendance records for education sessions and confirmation of receipt of 
educational materials. 
 
Documents for adherence assessment include attendance sheets, participant self-report logs, follow-up 
and communication logs, and researcher verification forms. These documents will serve as mandatory 
study records and will be used to calculate compliance rates for each intervention component.  
 
6.5​
CONCOMITANT THERAPY 
 
For this protocol, a prescription medication is defined as a medication that can only be prescribed by a 
properly authorized/licensed clinician. Data on permitted concomitant therapies will include all 
prescription medications, over-the-counter (OTC) medications, nutritional supplements (other than the 
study-provided supplement), and complementary or alternative therapies used by participants during 
the study period. This information will be collected at baseline/screening and updated at each study visit 
or follow-up assessment. Concomitant therapies are permitted provided they are stable and do not 
directly interfere with the study interventions or outcomes. Changes in medication, supplements, or 
therapies during the study will be documented, including type, dose, frequency, indication, and duration. 
Allowed concomitant therapies may potentially influence study outcomes (e.g., physical performance, 
frailty status, body composition, or inflammatory markers) through direct physiological effects or 
interactions with the nutritional supplementation. To address this, concomitant therapy data will be 
considered during data analysis, and where appropriate, sensitivity or subgroup analyses will be 
conducted to help distinguish the independent effects of the study interventions from those of 
concomitant treatments. 
 
6.5.1​
RESCUE MEDICINE 
   
The study will not routinely supply specific rescue medications as part of the protocol. Rescue therapy, if 
needed, will be obtained locally according to standard clinical practice and under the responsibility of 
licensed healthcare providers. Rescue treatments may include topical or oral medications for 
musculoskeletal discomfort, or other standard supportive treatments deemed necessary to ensure 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
16 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
participant safety and comfort. The use of rescue therapy is permitted at any time during the study if 
participants experience discomfort, pain, or other symptoms that cannot be managed conservatively. 
However, participants will be advised, where clinically appropriate, to delay the use of rescue 
medications for at least 24 hours after the study intervention session (mind–body exercise and/or 
nutritional supplementation) to minimize potential interference with outcome assessments. All use of 
rescue medications or procedures must be fully documented, including the date and time of 
administration, name of medication or treatment, dosage, route, duration, and clinical indication, and 
recorded in the Case Report Form (CRF). 
7​
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL 
No text is to be entered in this section; rather it should be included under the relevant subheadings 
below. 
 
Participants may withdraw voluntarily from the study or the PI may discontinue a participant from the 
study.  This section should state which adverse events would result in discontinuation of study 
intervention or participant discontinuation/withdrawal. In addition, participants may discontinue the 
study intervention, but remain in the study for follow-up, especially for safety and efficacy study 
endpoints (if applicable). Consider requiring separate documentation for study intervention 
discontinuation and participant discontinuation/withdrawal from the study. In addition, a dedicated Case 
Report Form (CRF) page should capture the date and the specific underlying reason for discontinuation of 
study intervention or participant discontinuation/withdrawal.  
 
7.1​
DISCONTINUATION OF STUDY INTERVENTION 
 
Discontinuation from mind-body exercises and supplements does not mean discontinuation from the 
study, and remaining study procedures should be completed as indicated by the study protocol.  If a 
clinically significant finding is identified (including, but not limited to changes from baseline) . After 
enrollment, the investigator or qualified designee will determine if any change in participant 
management is needed. Any new clinically relevant finding will be reported as an adverse event (AE). 
The data to be collected at the time of study intervention discontinuation will include the following: 
-​
Temporary discontinuation is performed for 2-7 days until symptoms improve and pain no longer 
interferes with daily activities. If the pain resolves or significantly reduces within 7 days, the 
intervention can be resumed. However, if pain persists after 7 days despite supportive therapy, 
the investigator will evaluate whether this is a systemic effect and consider permanent 
discontinuation. 
-​
Before permanently discontinuing the intervention, the researcher will conduct an “early 
termination visit” procedure which includes: recording the reason for discontinuation in detail 
on a case report form and a complete physical examination and vital signs. 
-​
Discontinuing the intervention does not result in participant withdrawal from the study. Data 
analysis will be conducted based on the Intent-to-Treat (ITT) principle. Data from participants 
who discontinue before the end of the study will remain included in the safety and efficacy 
analyses to the extent available. 
-​
Any adverse events observed at the time of discontinuation will be monitored until the condition 
is stable, resolved, or there is another adequate medical explanation. Researchers will continue 
to follow up by phone and monthly visits until the end of the study. 
 
7.2​
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
17 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons : 
1.​ Significant study intervention non-compliance. 
2.​ If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant. 
3.​ Disease progression which requires discontinuation of the study intervention 
4.​ If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
5.​ Participant unable to receive Mind-Body Exercise and Nutritional Supplementation for 7 days. 
The reason for participant discontinuation or withdrawal from the study will be recorded on the 
Discontinuation Case Report Form (CRF). Subjects who sign the informed consent form and are 
randomized but do not receive the study intervention may be replaced.  Subjects who sign the informed 
consent form, and are randomized and receive the study intervention, and subsequently withdraw, or 
are withdrawn or discontinued from the study, will not be replaced.  
7.3​
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he or she fails to return for <specify number of visits> 
scheduled visits and is unable to be contacted by the study site staff.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
1.​ A participant will be considered lost to follow-up if he or she fails to return for 3 scheduled visits 
and is unable to be contacted by the study site staff. 
2.​ The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
-​
The site will attempt to contact the participant and reschedule the missed visit and 
counsel the participant on the importance of maintaining the assigned visit schedule and 
ascertain if the participant wishes to and/or should continue in the study. 
-​
Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls 
and, if necessary, visiting the participant's house). These contact attempts should be 
documented in the participant’s medical record or study file.  
-​
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up 
 
8​
STUDY ASSESSMENTS AND PROCEDURES 
No text is to be entered in this section; rather it should be included under the relevant subheadings 
below. 
 
8.1​
EFFICACY ASSESSMENTS  
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
18 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
All study procedures and evaluations are designed to support the determination of efficacy in 
accordance with the protocol's primary and secondary objectives. The study includes sequential phases 
consisting of screening, enrollment/baseline assessment, intervention period, post-intervention 
follow-up assessment, and end-of-study evaluation. 
1.​ Screening and Eligibility Assessment 
Potential participants will be screened at week 0. Screening procedures include verifying 
inclusion and exclusion criteria, collecting demographic information, medical history, current 
medications and supplements, and assessing baseline frailty using a validated frailty instrument. 
Eligibility decisions will be made based on pre-specified inclusion and exclusion criteria. 
Participants who do not meet eligibility requirements will not proceed to the baseline 
assessment. 
2.​ Baseline Assessment (Pre-Intervention) 
Eligible participants who provide informed consent will undergo a baseline evaluation prior to 
randomization. This includes assessments of physical performance (e.g., Short Physical 
Performance Battery), functional mobility and fall risk (Timed Up and Go Test), pulmonary 
function (Peak Flow Meter), body composition (Bioelectrical Impedance Analysis), and collection 
of biological specimens for inflammatory and metabolic biomarkers (e.g., IL-6 and TNF-α). 
Baseline questionnaires and standardized instruments will be administered by trained and 
qualified personnel. 
3.​ Study Intervention and Control ProceduresParticipants will be randomized into one of three 
study groups: 
a.​ Mind-body exercise intervention 
Participants in the intervention group received a standardized mind-body exercise 
program led by trained nurses under the supervision of a rehabilitation physician. 
Exercise sessions took place three times a week, lasting approximately 45–50 minutes 
per session, in a community setting. Each session included: 
●​ Warm-up (≈5 minutes): light stretching and breathing exercises; 
●​ Core exercise (≈30 minutes): resistance and balance training movements; 
●​ Cool-down (≈10 minutes): relaxation and flexibility exercises incorporating chair 
yoga and breathing techniques. 
All participants followed a predetermined exercise protocol, with movements tailored to 
individual physical capacity. Participants were instructed to stop exercising if discomfort 
occurred. 
b.​ Mind-body exercise combined with nutritional supplementation 
Participants assigned to the combined intervention arm receive oral protein nutritional 
supplementation in the form of a commercially available milk-based supplement (Ensure 
Gold® StrengthPro). The supplement is provided twice daily for 8 weeks, with one 
serving prepared as 230 mL per serving according to manufacturer instructions. The 
supplement is consumed approximately one hour after meals to support protein intake 
and muscle maintenance during the rehabilitation program 
c.​ A control group receiving health education 
Participants in the control group receive standard health education for older adults with 
frailty, delivered by the principal investigator and study team. Education sessions cover 
topics related to healthy aging, frailty prevention, physical activity, and nutrition, using 
PowerPoint presentations and printed educational leaflets, without structured exercise 
or nutritional supplementation. 
4.​ Follow-up and Outcome Assessment (Post-Intervention) 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
19 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
Participants will be monitored throughout the intervention period and assessed at 
predetermined time points according to the Activity Schedule. Post-intervention follow-up 
procedures will include reassessment of frailty status, assessment of physical performance (e.g., 
Short Physical Performance Battery), functional mobility and fall risk (Timed Up and Go Test), 
pulmonary function (Peak Flow Meter), body composition (Bioelectrical Impedance Analysis), 
and collection of biological specimens for inflammatory and metabolic biomarkers (e.g., IL-6 and 
TNF-α), adherence monitoring, and documentation of concomitant therapies and rescue 
medications. 
8.2​
SAFETY AND OTHER ASSESSMENTS 
 
This study includes a series of procedures and evaluations conducted to ensure participant safety, 
determine eligibility, support the understanding of the study intervention, and collect study data. All 
procedures are performed by qualified personnel according to standardized operating procedures, with 
detailed instructions provided in the Standard Operational Procedures (SOP). 
1.​ Screening and Enrollment Procedures 
Potential participants undergo screening procedures. Screening includes review of demographic 
data, medical history, frailty status assessment, and confirmation of inclusion and exclusion 
criteria. Eligibility decisions are made based on predefined criteria, and only meeting 
participants all requirements are enrolled. Written informed consent is obtained prior to any 
study-specific procedures. No separate screening protocol is used; screening is integrated into 
this study protocol. 
2.​ Baseline and Follow-up Safety Assessments 
A targeted physical examination is conducted at baseline, including measurement of height, 
weight, and functional mobility, as appropriate for older adults with frailty. Vital signs (blood 
pressure, heart rate, and respiratory rate) are assessed at baseline and during selected follow-up 
visits to monitor safety. 
3.​ Biological Specimen Collection and Laboratory Evaluations 
Blood samples were collected at baseline and post-intervention for assessment of inflammatory 
and metabolic biomarkers (e.g., IL-6 and TNF-α) related to frailty. All samples are processed using 
standardized laboratory methods to ensure consistency across measurements. Laboratory 
analyzes are conducted in qualified laboratories following applicable regulations; Detailed 
procedures for sample handling, storage, and analysis are described in the SOP. 
4.​ Intervention Monitoring and Counseling 
Participants receive counseling related to safe participation in mind–body exercise and 
appropriate consumption of nutritional supplementation. Instructions include physical activity 
precautions, recognition of discomfort, and dietary guidance related to supplement intake. 
5.​ Adherence and Outcome Assessments 
Adherence to study interventions is monitored through attendance records, follow-up logs, and 
communication records. Functional performance tests and questionnaires assessing frailty status 
and related outcomes are administered by trained assessors who are not involved in delivering 
the intervention, when feasible, to reduce bias. 
6.​ Adverse Event Monitoring 
All adverse events (AEs) and serious adverse events (SAEs) were actively monitored throughout 
the study period. Participants are instructed to report any discomfort or health changes 
immediately. Reported AEs/SAEs are documented, evaluated by the study team, and followed 
until resolution or stabilization. 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
20 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
Overall, these procedures are designed to ensure participant safety, data quality, and reliable assessment 
of study outcomes, while minimizing participant burden. 
   
8.3​
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.3.1​
DEFINITION OF ADVERSE EVENTS (AE) 
 
An adverse event (AE) is defined as any untoward medical occurrence associated with participation in 
this study, including during the administration of the mind–body exercise program or nutritional 
supplementation, whether or not it is considered related to the study intervention, in accordance with 
the FDA definition (21 CFR 312.32(a)). AEs may include physical, psychological, or functional complaints, 
abnormal findings, or symptoms that occur or worsen during the study period, regardless of causal 
relationship to the intervention. 
 
8.3.2​
DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
 
A serious adverse event (SAE) is defined as any adverse event (AE) or suspected adverse reaction that, in 
the judgment of the investigator or sponsor, results in one or more of the following outcomes, in 
accordance with FDA regulations (21 CFR 312.32[a]): 
1.​ Death 
2.​ A life-threatening adverse event 
3.​ Inpatient hospitalization or prolongation of existing hospitalization 
4.​ A persistent or significant disability/incapacity or substantial disruption of the ability to conduct 
normal life functions 
In addition, important medical events that may not result in death, be immediately life-threatening, or 
require hospitalization may also be considered serious if, based on appropriate medical judgment, they 
may jeopardize the participant and may require medical or surgical intervention to prevent one of the 
outcomes listed above. For this study, examples of potential SAEs may include, but are not limited to, 
serious falls resulting in fracture or hospitalization, severe cardiovascular events occurring during or after 
exercise sessions, severe allergic reactions to nutritional supplementation, or other unexpected serious 
medical conditions temporally associated with study participation. 
 
8.3.3​
CLASSIFICATION OF AN ADVERSE EVENT 
1.1.1.1​
SEVERITY OF EVENT 
 
All adverse events (AEs) will be assessed and graded for severity by the study clinician in accordance with 
a protocol-defined grading system. The grading of AE severity will be based on clinical judgment, 
considering the intensity of symptoms, the degree of functional limitation, and the need for medical 
intervention. The grading approach is adapted from commonly used clinical toxicity and safety 
assessment frameworks and is appropriate for non-pharmacological interventions, including 
exercise-based and nutritional interventions. For adverse events not specifically included in a 
protocol-defined grading scale, the following severity categories will be applied: 
1.​ Mild – Events require minimal or no intervention and do not interfere with the participant’s 
usual daily activities. 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
21 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
2.​ Moderate – Events cause discomfort or functional limitation that interferes to some extent with 
daily activities and may require simple therapeutic measures. 
3.​ Severe – Events significantly interfere with normal daily activities, may require medical 
treatment or clinical intervention, and may be potentially life-threatening or result in 
hospitalization. 
It is noted that the term “severe” refers to the intensity of an adverse event and does not necessarily 
indicate that the event meets the criteria for a serious adverse event (SAE). The distinction between 
severity and seriousness will be clearly maintained in accordance with regulatory definitions. 
 
1.1.1.2​
RELATIONSHIP TO STUDY INTERVENTION 
 
All adverse events (AEs) will have their relationship to study intervention or study participation assessed 
by the study clinician based on temporal relationship, clinical judgment, and consideration of alternative 
etiologies. In accordance with good clinical practice, the study intervention will always be considered a 
possible cause of an AE unless an alternative explanation is clearly established. If there is any doubt as to 
whether a clinical observation constitutes an AE, the event will be reported. The assessment of 
relatedness will take into account the natural history of frailty, age-related comorbidities, intercurrent 
illness, concomitant medications or supplements, study-related procedures, physical activity–related 
events, accidents, and other external factors. The degree of certainty regarding the relationship between 
the AE and the study intervention will be categorized using the following scale: 
1.​ Related – There is a reasonable possibility that the AE is causally related to the study 
intervention, including a plausible temporal relationship between the intervention and the 
event, and no more likely alternative explanation. 
2.​ Possibly Related – The AE occurred within a reasonable time after the study intervention, but 
other contributing factors such as underlying disease, concurrent illness, or concomitant therapy 
may also have played a role. 
3.​ Unlikely to be Related – The temporal relationship between the AE and the study intervention 
makes a causal association improbable, and other etiologies provide a more plausible 
explanation. 
4.​ Not Related – The AE is clearly attributable to causes other than the study intervention, with a 
documented alternative etiology. 
 
1.1.1.3​
EXPECTEDNESS  
 
Expected adverse reactions are adverse events (AEs) that are known to occur with the study 
interventions and will be collected in a standardized and systematic manner using a severity grading 
scale based on functional impact and magnitude of reaction. The determination of expected AEs will be 
based on reference safety information obtained from approved product labeling for the nutritional 
supplementation (Ensure Gold®) and published literature and established exercise safety guidelines for 
mind–body exercise in older adults. Expectedness is assessed based on AEs that have been previously 
observed with these interventions, rather than on theoretical or anticipated effects. 
 
An adverse event or suspected adverse reaction will be considered unexpected if it is not listed in the 
approved product labeling, published safety information, or protocol-described risk profile, or if it occurs 
at a greater specificity, severity, or frequency than previously documented. Unexpected AEs also include 
events that are known to occur with a class of products or interventions but have not been reported 
with the specific intervention under investigation. The Principal Investigator (PI) will be responsible for 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
22 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
determining whether an AE is expected or unexpected based on available safety references and clinical 
judgment. An AE will be classified as unexpected if the nature, severity, or frequency of the event is not 
consistent with the previously described risk information for the study interventions. 
1.1.2​
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
Adverse events (AEs) and serious adverse events (SAEs) will be identified through multiple sources, 
including scheduled study visits, direct observation during intervention sessions, structured interviews, 
telephone or WhatsApp follow-up, and spontaneous reports from participants or caregivers. Study 
personnel will also identify AEs during review of participant records or when participants seek medical 
care during the study period. All AEs that do not meet the criteria for SAEs will be recorded in the Case 
Report Form (CRF). Information collected will include a description of the event, date and time of onset, 
severity grading, assessment of relationship to the study intervention, actions taken, and date of 
resolution or stabilization. All AEs occurring after informed consent is obtained will be documented 
regardless of their perceived relationship to the study intervention and will be followed until resolution, 
stabilization, or study completion.  
 
Baseline medical conditions present at screening will not be reported as AEs unless there is a clinically 
significant worsening during the study, in which case the change will be recorded as an AE. Changes in 
severity of an AE over time will be documented to allow assessment of duration at each severity level. 
Intermittent events will be recorded with separate onset and resolution dates for each episode. Solicited 
AEs will be actively assessed at each study contact using standardized safety monitoring questions 
related to common and expected effects of the interventions, including musculoskeletal discomfort, 
fatigue, dizziness, balance disturbances, and gastrointestinal symptoms related to nutritional 
supplementation. Unsolicited AEs will be captured through open-ended questioning such as, “Have you 
noticed any new symptoms or changes in your health since participating in the study?” To avoid double 
capture, events reported as solicited AEs will not be re-entered as unsolicited events. 
 
Non-serious AEs will be collected from the time of informed consent until 7 days after completion of the 
intervention, while SAEs will be collected from informed consent through the entire study period and up 
to 30 days after the last study intervention. All SAEs will be followed until resolution, stabilization, or 
determination of a chronic condition. AE and SAE assessments will be conducted by qualified study 
clinicians, including trained nurses and physicians, using protocol-defined assessment tools. Participants 
experiencing ongoing or unresolved AEs at study completion will be followed until the event is resolved 
or considered clinically stable. 
 
1.1.3​
ADVERSE EVENT REPORTING  
 
Investigators are responsible for the identification, documentation, assessment, and timely reporting of 
all adverse events (AEs) and serious adverse events (SAEs) occurring during the study period. All 
non-serious AEs will be recorded in the Case Report Form (CRF). All SAEs will be reported within 24 hours 
of the investigator’s awareness of the event. Follow-up information, including outcome and causality 
assessment, will be submitted as it becomes available until the event is resolved or considered clinically 
stable. Detailed procedures, including reporting pathways, notification timelines, roles and 
responsibilities of study personnel. 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
23 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
The PI is responsible for reviewing and signing off on all AE and SAE reports prior to submission. Study 
staff, including research nurses and research assistants, are responsible for initial documentation and 
timely notification to the PI. Certain disease-related events (DREs) that are common in the elderly 
population with frailty, such as transient fatigue, mild musculoskeletal discomfort, or minor balance 
instability not resulting in injury are anticipated and will not be reported as SAEs unless they meet 
seriousness criteria. These events will be recorded in the CRF and monitored descriptively throughout 
the study to assess overall safety trends. 
 
1.1.4​
SERIOUS ADVERSE EVENT REPORTING  
 
Clinical researchers will promptly report any serious adverse events to the sponsor and ethics committee 
as soon as possible, within 24 hours of receiving the information. Reporting is mandatory regardless of 
whether the event is related or unrelated to the mind-body workout intervention or the nutritional 
supplement administered. Researchers will assess whether there is a potential causal link between the 
intervention (e.g., a physical injury from exercise or an allergic reaction to the supplement) and the 
event. Each SAE will be closely monitored by the research team until the participant's condition is 
deemed stable. Sponsors are responsible for reporting any unexpected and life-threatening serious 
reactions to the regulatory authorities (BPOM or relevant health authorities) as soon as possible, within 
a maximum of 7 days. 
 
1.1.5​
REPORTING EVENTS TO PARTICIPANTS  
All participants will be given a detailed explanation of the potential risks during the informed consent 
process. If an adverse or serious adverse event occurs during the study, the following actions will be 
taken: 
1.​ Detection findings through clinical observation during training sessions or through laboratory 
screening that is part of the nutritional supplementation protocol. 
2.​ Immediate communication, researchers will contact participants (and families if necessary in 
cases of SAE) directly by telephone or face-to-face to explain the findings within 24 hours. 
3.​ The follow-up plan is for researchers to provide a letter of recommendation for participants to 
consult independently at a primary health care facility (community health center/clinic). If a 
life-threatening condition is identified, researchers will immediately refer participants to the 
emergency room of a partner hospital. 
4.​ The costs of initial diagnosis of incidental findings are fully covered by the researcher. Long-term 
treatment costs for incidental findings are covered by the participant's personal insurance (BPJS). 
5.​ Risk transparency, researchers will explain whether the incident is directly related to Mind-Body 
Exercise and the provision of nutritional supplements or is an independent medical condition. 
6.​ If new security findings of general significance emerge, all participants will be re-informed so 
they can consider continuing their participation. 
7.​ The results of the participants' personal health examinations will be reported to the participants 
while the overall results of the study will be shared with the participants through a summary 
report or scientific publication after the study is completed. 
 
1.1.6​
EVENTS OF SPECIAL INTEREST  
 
N/A 
1.1.7​
REPORTING OF PREGNANCY  
N/A 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
24 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
 
 
1.2​
UNANTICIPATED PROBLEMS 
 
1.2.1​
DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome 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 Institutional Review Board 
(IRB)-approved research protocol and informed consent document; and (b) the characteristics of 
the participant population being studied; 
•​
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
•​
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. 
 
In this study, unforeseen issues that may arise include: 
•​
The severity of allergies due to nutritional supplement consumption is beyond expectations. 
•​
Participants fall or break bones while performing Mind-Body Exercises. 
•​
Participants experience trauma or extreme anxiety after the exercise. 
•​
Participants have to incur significant medical expenses not covered by the study due to 
unforeseen events. 
•​
Personal data leaks (e.g., their medical history is leaked), causing participants to feel 
embarrassed or socially disadvantaged. 
 
 
1.2.2​
 UNANTICIPATED PROBLEM REPORTING  
 
The principal investigator will ensure that all unforeseen issues are reported to the ethics committee. Clinical 
research staff or research assistants are responsible for identifying incidents in the field, documenting them, and 
promptly reporting them to the principal investigator for signature before submission to the regulatory authority. 
-​
Contents of the report 
The report contains the protocol identity (research title, protocol number, principal investigator's name, 
and ethics approval number), detailed description (detailed explanation of the incident, experience, or 
outcome that occurred), basic analysis of the unanticipated problems (explanation of why the incident is 
considered a unanticipated Problems), and corrective actions (description of any protocol changes that 
have been made or proposed, changes to the informed consent form, or other corrective actions in 
response to the unanticipated problem). 
-​
Reporting Timeline 
Any unanticipated problem, including a serious adverse event, will be reported to the ethics committee 
within 24 hours of the researcher's discovery. Unanticipated problems that are not severe adverse events, 
such as privacy violations or product contamination without any participant illness, will be reported to the 
ethics committee within 5 days of the researcher's discovery.  
-​
Reporting Process 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
25 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
After an unanticipated problem is detected, research staff must verbally report it to the principal 
investigator within 12 hours. The principal investigator evaluates the unanticipated problem  criteria and 
signs the unexpected problem report form. The report is then submitted to the ethics committee. 
 
 
1.2.3​
REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
Individual level communication :  
-​
The principal investigator will contact participants directly by telephone or face-to-face within 24 
hours, after an unanticipated problem is identified. 
-​
Participants will be given an in-depth explanation of the issue, its potential impact on their 
health, and the medical steps that have been or will be taken. 
-​
Participants will be given updated information regarding the risks identified and asked again 
about their willingness to continue or stop the research (re-consenting). 
 
Aggregate level communication  
If an unanticipated problem occurs that has the potential to affect the risk profile of the entire 
participant group, then: 
-​
All participants currently on the course will be promptly informed of the new risks via group 
meetings  or electronic messages (WhatsApp). 
-​
All participants will be asked to review and sign an updated version of the Informed Consent 
form that includes these new risks. 
-​
Di akhir studi, ringkasan mengenai Masalah Tak Terduga yang signifikan dan bagaimana masalah 
tersebut dikelola akan disertakan dalam laporan hasil studi agregat yang dibagikan kepada 
peserta (tanpa membuka identitas individu yang mengalami kejadian tersebut). 
 
2​
STATISTICAL CONSIDERATIONS  
 
2.1​
STATISTICAL HYPOTHESES 
 
●​ Primary Efficacy Endpoint(s):  
Endpoint: 
Change in frailty status from baseline to the end of the 8-week intervention, measured using a 
validated frailty assessment tool. 
Type of comparison:​
Superiority (between-group comparison) 
Null Hypothesis (H0):​
There is no difference in the change in frailty status from baseline to 8 weeks among older adults 
receiving (1) nurse-led mind–body exercise combined with nutritional supplementation, (2) 
nurse-led mind–body exercise alone, and (3) control (health education). 
Alternative Hypothesis (H1):​
Older adults receiving nurse-led mind–body exercise combined with nutritional supplementation 
will demonstrate a significantly greater improvement in frailty status from baseline to 8 weeks 
compared with those receiving mind–body exercise alone or control (health education). 
●​ Secondary Efficacy Endpoint(s): 
Endpoints:​
Changes from baseline to 8 weeks in: 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
26 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
a.​ Lower extremity physical performance (Short Physical Performance Battery) 
b.​ Functional mobility and fall risk (Timed Up and Go Test) 
c.​ Pulmonary function (Peak Expiratory Flow) 
d.​ Body composition (muscle mass, fat mass, and BMI measured by BIA) 
e.​ Inflammatory biomarkers related to frailty (IL-6 and TNF-α) 
Type of comparison:​
Superiority (between-group comparison) 
Null Hypothesis (H0):​
There are no differences in secondary outcome measures from baseline to 8 weeks among the 
three study groups. 
Alternative Hypothesis (H1):​
Participants in the combined intervention group (mind–body exercise plus nutritional 
supplementation) will show significantly greater improvements in secondary outcome measures 
from baseline to 8 weeks compared with the exercise-only and control groups. 
 
2.2​
SAMPLE SIZE DETERMINATION 
 
The sample size was determined using Cochran’s formula, based on the primary outcome of change in 
frailty score from baseline to 8 weeks. Using a 95% confidence level (Z = 1.96), an assumed population 
proportion of 0.5, and an acceptable margin of error, the minimum required sample size was calculated 
to be 12 participants per group. To account for potential attrition, withdrawal, or incomplete data during 
the intervention period, the sample size was increased to 16 participants per group. This adjustment was 
made to ensure an adequate evaluable sample and maintain the robustness of the analysis. The final 
planned sample size is therefore 48 participants in total across the three study arms. This sample size is 
considered appropriate for this preliminary randomized controlled trial and will provide data to inform 
sample size estimation for future larger-scale studies. 
 
2.3​
POPULATIONS FOR ANALYSES 
 
The ITT dataset will include all participants who are randomized into one of the three study groups, 
regardless of their level of adherence to the assigned intervention, protocol deviations, or withdrawal 
after randomization. Participants will be analyzed according to their originally assigned groups. This 
dataset will serve as the primary analysis population for efficacy outcomes to preserve the benefits of 
randomization. 
 
2.4​
STATISTICAL ANALYSES 
 
2.4.1​
GENERAL APPROACH 
 
Descriptive Statistics 
-​
Continuous Data: Data such as frailty scores (Fried Phenotype), handgrip strength, and gait 
speed will be presented as Mean (Average) and Standard Deviation (SD) if normally distributed. 
If the data is not normally distributed, it will be presented as Median and Interquartile Range 
(IQR). 
-​
Data Categories: Demographic characteristics such as gender, education level, and medical 
history will be presented as frequency (n) and percentage (%). 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
27 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
Hypothesis Testing and Significance 
-​
All statistical tests will be conducted two-tailed. 
-​
The level of statistical significance is set at a p-value <0.05 with a 95% confidence interval.  
-​
To compare the intervention effects between the three groups (Mind-Body & Goldsure 
combination vs. Mind-Body alone vs. Control), an Analysis of Variance (ANOVA) or Mixed-model 
ANOVA will be used to examine the interaction between time and group (Pre-test, Post-test 1, 
Post-test). 
Statistical Assumption Check 
-​
Normality Test: Before conducting inferential testing, data distribution will be checked using the 
Shapiro-Wilk or Kolmogorov-Smirnov test. 
-​
Corrective Procedure: If the assumption of normality is not met, researchers will transform the 
data or use a relevant non-parametric test (such as the Kruskal-Wallis test instead of ANOVA). 
-​
Homogeneity Test: Levene's test will be performed to ensure equal variances between groups. 
Covariates 
-​
Covariates such as age, initial body mass index (BMI), and baseline frailty severity will be 
considered in multivariate analyses (such as ANCOVA) to control for confounding variables that 
may influence the intervention efficacy results. 
 
2.4.2​
ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
The primary endpoint is the change in frailty score from baseline to week 8. Frailty status is measured 
using a validated frailty assessment instrument as specified in the protocol, and the outcome is 
calculated as the difference between post-intervention and baseline scores, with greater reductions 
indicating improvement. The frailty score is treated as a continuous (interval) variable and analyzed as a 
repeated measure. The primary analysis will be conducted using  Linear Mixed-Effects Models or 
repeated measures ANOVA, with the post-intervention frailty score as the dependent variable, study 
group (three parallel groups) as the fixed factor, and baseline frailty score as a covariate to improve 
precision and control for baseline differences. Results will be presented as adjusted means (least-squares 
means) with standard errors, adjusted mean differences between groups, and 95% confidence intervals, 
using a two-sided significance level of 0.05. Model assumptions will be assessed through residual 
diagnostics, and appropriate transformations or nonparametric sensitivity analyses will be applied if 
needed. The analysis will follow the Intention-to-Treat (ITT) principle, including all randomized 
participants according to their assigned groups. Missing data will be handled using multiple imputation 
under the missing-at-random assumption, with sensitivity analyses performed as appropriate. As only 
one primary endpoint is specified, no adjustment for multiplicity is required; however, post-hoc pairwise 
comparisons will apply Tukey or Bonferroni correction. 
2.4.3​
ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
All secondary endpoints are considered supportive and exploratory and will be analyzed independently 
of the primary frailty outcome. Physical function will be assessed using the Short Physical Performance 
Battery (SPPB; total score 0–12), mobility using the Timed Up and Go Test (TUG, seconds), body 
composition using bioelectrical impedance analysis (fat mass, fat-free mass, skeletal muscle mass, and 
phase angle), pulmonary function using peak expiratory flow (PEF, L/min), and inflammatory status using 
serum IL-6 and TNF-α measured by ELISA. All outcomes are treated as continuous variables and 
measured from baseline to week 8. Analyses will be conducted under the Intention-to-Treat (ITT) 
principle using Linear Mixed-Effects Models with study group and time as fixed effects and participant as 
a random effect, adjusting for age, sex, and baseline values of each outcome to achieve a parsimonious 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
28 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
model. Biomarker data (IL-6 and TNF-α) will be log-transformed if distributions are skewed. Results will 
be presented as adjusted means (LSMEANS) with standard errors and between-group differences with 
95% confidence intervals. Model assumptions will be assessed using residual diagnostics and normality 
tests; nonparametric alternatives or data transformation will be applied if required. Missing data will be 
handled using likelihood-based estimation inherent to mixed models under the assumption of missing at 
random, with sensitivity analyses performed for outliers, nonadherence, and loss to follow-up. 
 
2.4.4​
SAFETY ANALYSES 
 
Safety endpoints will be analyzed descriptively for all participants who receive at least one session of the 
study intervention or control activity (Safety Analysis Set). Adverse events (AEs) will be summarized using 
frequencies and percentages by study group and overall, without formal hypothesis testing. 
Treatment-emergent AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
and each AE will be counted once per participant per preferred term. AEs will be presented by System 
Organ Class (SOC) and preferred term, and further stratified by severity (mild, moderate, severe), 
relationship to the study intervention (related or not related), and expectedness. For each AE, the 
following information will be reported: onset date, resolution date, duration, severity grade, seriousness, 
relationship to the study intervention, expectedness, action taken, and outcome. Serious adverse events 
(SAEs) and AEs leading to premature discontinuation of the study intervention will be listed separately 
and summarized in dedicated tables. Changes in safety-related parameters from baseline, if applicable 
(e.g., vital signs or clinical observations), will be summarized using descriptive statistics and shift tables. 
All safety analyses and reporting will be consistent with the procedures and definitions described in 
Section 8.2, Safety and Other Assessments. 
 
2.4.5​
BASELINE DESCRIPTIVE STATISTICS 
 
Baseline characteristics of participants will be summarized by intervention group using descriptive 
statistics. Continuous variables (e.g., baseline frailty score, physical function measures, laboratory values) 
will be presented as means and standard deviations or medians and interquartile ranges, as appropriate 
based on data distribution. Categorical variables (e.g., age, sex, frailty category, comorbidities) will be 
summarized using frequencies and percentages. Comparability of intervention groups at baseline will be 
assessed descriptively; formal inferential statistical testing of baseline differences will not be performed, 
as any observed differences are assumed to be due to random variation. However, clinically relevant 
imbalances identified at baseline may be considered for inclusion as covariates in adjusted analyses. 
 
2.4.6​
PLANNED INTERIM ANALYSES  
 
No formal statistical interim analyses are planned for this study. Given the relatively short intervention 
period, modest sample size, and the low-risk nature of the study interventions (mind–body exercise and 
nutritional supplementation), interim analyses for efficacy, futility, or sample size re-estimation are 
considered not applicable. Safety will be monitored continuously throughout the study by the principal 
investigator and study clinicians through routine adverse event (AE) and serious adverse event (SAE) 
reporting, as described in Section 8. Any unexpected pattern of SAEs, a clustering of severe 
intervention-related AEs, or any event suggesting unacceptable risk to participants may prompt and 
safety review and temporary suspension of study intervention for the affected participant. Decisions 
regarding suspension or discontinuation will be based on clinical judgment rather than formal statistical 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
29 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
boundaries and will be reported to the appropriate ethics committee in accordance with institutional 
procedures.  
 
2.4.7​
SUB-GROUP ANALYSES 
 
Subgroup analyses of the primary endpoint (change in frailty score) will be conducted to explore 
whether the effect of the study intervention differs by key demographic characteristics, including age 
and sex. These subgroup analyses will be performed by including interaction terms between intervention 
group and the demographic variable (e.g., group × age, group × sex) within the same linear mixed-effects 
model used for the primary analysis. Results will be presented descriptively and inferentially as adjusted 
mean changes with 95% confidence intervals. These analyses are exploratory and not powered for 
definitive subgroup comparisons. Race/ethnicity-based analyses will not be performed, as the study 
population is expected to be relatively homogeneous with respect to race/ethnicity, and the sample size 
is insufficient to support meaningful or reliable comparisons across racial/ethnic subgroups. 
 
For secondary endpoints (physical function, mobility, body composition, pulmonary function, and 
inflammatory biomarkers), similar exploratory subgroup analyses by age and sex will be conducted using 
the same statistical framework as the main analyses (e.g., linear mixed-effects models or ANOVA, as 
appropriate). Interaction terms will be used to assess potential effect modification by demographic 
characteristics. Findings from these analyses will be interpreted cautiously as hypothesis-generating only, 
given the limited sample size and lack of adjustment for multiple comparisons. 
 
2.4.8​
TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
Individual participant data will not be listed by measure and time point. Study results will be presented 
in aggregate form using summary statistics (e.g., means, standard deviations, adjusted means, and 
confidence intervals) by study group and assessment time point to protect participant confidentiality. 
Individual-level data may be reviewed internally for data verification and monitoring purposes but will 
not be included in reports or publications. 
 
2.4.9​
EXPLORATORY ANALYSES. 
 
Exploratory analyses will be conducted to support interpretation of the primary and secondary outcomes 
and to generate hypotheses for future studies; however, they will not be used as confirmatory evidence 
of efficacy. All planned exploratory analyses will be prespecified in the protocol and interpreted 
descriptively without formal adjustment for multiplicity. 
 
3​
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
3.1​
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
3.1.1​
INFORMED CONSENT PROCESS 
 
3.1.1.1​
CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO PARTICIPANTS 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
30 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study intervention.  The following consent materials are submitted with this 
protocol. 
●​ Informed Consent Form: The main document covering 20 mandatory ethical elements (including 
confidentiality, right to withdraw, and emergency contact information). 
●​ Subject Information Sheet: Description of mind-body training procedures and dosage guidelines 
for Goldsure supplements. 
●​ Recruitment Materials: Research brochures and posters to be displayed in community health 
facilities/senior health posts (Posyandu). 
●​ Oral Explanation Script: A guideline for researchers to explain key points of the study to seniors. 
●​ Medical Data Use Permission Form: Permission to access medical records related to the 
participant's general health status. 
 
Given that the study population is elderly, the researchers provided the following adaptations to the 
materials: 
●​ Large Print Materials: All written documents should be in a minimum font size of 14-16 pt (Arial 
or Times New Roman) to facilitate participants with visual impairments. 
●​ Use of Witnesses: For participants with disabilities in writing or reading, the consent process will 
be conducted in the presence of an independent witness (family or community leader), and the 
participant will provide a thumbprint in lieu of a signature. 
●​ Language: Although official documents are in Indonesian, the researchers will provide staff 
fluent in the regional language (Javanese) to provide oral explanations for participants who are 
more comfortable communicating in that language. 
 
3.1.1.2​
CONSENT PROCEDURES AND DOCUMENTATION 
 
 
The informed consent process will begin before individuals agree to participate and will continue 
throughout the study. A consent form approved by the Ethics Committee (KEPK) will be provided to 
prospective participants for review. The researcher will verbally explain the study, including the 
mind-body exercise and nutritional supplementation procedures, and answer any questions that arise. 
The explanation will be provided in language easily understood by older adults (including Javanese, if 
necessary). Participants will be given the opportunity to discuss the information with their family or 
guardian before signing the document. Participants must be informed that participation is voluntary and 
they can withdraw at any time without prejudice. The researcher will document this process in source 
documents (including the date), and the form will be signed before participants undergo specific 
research procedures. Participants' well-being is protected by ensuring that consent to participate will not 
affect the quality of medical care they receive in the community. 
 
3.1.2​
STUDY DISCONTINUATION AND CLOSURE 
 
This study may be paused or terminated early if there is sufficient reasonable cause. Written notification 
documenting the reasons for the suspension or termination will be provided by the appropriate 
authorities to the study participants, investigators, funding agencies, and regulatory authorities. If the 
study is paused or terminated prematurely, the Principal Investigator (PI) will promptly inform the study 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
31 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
participants, the Health Research Ethics Committee (KEPK), and the sponsor, and provide the reasons for 
the decision. Participants will be contacted to receive information about changes to the visit schedule or 
other safety measures. Things that may lead to study termination or suspension include, but are not 
limited to: 
1.​ Safety Risk: The discovery of an unexpected, significant, or unacceptable risk to participants 
(e.g., severe musculoskeletal injury during exercise or serious metabolic side effects following 
supplementation). 
2.​ Clear Efficacy: The evidence for the benefit of the intervention is so strong that it would be 
ethically unfair to immediately deprive the control group of the same benefit. 
3.​ Protocol Non-Compliance: Inadequate adherence to protocol requirements that compromises 
participant safety or data validity. 
4.​ Data Integrity: Data collected are incomplete or unsuitable for statistical evaluation. 
5.​ Futility: Determination that the primary objective of the study (frailty improvement) is unlikely 
to be achieved even if the study continues. 
6.​ Institutional Decision: Termination based on the discretion of the Ethics Committee or relevant 
health authority. 
The study may be resumed after concerns regarding safety, protocol compliance, and data quality have 
been fully resolved and written approval from the KEPK and the Sponsor has been obtained. 
 
 
3.1.3​
CONFIDENTIALITY AND PRIVACY  
 
The Principal Investigator, research staff, and the host institution strictly maintain the confidentiality and 
privacy of participants. All clinical data, physical examination results, and biological sample test results 
(such as albumin/protein levels) will be treated as strictly confidential. The study protocol, 
documentation, data, and all resulting information will be stored securely. No information regarding the 
study or participant data will be shared with unauthorized third parties without prior written permission 
from the investigator or sponsor. Research data will not be directly associated with participants' personal 
identification (such as full names or addresses). Files will be stored in a coded system. Physical data, 
including paper, questionnaires, and study medical records, will be stored in a filing cabinet. Data for 
statistical analysis will be entered into a password-protected electronic database. Only de-identified 
(anonymous) data will be used for analysis. In accordance with institutional policy, all research records 
will be retained for a minimum of 5 years after completion of the study, after which the physical data will 
be destroyed and the digital data will be permanently deleted. Access to the original research data will 
be granted to the principal investigator and research assistants. Research results will be published in 
scientific journals or presented in academic forums. In all publications, data will be presented in 
aggregate form. No individual identifiers, uncensored facial photographs, or family details will be 
published, making it impossible for readers to identify specific participants. If data must be shared with 
researchers outside the team (e.g., for meta-analyses), only anonymized data will be submitted. 
 
3.1.4​
FUTURE USE OF STORED SPECIMENS AND DATA  
 
All data (questionnaires, physical test results, video recordings/photographs) and biological samples 
(blood for albumin/protein testing) collected in this study will be used solely for the purpose of this 
study, namely to evaluate the effectiveness of Mind-Body Exercise and nutritional supplementation on 
frailty. 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
32 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
No data or samples will be used for any other future secondary research. Once all data analysis for this 
study is completed and the research results are published, the physical data will be destroyed (shredded) 
after the institution's mandatory retention period (minimum 5 years) has been met. All remaining blood 
samples will be immediately destroyed in accordance with laboratory medical waste procedures 
immediately after the research parameters (albumin/protein) have been analyzed. No samples will be 
stored long-term (biobanking). 
 
The researcher guarantees that all data collection, processing, and analysis will be conducted entirely 
within the jurisdiction of the Republic of Indonesia. No biological samples (blood) or raw participant 
identity data will be sent abroad. Collaboration with foreign researchers is limited to methodology 
consultation and instrument validation. Data shared with international collaborators (if any) is only 
aggregate/group statistically processed data, not individual data, so that participant confidentiality and 
national data sovereignty are fully maintained. Video recordings or photos taken during the Mind-Body 
Exercise training sessions are only used to verify compliance with the exercise protocol by the research 
team. These recordings will be permanently deleted immediately after the data verification process is 
complete and will not be published in any media without strict facial censorship and additional written 
permission from the participants. 
 
3.1.5​
KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator 
Medical Monitor 
Rista Fauziningtyas, S.Kep., Ns., 
M.Kep, PhD 
Nanda Aulya Ramadhan, dr. 
Faculty of Nursing, Airlangga 
University  
General Hospital Universitas 
Airlangga  
Kampus C Mulyorejo, Surabaya, 
60115 
Jl. Dr. Ir. H. Soekarno, Mulyorejo, 
Kec. Mulyorejo, Kota SBY, Jawa 
Timur 60115 
081330718027 
081388372132 
ristafauziningtyas@fkp.unair.ac.id 
nanda.aulya.r@fk.unair.ac.id 
 
 
3.1.6​
SAFETY OVERSIGHT 
An independent Data and Safety Monitoring Board (DSMB) will not be established for this study. Data 
safety and integrity oversight will be conducted internally by the core research team using the following 
procedures: 
●​ The Principal Investigator (PI), along with the Medical Monitor, will be solely responsible for the 
daily monitoring of participant safety. The Medical Monitor will review any Adverse Events (AD) 
reported by the nurses or research assistants in the field related to the Mind-Body Exercise 
intervention and nutritional supplementation. 
●​ Data safety reviews will be conducted periodically at weekly research team meetings. The 
Principal Investigator will review: Reports of participants' physical complaints after the exercise 
sessions.  
●​ Records of participants' tolerance to nutritional supplements. 
●​ Participants' adherence to the study protocol. 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
33 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
●​ Although there is no independent board, the Principal Investigator will conduct a formal 
evaluation midway through the study (week 12) to assess any unforeseen risks to participants. If 
the risk is found to be significant, the Principal Investigator has the authority to temporarily 
suspend the study and is required to report it to the Health Research Ethics Committee (KEPK) of 
the Faculty of Nursing, Airlangga University within 24 hours to obtain further direction. 
3.1.7​
CLINICAL MONITORING 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of the 
trial is in compliance with the currently approved protocol. 
Internal monitoring for this study will be performed by members of the research team designated by the 
Principal Investigator (PI) to maintain objectivity and minimize bias. 
Monitoring will consist of a combination of on-site visits and centralized data reviews: 
●​ On-site Monitoring: Internal monitors will visit each community site (Puskesmas/Posyandu) at 
the beginning of the study (Initiation Visit) to ensure all staff have been properly trained. 
●​ Centralized Monitoring: Monthly reviews of the electronic database will be conducted to identify 
missing data, outliers, or inconsistencies in frailty assessment scores and nutritional intake logs. 
The extent of monitoring will include: 
●​ Comprehensive (100%) Verification: All Informed Consent Forms, participant eligibility criteria 
(inclusion/exclusion), and any reported Adverse Events (AEs) will be verified against source 
documents. 
●​ Targeted Verification (at least 20%): A random review of 20% of the primary endpoint data (e.g., 
frailty scores, handgrip strength, gait speed) and nutritional supplement (Goldsure) 
accountability records will be performed to ensure data integrity. 
Monitoring reports summarizing findings and any required corrective actions will be distributed to the 
Principal Investigator (PI) within 7 days of each visit. Any critical deviations from the protocol will be 
addressed immediately and documented. 
Routine independent audits by external parties will not be conducted; however, the research team will 
maintain all study records in a state of audit-readiness should the Health Research Ethics Committee 
(KEPK) or local health authorities choose to conduct an inspection at any time. 
3.1.8​
QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will implement internal quality management for study implementation, data and 
biological specimen collection, documentation, and completion. An individual quality management plan 
will be developed to outline the quality management for each site. 
●​ To maintain data consistency across groups (to prevent bias), the principal investigator will 
conduct standardized training for all research staff, volunteers, and nurses before the study 
begins. The training will cover exercise procedures, proper nutritional supplement consumption, 
and side effect management. Prior to baseline data collection, a calibration exercise will be 
conducted among research assistants for physical measurements (SPPB score, gait speed, and 
handgrip strength). This ensures that variations in results are due to the intervention's effects, 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
34 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
not differences in measurement techniques among staff. Each research assistant is required to 
participate in this activity, and proof of attendance will be recorded in the exercise log as part of 
the quality record. 
●​ Quality assurance and standard operating procedures (SOPs) refer to written Standard Operating 
Procedures (SOPs). Researchers will ensure that: The mind-body exercise intervention is carried 
out according to the module by trained nurses, volunteers, and research assistants; the 
distribution of nutritional supplements must be recorded to compare the dispensed stock with 
the participant's intake diary; and blood samples are collected and processed according to 
standards. 
●​ The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities 
 
3.1.9​
DATA HANDLING AND RECORD KEEPING 
 
3.1.9.1​
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
Principal Investigator (PI). The PI is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the reported data. 
All source documents must be completed in a neat and legible manner to ensure accurate data 
interpretation. Hard copies of the study visit worksheets will be provided for use as source document 
worksheets to record data for each participant enrolled in the study (Combination Group, Exercise-only 
Group, and Control Group). 
Source documents in this study include: 
●​ Physical measurement worksheets (gait speed, handgrip strength, SPPB scores). 
●​ Frailty assessment and nutritional intake questionnaires. 
●​ Daily consumption logs for supplementation. 
●​ Printed laboratory results for clinical data. 
Data recorded in the electronic Case Report Forms (eCRF) derived from source documents must be 
consistent with the data recorded on the original source documents. Clinical data (including Adverse 
Events (AEs), concomitant medications, and expected adverse reactions) as well as clinical laboratory 
data will be entered into the data system. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the physical source documents by designated 
research assistants. 
To ensure participant safety, study participation will be formally recorded in the participants' medical 
records or health books at the local Puskesmas (Public Health Center). This ensures that other healthcare 
providers accessing the participant's medical records have adequate knowledge that the participant is 
involved in a clinical trial for physical and nutritional intervention. 
Data handling responsibilities consist of: 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
35 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
●​ Research Staff: Responsible for daily data entry and ensuring the legibility of physical 
documents. 
●​ Principal Investigator: Performs weekly reviews of the eCRF to ensure timeliness of submission 
(no later than 48 hours after the visit). 
●​ Storage: All physical source documents will be stored in a secure, locked cabinet, and electronic 
data will be backed up regularly to prevent data loss. 
 
3.1.9.2​
STUDY RECORDS RETENTION  
Study documents will be retained for a minimum period of 3 years after the research is completed. The 
retained documents include the original consent form, physical data worksheets, supplement 
distribution records, and laboratory results. Considering that the sponsor/product provider has no 
interest or ownership rights over this research data, all control over the integrity and confidentiality of 
the documents is under the full responsibility of the Principal Investigator (PI). The researcher will ensure 
the security of the documents by entering a predetermined code or password. After a long period of 
time has expired, the researcher will extend the data. 
 
3.1.10​ PROTOCOL DEVIATIONS  
A protocol deviation is any form of non-compliance with the approved clinical trial protocol. This 
non-compliance can originate from participants, investigators, or field staff. 
The Principal Investigator (PI) is responsible for continuously monitoring and identifying any deviations. 
All deviations must be documented in source documents and reported to the Health Research Ethics 
Committee (KEPK) in accordance with applicable policies. 
If a deviation is discovered (such as participant non-attendance at exercise sessions or non-compliance 
with nutritional intake), the research team will promptly develop and implement corrective actions. Each 
deviation will be evaluated to determine its impact on data integrity and participant safety. 
 
3.1.11​ PUBLICATION AND DATA SHARING POLICY 
This research will be conducted in accordance with the publication and dissemination policies of 
scientific information applicable to the Faculty of Nursing, Airlangga University, and international 
standards. 
●​ This study will be registered on international and national clinical trial registration portals 
(Clinicaltrial.gov and INA-CRR) before participant recruitment begins. The final results of this 
clinical trial will also be reported on these portals after the study is completed. 
●​ Every effort will be made to publish the results of this study in a reputable, peer-reviewed 
international journal. Authorship will be determined based on substantial contributions to study 
design, data collection, or data analysis, in accordance with the International Committee of 
Medical Journal Editors (ICMJE) guidelines. 
●​ Data generated from this study may be requested by other researchers for scientific purposes 
after a minimum of two years from the publication of the primary results. Data requests can be 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
36 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
submitted by contacting the Principal Investigator (PI) and must include a clear analysis protocol 
and ethical approval from the requesting institution. 
 
3.1.12​ CONFLICT OF INTEREST POLICY 
The Principal Investigator and all research staff declare that they have no financial or personal conflicts 
of interest in conducting this research. The independence of this research from industry influence is 
strictly maintained to ensure scientific integrity. 
The product provider had no role in the study design, data collection, statistical analysis, interpretation 
of results, or the decision to publish the manuscript. All members of the research team have signed a 
written statement confirming that they have no conflict of interest that could affect the objectivity of the 
research. All forms of support received for this research (such as institutional grants) have been 
transparently disclosed and have no strings attached to the research results. 
3.2​
ADDITIONAL CONSIDERATIONS 
 
N/A 
 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
37 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
3.3​
ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSOR
T 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 
2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
38 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
39 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
3.4​
PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
40 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
41 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
4​
REFERENCES  
[1]​ A. A. Pradana, H. L. Chiu, C. J. Lin, and S. C. Lee, “Prevalence of frailty in Indonesia: a 
systematic review and meta-analysis,” BMC Geriatr., vol. 23, no. 1, pp. 1–14, 2023, doi: 
10.1186/s12877-023-04468-y. 
[2]​ S. Sourdet, B. Vellas, and F. Forette, “Frailty and aging,” J. Nutr. Health Aging, vol. 16, no. 
4, 2011. 
[3]​ R. O’Caoimh et al., “Prevalence of frailty at population level in European ADVANTAGE 
Joint Action Member States: A systematic review and meta-analysis,” Ann. Ist. Super. 
Sanita, vol. 54, no. 3, pp. 226–238, 2018. 
[4]​ T.-L. To, T.-N. Doan, W.-C. Ho, and W.-C. Liao, “Prevalence of Frailty among 
Community-Dwelling Older Adults in Asian Countries: A Systematic Review and 
Meta-Analysis,” Healthc., vol. 10, no. 5, 2022, doi: 10.3390/healthcare10050895. 
[5]​ A. Rizka, A. Indrarespati, N. Dwimartutie, and M. Muhadi, “Frailty among older adults 
living in nursing homes in indonesia: Prevalence and associated factors,” Ann. Geriatr. 
Med. Res., vol. 25, no. 2, pp. 93 – 97, 2021, doi: 10.4235/agmr.21.0033. 
[6]​ M. S. Song and S. Boo, “Effects of a nurse-led multicomponent intervention for frail older 
adults living alone in a community: a quasi-experimental study,” BMC Nurs., vol. 21, no. 1, 
pp. 1–9, Jan. 2022, doi: 10.1186/s12912-021-00801-1. 
[7]​ A. S. Kasa, P. Drury, V. Traynor, S.-C. Lee, and H.-C. (Rita) Chang, “The effectiveness of 
nurse-led interventions to manage frailty in community-dwelling older people: a systematic 
review,” Syst. Rev., vol. 12, no. 1, 2023, doi: 10.1186/s13643-023-02335-w. 
[8]​ G. Kang, H. Ji, and J. Y. Yoon, “The effect of community health nurse-led multi-faceted 
group-based frailty prevention program for older adults: a multi-site pretest-posttest 
design,” BMC Nurs., vol. 24, no. 1, 2025, doi: 10.1186/s12912-025-03372-7. 
[9]​ R. Yu, C. Tong, F. Ho, and J. Woo, “Effects of a Multicomponent Frailty Prevention Program 
in Prefrail Community-Dwelling Older Persons: A Randomized Controlled Trial,” J. Am. 
Med. 
Dir. 
Assoc., 
vol. 
21, 
no. 
2, 
pp. 
294.e1-294.e10, 
Feb. 
2020, 
doi: 
10.1016/j.jamda.2019.08.024. 
[10]​L. F. Tan et al., “Impact of Exercise and Cognitive Stimulation Therapy on Physical 
Function, Cognition and Muscle Mass in Pre-Frail Older Adults in the Primary Care 
Setting: A Cluster Randomized Controlled Trial,” J. Nutr. Heal. Aging, vol. 27, no. 6, pp. 
438–447, 2023, doi: 10.1007/s12603-023-1928-7. 
[11]​S. Setiati et al., “Frailty state among Indonesian elderly: Prevalence, associated factors, 
and frailty state transition,” BMC Geriatr., vol. 19, no. 1, pp. 1–10, 2019, doi: 
10.1186/s12877-019-1198-8. 
[12]​K. Kavita, J. S. Thakur, S. Ghai, T. Narang, and R. Kaur, “Nurse - led interventions for 
prevention and control of noncommunicable diseases in low - and middle - income 
countries : A systematic review and meta - analysis,” Int. J. Noncommunicable Dis., pp. 
4–13, 2023, doi: 10.4103/jncd.jncd. 
[13]​M. S. Song and S. Boo, “Effects of a nurse-led multicomponent intervention for frail older 
adults living alone in a community: a quasi-experimental study,” BMC Nurs., vol. 21, no. 1, 
2022, doi: 10.1186/s12912-021-00801-1. 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
42 

<Protocol Title>​
Version <x.x> 
Protocol <#>​
<DD Month YYYY> 
[14]​ J. Barrachina-Igual, F. M. Martínez-Arnau, P. Pérez-Ros, C. Flor-Rufino, R. Sanz-Requena, 
and A. Pablos, “Effectiveness of the PROMUFRA program in pre-frail, community-dwelling 
older people: A randomized controlled trial,” Geriatr. Nurs. (Minneap)., vol. 42, no. 2, pp. 
582–591, Mar. 2021, doi: 10.1016/j.gerinurse.2020.10.014. 
[15]​R. Radaelli et al., “Effects of Resistance Training Volume on Physical Function, Lean Body 
Mass and Lower-Body Muscle Hypertrophy and Strength in Older Adults: A Systematic 
Review and Network Meta-analysis of 151 Randomised Trials,” Sport. Med., vol. 55, no. 1, 
pp. 167–192, 2025, doi: 10.1007/s40279-024-02123-z. 
[16]​H. Wang, Y. Liang, H. Wu, H. Shi, and R. Hou, “Effect of multicomponent exercise 
intervention in community dwelling frail elderly: A systematic review and meta-analysis,” 
Arch. Gerontol. Geriatr., vol. 126, 2024, doi: 10.1016/j.archger.2024.105543. 
[17]​I. Rodríguez-Gómez et al., “Relationship between physical performance and frailty 
syndrome in older adults: The mediating role of physical activ-ity, sedentary time and body 
composition,” Int. J. Environ. Res. Public Health, vol. 18, no. 1, pp. 1–12, Dec. 2021, doi: 
10.3390/ijerph18010203. 
[18]​A. Hendry, R. O’Caoimh, M. A. Salem, A. Carriazo, and R. Roller-Wirnsberger, Integrated 
Care for Frailty. 2024. doi: 10.1007/978-3-031-57361-3_31. 
[19]​J. Pöyhönen et al., “Impact of frailty status on the effect of a multidomain lifestyle 
intervention on cognition,” Age Ageing, vol. 54, no. 2, 2025, doi: 10.1093/ageing/afaf041. 
[20]​G. Maiden, A. Kingsford, A. P. Wang, A. R. Tran-Nam, and J. Nelson, “Reimagining Day 
Rehabilitation For Frailty and Neurodegenerative Conditions through the integrated 
Rehabilitation and EnAblement Program (iREAP),” Int. J. Integr. Care, vol. 24, no. 3, 2024, 
doi: 10.5334/ijic.8066. 
[21]​É. Ní Shé et al., “The systematic approach to improving care for Frail Older Patients 
(SAFE) study: A protocol for co-designing a frail older person’s pathway,” HRB Open 
Researc, vol. 1, no. 9, 2018. 
[22]​M. McDonnell, M. Bell, F. Lawler, A. Duffy, and M. Connolly, “Multidisciplinary Inpatient 
Community Rehabilitation Programmes for Frail Older People: A Scoping Review,” Nurs. 
Open, vol. 11, no. 11, 2024, doi: 10.1002/nop2.70088. 
[23]​A. A. Kjelsnes and E. Feiring, “Models of integrated care for older people with frailty: a 
horizon 
scanning 
review,” 
BMJ 
Open, 
vol. 
12, 
no. 
4, 
2022, 
doi: 
10.1136/bmjopen-2021-060142. 
[24]​L. Lippi et al., “Closing the Gap between Inpatient and Outpatient Settings: Integrating 
Pulmonary Rehabilitation and Technological Advances in the Comprehensive Management 
of Frail Patients,” Int. J. Environ. Res. Public Health, vol. 19, no. 15, 2022, doi: 
10.3390/ijerph19159150. 
[25]​Lembaga Penelitian dan Pengabdian Universitas Airlangga, “Rencana Induk Penelitian 
(RIP) Universitas Airlangga Tahun 2022-2026,” 2021, Airlangga University Press, 
Surabaya. 
 
 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017​
​
43