Efficacy Test of Curcuminoid Standardized Turmeric Capsules to Improving Inflammatory Biomarkers in Osteoarthritis Genu
Phase: PHASE2
Conditions: Osteoarthritis
Sponsor: Gadjah Mada University

Protocol No. 055/20/VI/EC/KEPK-3/STIKES RSBK/2025 
Date: 20/07/2025 
Efficacy Test of Curcuminoid Standardized Turmeric Capsules to Improving Inflammatory 
Biomarkers in Osteoarthritis Genu 
Page 1  
 
 
Cover 
 
 
 
Efficacy Test of Curcuminoid Standardized Turmeric Capsules 
to Improving Inflammatory Biomarkers in Osteoarthritis Genu   
 
 
 
 
 
 
 
 
 
 
Investigator 
Srinalesti Mahanani 
Nyoman Kertia 
Desi Natalia Trijayanti Idris 
Erlin Kurnia 
 
 
 
 
 
 
KEDIRI BAPTIST HEALTH SCIENCE COLLEGE 
INDONESIA 
 
 

Protocol No. 055/20/VI/EC/KEPK-3/STIKES RSBK/2025 
Date: 20/07/2025 
Efficacy Test of Curcuminoid Standardized Turmeric Capsules to Improving Inflammatory 
Biomarkers in Osteoarthritis Genu 
Page 2  
 
 
Table of contents 
Table of Contents 
Cover ................................................................................................................................................ 1 
Table of Contents ...................................................................................................................... 2 
Protocol summary ...................................................................................................................... 4 
1 
Introduction ............................................................................................................................... 6 
1.1 
Background .................................................................................................................... 6 
1.2 
Purpose .......................................................................................................................... 7 
2 
Study objectives and endpoints ................................................................................................. 7 
2.1 
Primary Objective .......................................................................................................... 7 
2.2 
Secondary Objectives .................................................................................................... 7 
3 
Investigational Plan ................................................................................................................... 7 
3.1 
Study Design .................................................................................................................. 7 
3.2 
Study setting and source population .............................................................................. 7 
4 
Population .................................................................................................................................. 7 
4.1 
Inclusion Criteria ........................................................................................................... 8 
4.2 
Exclusion Criteria .......................................................................................................... 8 
4.3 
Eligibility Test Procedure .............................................................................................. 8 
5 
Randomization, allocation, and blinding ................................................................................... 9 
6 
Intervention .............................................................................................................................. 11 
7 
Outcomes ................................................................................................................................. 11 
Primary Outcomes measures ................................................................................................... 11 
Secondary outcomes ................................................................................................................ 12 
8 
Statistical Issues ....................................................................................................................... 12 
Sample size .............................................................................................................................. 12 
9 
Protection of Human Subjects and Assessment of Safety ....................................................... 12 
9.1 Protection of Participants .................................................................................................. 12 
9.2 Adverse Events .................................................................................................................. 12 
9.3 Data Analysis ..................................................................................................................... 12 
9.4 Data Management .............................................................................................................. 13 
10. Ethical considerations .............................................................................................................. 13 
10.1 
Regulatory and Ethical Compliance ............................................................................ 13 
10.2 
Informed Consent Procedures ...................................................................................... 13 
10.3 
Responsibilities of the investigator and IRB/IEC ........................................................ 13 

Protocol No. 055/20/VI/EC/KEPK-3/STIKES RSBK/2025 
Date: 20/07/2025 
Efficacy Test of Curcuminoid Standardized Turmeric Capsules to Improving Inflammatory 
Biomarkers in Osteoarthritis Genu 
Page 3  
 
10.4 
Publication of study protocol and results ..................................................................... 14 
11. Protocol adherence .................................................................................................................. 14 
11.1 
Protocol amendments................................................................................................... 14 
12. References ............................................................................................................................... 14 

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Protocol No. 055/20/VI/EC/KEPK-3/STIKES RSBK/2025 
Date: 20/07/2025 
Efficacy Test of Curcuminoid Standardized Turmeric Capsules to Improving Inflammatory 
Biomarkers in Osteoarthritis Genu 
 
 
 
 
 
Protocol summary 
Unique Protocol ID 
055/20/VI/EC/KEPK-3/STIKES RSBK/2025 
Title 
Efficacy Test of Curcuminoid Standardized Turmeric Capsules to 
Improving Inflammatory Biomarkers in Osteoarthritis Genu 
Brief title 
Efficacy Test of Curcuminoid Standardized Turmeric Capsules to 
Improving Biomarkers in Osteoarthritis Genu 
Sponsor and Clinical 
Phase 
Ministry of Higher Education Science and Technology 
Investigation type 
Drug 
Study type 
Interventional 
Purpose and rationale 
Evaluate the efficacy, safety, and tolerability of standardized curcuminoid 
from turmeric extract to TNF-Alpha, Interleukin-1 and CRP in elderly 
patients with Osteoarthritis Genu. 
Primary Objective(s) 
To determine the effectiveness of curcuminoid as measured by changes 
from baseline (BL) in TNF-Alpha, Interleukin-1 and CRP in the blood to 
placebo after three weeks of treatment in elderly patients with 
Osteoarthritis 
Secondary Objectives 
To evaluate the effect of acupressure and standardized curcuminoid from 
turmeric extract vs placebo at three weeks : Knee pain as measured by 
the VAS score  
Study design 
Randomized controlled trial, double-blind to assess efficacy, tolerability, 
and safety curcuminoid versus placebo. Patients can be pre-screened for 
specific x-ray and laboratory parameters. Eligible subjects will enter the 
washout for one week following a screening visit. After the washout 
period, eligible subjects will be randomized and treated for three weeks. 
The total duration of the study is up to 5 weeks. 
Population 
Approximately 60 female and male patients ≥ 65 years old 
Key Inclusion criteria 
• 
Clinical diagnosis of Osteoarthritis, which was confirmed by physical 
examination and X-rays 
• 
Experience pain with a Numeric Rating scale of 1-7 
• 
Must be able to swallow capsules 
• 
Must be able to carry out mobility without assistance or with minimal 
assistance 

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Protocol No. 055/20/VI/EC/KEPK-3/STIKES RSBK/2025 
Date: 20/07/2025 
Efficacy Test of Curcuminoid Standardized Turmeric Capsules to Improving Inflammatory 
Biomarkers in Osteoarthritis Genu 
 
 
 
Key Exclusion criteria • 
Parkinson's disease  
• 
Dementia disease 
• 
Psychosis  disease 
• 
Fractures 
• 
Joint dislocations 
• 
Cancer 
• 
Rheumatic diseases other than Osteoarthritis (rheumatoid arthritis) 
• 
Undergoing joint replacement therapy. 
• 
Analgesic dependent disease 
Study treatment 
• 
Combination of Acupressure and Curcuminoid from turmeric extract 
• 
Placebo 
Efficacy assessments • 
TNF-Alpha 
• 
Interleukin-1  
• 
C-Reactive Protein 
Key safety assessment • 
Physical examination 
• 
Vital signs 
• 
Monitoring of laboratory markers in blood 
Others assessment 
• 
Knee pain 
Data analysis 
The primary efficacy variable is the number of TNF-Alpha, Interleukin-1 
and CRP in blood, collected at Week 4 to BL (i.e., change from BL in the 
number of Leukocytes at Week 4). It will be analyzed using the Wilcoxon 
signed-rank test or paired t-test and the Mann-Whitney U test or 
independent t-test. The significance level will be set at 0.05. All outcome 
measures will be recorded at baseline and after two weeks of intervention 
Keywords 
Osteoarthritis, 
curcuminoid, 
randomized 
control trial, 
TNF-Alpha, 
Interleukin-1 

Page 6 
 
Protocol No. KE_FK_0674_EC_2023 
Date: 06/10/2023 
Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins, and Quality of Life in Elderly People With Osteoarthritis Genu   
 
 
 
 
1 
Introduction 
1.1 
Background 
One of the degeneration processes that occurs in the elderly is the musculoskeletal system. 
These deteriorations include bone loss and decreased joint fluid volume exacerbated by bearing 
the body's weight. This deterioration causes elderly people to experience pain. The experience 
of prolonged pain in Osteoarthritis patients becomes a “ Breakpoint," which centers on the 
experience/process of living with unremitting pain, limitations in mobility, leisure, and social 
activities, and the resulting consequences for the patient's physical and psychological well-
being. The breakpoint experienced by Osteoarthritis patients is the turning point for changes in 
the quality of life in Osteoarthritis. Popular alternative therapies include herbal therapy, 
therapeutic touch, relaxation techniques, music therapy, acupuncture, and acupressure. One of 
the therapies very close to the community, especially the Javanese, is acupressure, a further 
development of massage. Until now, massage is an action that people often do independently 
and can psychologically make patients feel comfortable, but research needs to continue to be 
carried out to ensure its effectiveness. 
Pain in Osteoarthritis patients affects many areas of quality of life, such as physical function, 
emotional behavior, and mental health. Osteoarthritis-related pain is a major factor in poor 
quality of life. The most common pharmacological treatment to control pain is using non-
steroidal anti-inflammatory drugs (NSAIDs), but these drugs risk causing side effects. 
Limitations associated with pharmacologic treatment result in patients choosing commonly 
available alternative therapies for pain management. Popular alternative therapies include 
herbal therapy, therapeutic touch, relaxation techniques, music therapy, acupuncture, and 
acupressure. Unlike the use of drugs, this alternative therapy does not produce dangerous side 
effects. (Li et al., 2018) 
Research on the effectiveness of herbal therapy on inflammatory osteoarthritis patients was 
conducted in Indonesia by Kertia in 2009 on 80 sufferers with the result that administration of 
turmeric rhizome extract curcuminoids significantly suppressed the activity of synovial fluid 
monocytes to secrete COX-2 and ROI, reduced leukocyte numbers and fluid MDA levels. 
Synovia reduces OA joint pain, with an ability that is not significantly different compared to 
diclofenac sodium therapy 3x25 mg per day (Kertia, 2009). Furthermore, the development of 
herbal therapy for Osteoarthritis continued with research by Bertorio (Bertorio, 2017) which 
proved that the combination of ginger, ginger, soybean and shrimp shell extracts provided 
significant results in reducing joint pain, stiffness and physical disability which were evaluated 
based on the Western Ontario and McMaster values. Universities Osteoarthritis Index 
(WOMAC) did not show a significant difference when compared with meloxicam. 
Research that has been carried out to evaluate the effectiveness of acupressure therapy for the 
pain of Osteoarthritis patients was also carried out in several countries, including by 
Alinaghizadeh on 40 Osteoarthritis patients who were divided into two groups (intervention and 
control). In the intervention group, acupressure therapy was given for 5 days for 30 minutes 
each time. The results showed that the average pain score in the intervention group decreased 
significantly from 5.89 at the beginning to 4.11 at the end of the study, while the pain score did 
not change substantially in the control group. These findings remained consistent after age, 
weight, and pretreatment covariates were adjusted. This study supports the evidence that 
Acupressure therapy provides an effective option for short-term knee pain relief in patients with 
knee Osteoarthritis. (Maryam Alinaghizadeh et al., 2021). In line with the results of 
Alinaghizadeh's research, there was research conducted by Akbarnezhad (Akbarnezhad et al., 
2019) which was conducted on 51 elderly with Osteoarthritis divided into 3 groups (acupressure 
intervention, placebo and control). This study revealed that respondents who received 
acupressure therapy for 3-4 weeks with the duration of each therapy being 10-15 minutes, 

Page 7 
 
Protocol No. KE_FK_0674_EC_2023 
Date: 06/10/2023 
Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins, and Quality of Life in Elderly People With Osteoarthritis Genu   
 
showed a significant reduction in the total WOMAC index, pain and physical dysfunction. 
So far, no research has been combining standardized curcuminoid turmeric extract therapy with 
acupressure for inflammation and pain in osteoarthritis patients. More clinical trials with 
appropriate methodology are needed to confirm the effectiveness of standardized turmeric 
extract, curcuminoids and acupressure to treat physical problems in osteoarthritis patients. 
 
1.2 
Purpose 
To investigate the efficacy of standardized curcuminoids from turmeric extract to TNF-Alpha, 
Interleukin-1 and CRP in the blood and pain in elderly patient with Osteoarthritis Genu. 
 
2 
Study objectives and endpoints 
2.1 
Primary objective 
To determine the effectiveness of combination two regimens (acupressure and curcuminoid) as 
measured by changes from baseline (BL) in TNF-Alpha, Interleukin-1 and CRP in blood to 
placebo after 3 weeks of treatment in elderly patients with Osteoarthritis 
 
2.2 
Secondary objectives 
To evaluate the effect of acupressure and standardized curcuminoid from turmeric extract vs 
placebo at 3 weeks is Knee Pain that were measured by VAS 
3 
Investigational plan 
3.1 
Study design 
Randomized controlled trial, we will conduct a 2-arm, double-blind (patient and investigational 
blinded) to assess efficacy, tolerability and safety curcuminoid versus placebo. 
 
Pre-Screening:   
Patients can be pre-screened for specific x-ray and laboratory parameters. Following a screening 
visit, eligible subjects will enter the washout. After the washout period, eligible subjects will be 
randomized and treated for 3 weeks. The total duration of the study is up to 5 weeks. 
3.2 
Study setting and source population 
 
Eligible participants were individuals recruited from communities covered by government-
owned primary care hospitals who consulted a rheumatology subspecialist physician with 
symptoms of pain and discomfort around the knee. 
Participants will be recruited from June 2025 to September 2025. An informed consent form will 
be provided to participants in their local language to gain credibility. Codes will be assigned to 
ensure confidentiality for data collection, with only the primary researcher having access to the 
participant codes for each group. Participants providing their consent will be further screened for 
eligibility. 
 
4 
Population 
The study population will consist of male and female patients (≥65 years old) with Osteoarthritis 
(Osteoarthritis with knee joint pain, knee joint stiffness in the morning less than 30 minutes, 
Crepitus, deformity, joint swelling (right and left asymmetrical), Other signs of inflammation 
(a feeling of even warmth and reddish color). The goal is to randomize a total of approximately 
60 patients. Since a 25% screening failure rate and a 20% washout failure rate is expected, 

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Protocol No. KE_FK_0674_EC_2023 
Date: 06/10/2023 
Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins, and Quality of Life in Elderly People With Osteoarthritis Genu   
 
approximately 100 patients will be screened. 
 
4.1 
Inclusion criteria 
Patients eligible for inclusion in this study must fulfill all of the following criteria: 
1. Clinical diagnosis of Osteoarthritis which confirmed by physical examination and x-rays 
2. Experience pain with a Numeric Rating scale of 1-7 
3. Must be able to swallow capsules 
4. Must be able to carry out mobility without assistance or with minimal assistance 
 
 
4.2 
Exclusion criteria 
Patients fulfilling the following criteria are not eligible for inclusion in this study. The 
investigator may apply no additional exclusions to ensure the study population represents all 
eligible patients. 
1. Parkinson's disease  
2. Dementia disease 
3. Psychosis  disease 
4. Fractures 
5. Joint dislocations 
6. Cancer 
7. Rheumatic diseases other than Osteoarthritis (rheumatoid arthritis) 
8. Undergoing joint replacement therapy. 
9. Analgesic dependent disease 
 
4.3 
Eligibility test procedure 
Radiographs will be used to assess participants for Osteoarthritis using the Kellgren and Lawrence 
criteria which divide Osteoarthritis from mild to severe. It should be remembered that at the 
beginning of the disease, the radiographic appearance of the joint still looks normal. According to 
Kellgren and Lawrence, radiologically, Osteoarthritis is classified as follows:  
1) Grade 0: Normal, no signs of Osteoarthritis 
2) Grade 1: Doubtful, without osteophytes, doubtful joint narrowing 
3) Grade 2: Minimal, few osteophytes on the tibia and patella and the joint surface is 
asymmetrically narrowed. 
4) Grade 3: Moderate, moderate osteophytes are in several places, the joint surface is narrowed, and 
subchondral sclerosis appears. 
5) Grade 4: Severe, presence of large osteophytes, complete narrowing of the joint surface, severe 
subchondral sclerosis, and joint surface damage. 

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Protocol No. KE_FK_0674_EC_2023 
Date: 06/10/2023 
Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins, and Quality of Life in Elderly People With Osteoarthritis Genu   
 
The Mini Mental State Examination (MMSE) test will assess the patient's cognitive abilities, whichi 
is essential to ensure that patients can understand the treatment and outcome measurement process 
instructions.  
5 
Randomization, allocation and blinding 
60 eligible participants will be randomized to the group with curcuminoid capsules (C; group 1) or 
the group with placebo (P; group 2) via lottery randomization. After that subjects will be randomly 
allocated to C and P group. The schematic CONSORT (Consolidated Standards of Reporting 
Trials) flow diagram for the study protocol is presented in Figure 1—Schematic CONSORT 
(Consolidated Standards of Reporting Trials) flowchart for the study. 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1. Schematic CONSORT (Consolidated Standards of Reporting Trials) flowchart for the 
study 
 
The therapist will determine baseline characteristics for every participant through a standardized 
assessment form. During the baseline measurement, the following characteristics will be recorded: 
sex, age, body mass, pain characteristic, history of disease and medication use. The participant's 
participation schedule will be determined according to the SPIRIT (Standard Protocol Items: 
Recommendations for Interventional Trials) statement Figure 2. The primary and secondary 
outcome measures will be recorded before providing the intervention. 
 
 
 
 
STUDY PERIOD 
 
Enrolment 
Allocation 
Post-allocation 
Close-out 
TIMEPOINT** 
 
0 
1st 
week 
2nd 
week 
3rd 
week 
1st 
day 
1st 
week 
2nd 
week 
Post 3rd 
week 
ENROLMENT: 
 
 
 
 
 
 
 
 
 
Eligibility screen 
X 
 
 
 
 
 
 
 
 
Assess for eligibility (n=86) 
Randomized (n=72) 
Excluded (n=….) 
Not meeting inclusion criteria (n=….) 
Declined to participate (give reason) 
(n=….) 
Allocated to Curcuminoid capsules Group (n=36) 
Lost to follow up (give reason) (n=….) 
Discontinued intervention (give reason) (n=….) 
Analyzed (n=….) 
Excluded from analyzed (give reason) (n=….) 
Allocation 
Follow-up 
Analysis 
Allocated to Placebo Group (n=36) 
Lost to follow up (give reason) (n=….) 
Discontinued intervention (give reason) (n=….) 
 
Analyzed (n=….) 
Excluded from analyzed (give reason) (n=….) 
 

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Protocol No. KE_FK_0674_EC_2023 
Date: 06/10/2023 
Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins, and Quality of Life in Elderly People With Osteoarthritis Genu   
 
Informed consent  
X 
 
 
 
 
 
 
 
 
[Radiography and 
MMSE Test] 
X 
 
 
 
 
 
 
 
 
Allocation 
 
X 
 
 
 
 
 
 
 
INTERVENTIONS: 
 
 
 
 
 
 
 
 
 
[C Therapy] 
 
 
X 
X 
X 
 
 
 
 
[P Therapy] 
 
 
X 
X 
X 
 
 
 
 
ASSESSMENTS: 
 
 
 
 
 
 
 
 
 
[Demographic 
Details] 
X 
 
 
 
 
 
 
 
 
[TNF-Alpha] 
 
 
 
 
 
X 
 
 
X 
[Interleukin-1] 
 
 
 
 
 
X 
 
 
X 
[C-Reactive 
Protein] 
 
 
 
 
 
X 
 
 
X 
[Knee Pain] 
 
 
 
 
 
X 
X 
X 
X 
 
Figure 2. SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) recommended 
schedule for participation.

Page 11 
 
Protocol No. KE_FK_0674_EC_2023 
Date: 06/10/2023 
Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins, and Quality of Life in Elderly People With Osteoarthritis Genu   
 
 
 
6 
Intervention  
After the standardized assessments and baseline measurements, the intervention will be conducted. 
Participants will be randomly assigned to the C group or the P group. Each participant will be exposed 
to taking Curcuminoid capsules three times a day for 21 days. Participants will not be allowed to take 
any medication routinely during this time except for antihypertensive agents, thyroid medications, 
and antidiabetic drugs. To help participants adhere to the interventions, reminder messages will be 
sent before each session visit.  
 
The patient is observed for a local twitch response. The patient is asked to report any abnormal 
sensations or discomfort during intervention. 
 
The sponsor will provide double-blind study medication for Curcuminoid and Placebo 
Preparation of standardized curcuminoid turmeric extract. Samples were made from extracted 
turmeric and then optimized. The capsule formulation is made from turmeric rhizome extract which 
contains 30 mg of curcuminoids per capsule. In the study, standardized curcuminoid turmeric 
extract was given in capsules at 30 mg 3 times a day for 3 weeks.  
 
7 
Outcomes  
All outcome measures will be assessed at baseline and after 3 weeks of intervention. 
 
Primary Outcomes measures 
1) Secretion of the TNF-Alpha  
TNF alpha is a cytokine, a protein that plays a role in the immune system and inflammation. TNF 
alpha is produced by various types of cells, particularly activated macrophages, and plays a role in 
various biological processes such as inflammation and immunity against infection. 
The cytokine TNF alpha is an essential mediator in increasing the inflammatory response, which 
can be detected in the blood plasma of patients with Osteoarthritis. The TNF alpha examination was 
conducted using the Enzyme Linked Immunosorbent Assay (ELISA) method on blood plasma. 
2) Secretion of Interleukin-1 
Interleukin-1 is a pro-inflammatory cytokine that plays a key role in immune and inflammatory 
responses, produced primarily by macrophages. IL-1 can cause fever, increase blood vessel 
permeability, and trigger bone and cartilage damage.  
The cytokine Interleukin-1 is an essential mediator in increasing the inflammatory response, which 
can be detected in the blood plasma of patients with Osteoarthritis. The Interleukin-1 examination 
was conducted using the Enzyme Linked Immunosorbent Assay (ELISA) method on blood plasma 
3) Secretion of C-Reactive Protein 
C-reactive protein (CRP) is a blood marker for inflammation in the body, produced by the liver in 
response to infection, injury, or autoimmune conditions. A simple blood test measures CRP levels, 
with higher concentrations indicating greater inflammation.  
C-reactive protein (CRP) is measured with a blood test to detect and monitor inflammation in your 
body. A blood sample is taken from a vein and analyzed in a laboratory to determine the CRP level. 
The results are reported in milligrams per liter (mg/L), and higher than normal levels indicate 
inflammation that may be caused by infection, injury, or a chronic condition. 
 
 

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Protocol No. KE_FK_0674_EC_2023 
Date: 06/10/2023 
Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins, and Quality of Life in Elderly People With Osteoarthritis Genu   
 
Secondary outcomes 
The effectiveness of therapy is the ability of the therapy regimen given to suppress several other 
expected output indicators. Other output indicators were measured before starting therapy and after 
3 weeks of therapy is knee pain as measured by the VAS score 
 
8 
Statistical Issues 
Sample size 
The following formula estimates sample size 
N = 
2σ2(𝑍1−α/2 + 𝑍1−β)2
(µ1− µ2)2
 
where N is the sample size required in both groups, s is the standard deviation of the primary 
outcome. This research has a confidence level (1- 𝑎) of 95%, so the value obtained is 𝑎 = 5%. 
Therefore, the research hypothesis is unidirectional, so the magnitude of Z1-𝑎 = 1.96. The 
research's power (1-𝛽) was also set at 80%, so the value of 𝛽 = 20%, then the amount of Z1-𝛽 = 
0.842. Previous research analyzed changes in leukocytes in subjects treated with curcuminoid 
therapy from turmeric extract 30 mg 3 times a day for 14 days, amounting to 30.00 ± 5.10 and 
meloxicam 1 x 15 mg per day, obtained the mean delta value of leukocytes in the control group was 
164.1+50.91 and the treatment group was 174.27+78.93. 
 
N = 
2σ2(𝑍1−α/2 + 𝑍1−β)2
(µ1− µ2)2
 
    = 
2(14,01)2(1,96+0,842)2
(174,27−164,1)2
 
N = 
392,5602 (2,802)2
(174,27−164,1)2  
N = 
3082,07
103,4289 
N = 29,79 – (30 people) 
 
The total respondents required in the 2 groups is 60 people. Considering a dropout rate of 20%, the 
sample size should be increased to 36 each group. 
 
9 
Protection of Human Subjects and Assessment of Safety  
9.1 Protection of participants 
The ethics research committee has approved the study protocol registered with the Forum for 
Ethical Review Committees in Asia and the Western Pacific (FERCAP) (project number KE-FK-
0674-EC-2023). The study will be conducted according to Indonesia's 2021 National Health 
Research and Development Ethical Guidelines and Standards by the Health Research and 
Development Ethics Committee and the Helsinki Declaration, revised in 2013. 
 
9.2 Adverse events 
We will look for any adverse events that might occur during each administration of CA Therapy, 
including increased soreness, pain, numbness, and tingling. Any adverse event that is life-
threatening or related to significant disability will be reported to the ethics research committee of 
the institution. 
 
9.3 Data analysis 

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Protocol No. KE_FK_0674_EC_2023 
Date: 06/10/2023 
Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins, and Quality of Life in Elderly People With Osteoarthritis Genu   
 
The secondary researcher will analyze the data collected. Descriptive statistics will be used to 
evaluate the baseline characteristics of participants. The normality of the collected data will be 
established using the Shapiro–Wilk test. Based on data normality, descriptive statistics will be 
expressed as mean ± standard deviation or median (interquartile range). Within-group comparisons 
will be conducted using the Wilcoxon signed-rank test or a paired t-test. Similarly, the Mann–
Whitney U test or an independent t-test will be used for between-group comparisons. The level of 
significance will be set at 0.05. 
 
9.4 Data management 
Data collected will be kept confidential throughout the study and discarded after 5 years. Initial data 
documentation will be performed through printed data-collection forms, which will later be 
managed and transcribed into electronic format and stored on a desktop computer without an 
internet connection (to help prevent unauthorized data access) for further analysis. The chair of the 
student project committee of the institute will oversee data 
 
10. Ethical considerations 
10.1 Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported by the ICH 
Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local regulations 
(including Indonesia's 2021 National Health Research and Development Ethical Guidelines and 
Standards by the Health Research and Development Ethics Committee and with the ethical 
principles laid down in the Declaration of Helsinki. 
 
10.2 Informed consent procedures 
Eligible patients may only be included in the pre-screening or the study after providing written 
(witnessed, where required by law or regulation), IRB/IEC-approved informed consent, or, if 
incapable of doing so, after such consent has been provided by a legally acceptable 
representative(s) of the patient. In cases where the patient's representative gives consent, the 
patient must be informed about the pre-screening and the study, as applicable, to the extent 
possible given his/her understanding. If the patient can do so, he/she must indicate assent by 
signing and dating the written informed consent document or a separate assent form. Informed 
consent must be obtained before conducting any pre-screening or study- specific procedures (e.g. 
pre-screening assessments/all of the procedures described in the protocol). The patient source 
documents must document the process of obtaining informed consent. 
Novartis will provide to investigators in separate documents proposed pre-screening and study 
informed consent forms that comply with the ICH GCP guideline and regulatory requirements 
and are considered appropriate for pre-screening and participation in the study. Novartis must 
agree to any changes to the proposed consent forms suggested by the investigator before 
submission to the IRB/IEC, and a copy of the approved version must be provided to the Novartis 
monitor after IRB/IEC approval. 
Women of childbearing potential must be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that to 
participate in the study they must adhere to the contraception requirement for the duration of the 
study. If there is any question that the patient will not reliably comply, they must not be entered 
in the study. 
 
10.3 Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion from the 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, informed 
consent form(s), consent form updates, patient recruitment procedures (e.g., advertisements) and any 

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Protocol No. KE_FK_0674_EC_2023 
Date: 06/10/2023 
Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins, and Quality of Life in Elderly People With Osteoarthritis Genu   
 
other written information to be provided to patients. Prior to study start, the investigator is required 
to sign a protocol signature page confirming his/her agreement to conduct the study by these 
documents and all of the instructions and procedures found in this protocol and to give access to all 
relevant data and records to monitors, auditors, Quality Assurance representatives, designated agents 
of IRBs/IECs, and regulatory authorities as required. If a regulatory authority requests an inspection 
of the clinical site, the investigator must inform IRBs/IECs immediately that this request has been 
made. 
 
10.4 Publication of study protocol and results 
The critical design elements of this protocol will be posted in a publicly accessible database 
such as clinicaltrials.gov. In addition, upon study completion and finalization of the study report, 
the trial results will be either submitted for publication and posted in a publicly accessible 
database of clinical trial results. 
 
11. Protocol adherence 
This protocol defines the study objectives, procedures, and data to be collected on study 
participants. Additional assessments required to ensure safety of patients should be administered 
as deemed necessary on a case by case basis. Under no circumstances is an investigator allowed 
to collect additional data or conduct any additional procedures for any research-related purpose 
involving any investigational drugs under the protocol. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by the 
IRB/IEC and health authorities, where required, it cannot be implemented. 
 
 
11.1 Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by health authorities where required, and the IRB/IEC prior to 
implementation. Only amendments intended to eliminate an apparent immediate hazard to 
patients may be implemented immediately provided the health authorities are subsequently 
notified by protocol amendment and the reviewing IRB/IEC is notified. Notwithstanding the 
need for approval of formal protocol amendments, the investigator is expected to take any 
immediate action required for the safety of any patient included in this study, even if this action 
represents a deviation from the protocol.. 
 
 
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