Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on Inflammatory Markers, Endorphins and Quality of Life in Elderly People With Osteoarthritis Genu
Phase: PHASE1
Conditions: Osteoarthritis, Knee
Sponsor: Gadjah Mada University

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   
Page 1 
 
 
Cover 
 
 
Effect of a Combination of Curcuminoid Standardized Turmeric 
Extract with Acupressure on Inflammatory Markers, Endorphins 
and Quality of Life Elderly with Osteoarthritis Genu 
 
 
 
 
  
 
 
 
 
 
 
 
Investigator 
Srinalesti Mahanani 
Nyoman Kertia 
Ema Madyaningrum 
 
 
 
 
 
 
FACULTY OF MEDICINE GADJAH MADA UNIVERSITY 
INDONESIA 
 
 

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   
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 .................................................................................................................................. 8 
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 ................................................................................................................................. 12 
Primary Outcomes measures ................................................................................................... 12 
Secondary outcomes ................................................................................................................ 12 
8 
Statistical Issues ....................................................................................................................... 13 
Sample size .............................................................................................................................. 13 
9 
Protection of Human Subjects and Assessment of Safety ....................................................... 14 
9.1 Protection of participants ................................................................................................... 14 
9.2 Adverse events ................................................................................................................... 14 
9.3 Data analysis ...................................................................................................................... 14 
9.4 Data management .............................................................................................................. 14 
10. Ethical considerations .............................................................................................................. 15 
10.1 
Regulatory and ethical compliance .............................................................................. 15 
10.2 
Informed consent procedures ....................................................................................... 15 
10.3 
Responsibilities of the investigator and IRB/IEC ........................................................ 15 

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   
Page 3 
 
10.4 
Publication of study protocol and results ..................................................................... 15 
11. Protocol adherence .................................................................................................................. 16 
11.1 
Protocol amendments................................................................................................... 16 
12. References ............................................................................................................................... 16 

Page 4 
 
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   
 
 
 
 
 
Protocol summary 
Unique Protocol ID 
KE/FK/0674/EC/2023 
Title 
Effect of a Combination of Curcuminoid Standardized Turmeric Extract 
with Acupressure on Inflammatory Markers, Endorphins and Quality of 
Life Elderly with Osteoarthritis Genu 
Brief title 
Combination of Curcuminoid With Acupressure for Inflammationand Pain 
in the Elderly With Osteoarthritis Genu 
Sponsor and Clinical 
Phase 
Gadjah Mada University, Phase 2a 
Investigation type 
Drug and acupressure 
Study type 
Interventional 
Purpose and rationale 
Evaluate the efficacy, safety and tolerability of acupressure and 
standardized curcuminoid from turmeric extract to inflammatory markers, 
endorphin hormones in the blood and quality of life in elderly patient with 
Osteoarthritis Genu 
Primary Objective(s) 
To 
determine 
the 
effectiveness 
of 
combination 
two 
regimens 
(acupressure and curcuminoid) as measured by changes from baseline 
(BL) in Leukocytes, Neutrophil Leukocyte Ratio, Blood Sedimentation 
Rate, Pain, secretion of COX-2 and Endorphin hormones in blood to 
placebo after 3 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 3 weeks : 
 
Knee pain as measured by the VAS score  
 
Joint stiffness and joint functional ability are assessed by the 
WOMAC score  
 
The independence of the elderly as assessed by the Barthel Index  
 
Quality of Life were measured by Respondents' satisfaction in 
carrying out daily activities based on indicators on the KOOS 
instrument 
Study design 
Randomized controlled trial, double-blind to assess efficacy, tolerability 
and safety combination of acupressure and curcuminoid versus placebo. 
Patients can be pre-screened for certain x-ray and laboratory 
parameters. Following a screening visit, eligible subjects will enter the 
wash-out for 1 week. After the wash-out period, eligible subjects will be 
randomized and treated for 3 weeks. The total duration of the study is up 
to 5 weeks 
Population 
Approximately 70 female and male patients ≥ 65 years old 
Key Inclusion criteria 
 
Clinical diagnosis of osteoarthritis which 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 

Page 5 
 
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   
 
 
 
Key Exclusion criteria  
Parkinson's disease  
 
Dementia disease 
 
Psychosis  disease 
 
New bone fractures 
 
Joint dislocations 
 
Cancer 
 
Rrheumatic 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  
Leukocytes 
 
Neutrophil Leukocyte Ratio 
 
Blood Sedimentation Rate 
 
Pain 
 
Secretion of COX-2 in blood 
 
Secretion of Endorphin hormones in blood 
Key safety assessment  
Physical examination 
 
Vital signs 
 
Monitoring of laboratory markers in blood 
Others assessment 
 
Quality of Life 
Data analysis 
The primary efficacy variable is the number of Leukocytes (mcL), 
Neutrophil Leukocyte Ratio, Secretion of COX-2 in blood, Secretion of 
Endorphin hormones 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 wilcoxon signed-rank test or paired t test and 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 2 weeks of 
intervention 
Keywords 
Osteoarthritis, curcuminoid, acupressure, randomized control trial 

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 a decrease in joint fluid volume which is 
exacerbated by bearing the weight of the body. 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 quality of life in Osteoarthritis. Popular alternative 
therapies include herbal therapy, therapeutic touch, relaxation techniques, music therapy, 
acupuncture, and acupressure. One of the therapies that is very close to the community, 
especially the Javanese, is acupressure, which is 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 the use of non-
steroidal anti-inflammatory drugs (NSAIDs), but these drugs carry the risk of 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. This alternative therapy, unlike the use of drugs, 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 and 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 Osteoathritis 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) and 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 with a 
duration of 30 minutes each time. The results showed that the average pain score in the 
intervention group decreased significantly from 5.89 at the beginning of the study 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 adjusting for age, weight, and pretreatment 
covariates. 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 

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   
 
control). This study revealed that respondents who received acupressure therapy for 3-4 weeks 
with the duration of each therapy being 10-15 minutes, showed a significant reduction in the 
total WOMAC index, pain and physical dysfunction. 
So far, there has been no research 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 acupressure and standardized curcuminoids from turmeric 
extract to inflammatory markers, endorphin hormones in the blood and quality of life 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 Leukocytes, Neutrophil Leukocyte Ratio, Blood 
Sedimentation Rate, Pain, secretion of COX-2 and Endorphin hormones 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 Quality of Life that were measured by Respondents' satisfaction in 
carrying out daily activities based on indicators on the Knee injury and Osteoartritis Outcome 
Score (KOOS) instrument 
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 combination of acupressure 
and curcuminoid versus placebo. 
 
Pre-Screening:   
Patients can be pre-screened for certain x-ray and laboratory parameters. Following a 
screening visit, eligible subjects will enter the wash-out. After the wash-out 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. 
 
 
 
 
 

Page 8 
 
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   
 
Participants will be recruited from Agustus 2023 to September 2023. 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 (g65 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 70 patients. Since a 25% screening failure rate and a 20% washout failure rate 
is expected, 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 any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients. 
1. Parkinson's disease  
2. Dementia disease 
3. Psychosis  disease 
4. New bone fractures 
5. Joint dislocations 
6. Cancer 
7. Rrheumatic 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 

Page 9 
 
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   
 
3) Grade 2: Minimal, few osteophytes on the tibia and patella and the joint surface is 
asymmetrically narrowed. 
4) Grade 3: Moderate, there are moderate osteophytes 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. 
Mini Mental State Examination (MMSE) test will be used to assess the patient's cognitive abilities. 
This is important to ensure that patients can understand the instructions in the treatment process and 
the outcome measurement process.  
5 
Randomization, allocation and blinding 
A total of 70 eligible participants will be randomized to the group with curcuminoids capsules and 
acupressure (C+A; group 1) or the group with placebo and sham acupressure (P+S; group 2) via 
lottery randomization. Thereafter subjects will be randomly allocated to C+A and P+S 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 
 
Determination of baseline characteristics for every participant will be done by the therapist 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. 
Assess for eligibility (n=86) 
Randomized (n=72) 
Excluded (n=….) 
Not meeting inclusion criteria (n=….) 
Declined to particate (give reason) (n=….) 
Allocated to Curcuminoid capsules and 
Acupressure 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 and Sham Acupressure 
Group (n=36) 
Lost to follow up (give reason) (n=….) 
Discontinued intervention (give reason) (n=….) 
 
Analyzed (n=….) 
Excluded from analyzed (give reason) (n=….) 
 

Page 10 
 
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   
 
 
 
 
 
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 
 
 
 
 
 
 
 
 
Informed consent  
X 
 
 
 
 
 
 
 
 
[Radiography and 
MMSE Test] 
X 
 
 
 
 
 
 
 
 
Allocation 
 
X 
 
 
 
 
 
 
 
INTERVENTIONS: 
 
 
 
 
 
 
 
 
 
[C+A Therapy] 
 
 
X 
X 
X 
 
 
 
 
[P+S Therapy] 
 
 
X 
X 
X 
 
 
 
 
ASSESSMENTS: 
 
 
 
 
 
 
 
 
 
[Demographic 
Details] 
X 
 
 
 
 
 
 
 
 
[Inflammatory 
Marker] 
 
 
 
 
 
X 
 
 
X 
[Endorphine] 
 
 
 
 
 
X 
 
 
X 
[Quality of Life] 
 
 
 
 
 
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 CA group or the PS group. For Acupressure Therapy 
and Sham Acupressure, each participant will be exposed to 3 therapy sessions per week of 20 
minutes for 3 consecutive weeks. 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. For Curcuminoid capsules and placebo, Each participant will be exposed to taking capsules 
three times a day for 21 days. 
Acupressure to perform CA, the patient is put in the supine position with legs straight. Prepare tools 
and materials such as a seat (or bed), warm water, olive oil, wet & dry tissue, towels. The therapist 
washes his hands, the client sits in a comfortable position. Teach patients breathing relaxation 
techniques to use during therapy. Give patients the opportunity to pray according to their respective 
beliefs. Make sure the client is relaxed and comfortable. Help remove the client's clothing or 
accessories that may hinder the acupressure action being performed, if necessary. Perform a client 
pain assessment. Wipe the client on the parts to be massaged with warm water that has been treated 
with a disinfectant solution using a small towel. Dry with a clean towel. Use cream or oil, do a 
warming massage with basic massage techniques, choose according to the client's condition 
(rubbing, squeezing, pressing) and stretching the patient's feet. Acupressure massage points are 
performed at ST34, ST36, Tai Xi Acupoint, GB34, SP 9, SP 8, EX-LE, EX-LE3, EX-LE4, EX-
LE6, EX-LE7, EX-LE10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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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 patient is observed for a local twitch response. The patient is asked to report any abnormal 
sensations or discomfort during the course of intervention. 
 
The sponsor will provide double-blind study medication for Curcuminoid and Plasebo 
Preparation of standardized curcuminoid turmeric extract preparations. 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 a concentration of 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) Inflammatory Markers 
Inflammation markers are carried out by measuring leukocyte numbers and the Neutrophil 
Lymphocyte Ratio. The examination is carried out using a complete blood test using a Hematology 
Analyzer, which is a laboratory tool used to measure and count the number of blood cells. The 
blood samples are mixed using a mixture of reagents to create a process called hemolyzing. This 
process will be divided into several purposes, to measure leukocytes, neutrophils, platelets and 
erythrocytes. 
2) Secretion of the COX-2 hormone 
The enzyme cycloxygenase-2 (COX-2) is an important mediator in increasing the inflammatory 
response. In the blood plasma of patients with osteoarthritis, the COX-2 enzyme can be detected. 
The COX-2 hormone examination was carried out using the Enzyme Linked Immunosorbent Assay 
(ELISA) method on blood plasma. 
3) Secretion of endorphin hormones 
Endorphins, in this case beta endorphin, are hormones released by the pituitary gland in response to 
stress or pain, which are also secreted in blood plasma. Endorphin hormone levels in the blood were 
measured before starting therapy and after 3 weeks of therapy. 
Endorphin hormone examination is carried out using the Enzyme Linked Immunosorbent Assay 
(ELISA) method on blood plasma that has been incubated at room temperature for 10-20 minutes, 
then the tube will be centrifuged for 20 minutes at a speed of 2000-3000 rpm. 
 
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 
1) Knee pain as measured by the VAS score 
2) Joint stiffness and joint functional ability are assessed by the WOMAC score. 
WOMAC is a questionnaire developed by Bellamy (Bellamy et al., 1988) and continues to be 
developed to measure the functional abilities of patients with knee osteoarthritis. The WOMAC 
instrument has been translated into Indonesian and has been tested for validity by Karsten (Karsten 
et al., 2019) with the results of the Crohnbach's Alpha coefficient of 0.966, indicating that there is 
relatively high internal consistency and is highly correlated, meaning that the WOMAC 
questionnaire in Indonesian is correct. validated and can be used by the Indonesian people. This 
questionnaire can evaluate 3 subscales, namely (1) pain (5 items), (2) stiffness (2 items) and (3) 

Page 13 
 
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   
 
physical function (17 items) by scoring on a 5-point ordinal scale. The details of the scores are (1) 
pain: score 0 "no pain", score 1 "mild pain", score 2 "moderate pain" score 3 "severe pain" and 
score 4 "very severe pain"; (2) stiff: score 0 "not stiff", score 1 "mildly stiff", score 2 "medium 
stiff", score 3 "extremely stiff" and score 4 "stiff to the point of locking"; (3) physical function: 
score 0 "not difficult", score 1 "somewhat difficult", score 2 "quite difficult", score 3 "very 
difficult" and score 4 "very difficult". Range of subscale scores for pain (0-20), stiffness (0-8) and 
physical function (0-68). The total score is obtained by adding up the scores of the 3 subscales, with 
a maximum score of 96. A higher WOMAC score indicates pain, stiffness and worse physical 
function. The total WOMAC score can be categorized into 3 groups, namely low risk (score f 60), 
moderate risk (score 60-80) and high risk (score g 81). 
 
3) The independence of the elderly as assessed by the Barthel Index 
The Barthel Index questionnaire was first developed in 1965 by Mahoney. Inventory of this 
instrument is held by The Maryland State Medical Society. Then in 2020, Pontansi (Pontung & et 
al, 2020) translated it into Indonesian and carried out a validity test with the result that inter-rater 
reliability was satisfactory. 
In terms of content validity, the Indonesian version of the Barthel Index is acceptable. The construct 
validity test revealed two main factors, namely functional performance and physiological function. 
 
4) Quality of Life assessed with KOOS 
KOOS is an instrument to assess patient opinions about the condition of the knee and problems 
related to the knee. KOOS has been translated into Indonesian and tested for validity by Phatama 
(Phatama & et al, 2021) with Cronbach α results of 0.84 to 0.97 for all subscales, indicating 
adequate internal consistency. Test-retest reliability was excellent, with intraclass correlation 
coefficients ranging from 0.91 to 0.99 for all subscales. No significant differences were found in 
KOOS subscale responses between the first administration of the questionnaire and the second 
administration within 21 days. The Indonesian version of the KOOS was declared valid and reliable 
and therefore is an objective instrument for evaluating knee ligament injuries and knee 
osteoarthritis in the Indonesian population. KOOS can be used as a measurement of quality of life 
because it includes measurements of 5 subscales, namely (1) Symptoms; (2) Rigidity; (3) Pain; (4) 
Daily Activities; (4) Sports and Recreation Activities and (5) Knee-related Quality of Life. in 
circumstances one week prior is the time period considered when answering the question. Answer 
options are standard (Likert scale) and each question is scored from 0 to 4. Scores are normalized (a 
score of 100 indicates no symptoms and 0 indicates extreme symptoms). 
 
8 
Statistical Issues 
Sample size 
Sample size is estimated by the following formula 
N = 
                   
         
 
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- �㕎) of 95%, so the value obtained is �㕎 = 5%. 
Therefore, the research hypothesis is unidirectional, so the magnitude of Z1-�㕎 = 1.96. Power (1-�㗽) 
in the research was also set at 80%, so that the value of �㗽 = 20% then the amount of Z1-�㗽 = 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. 
 

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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   
 
N = 
                   
         
 
    = 
                      
               
 
N = 
                 
                
N = 
       
         
N = 29,79 – (30 orang) 
 
This gives the total number required in the 2 groups. 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 study protocol has been approved by the ethics research committee 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 the presence of any adverse events that might occur during each administration of 
CA Therapy, which include 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 
The data collected will be analyzed by the secondary researcher. 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-groups comparisons. The level of 
significance will be set at 0.05. 
 
9.4 Data management 
Data collected will be kept confidential throughout the study duration and will be discarded after 5 
years. Initial documentation of data 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. Data 
will be overseen by the chair of the student project committee of the institute 
 
 
 
 
 
 
 

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Inflammatory Markers, Endorphins and Quality of Life in Elderly People With Osteoarthritis Genu   
 
10. Ethical considerations 
10.1 Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in accordance 
with 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 in 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/or the study, as applicable, to the extent 
possible given his/her understanding. If the patient is capable of doing so, he/she must indicate 
assent by personally 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 process of obtaining informed consent must be documented in the patient source 
documents. 
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 for participation in the study. Any changes 
to the proposed consent forms suggested by the investigator must be agreed to by Novartis 
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 child bearing 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 in order 
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 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 in accordance with 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 an inspection of the clinical site is requested by a regulatory authority, the investigator 
must inform IRBs/IECs immediately that this request has been made. 
 
10.4 Publication of study protocol and results 
The key 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 
results of this trial will be either submitted for publication and/or posted in a publicly accessible 
database of clinical trial results. 
 

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Inflammatory Markers, Endorphins and Quality of Life in Elderly People With Osteoarthritis Genu   
 
11. Protocol adherence 
This protocol defines the study objectives, the study procedures and the 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 that are 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.. 
 
 
12. References 
 
Adamczak, A., Ożarowski, M., & Karpiński, T. M. (2020). Curcumin, a Natural Antimicrobial 
Agent with Strain-Specific Activity. Pharmaceuticals (Basel, Switzerland), 13(7). 
https://doi.org/10.3390/ph13070153 
Akbarnezhad, N., Shahboulaghi, F. M., Khankeh, H., Sokhangouie, Y., Biglarian, A., & Modanloo, 
S. (2019). The effect of acupressure therapy on pain, stiffness and physical functioning of 
knees among older adults diagnosed with osteoarthritis: A pilot randomized control trial. 
European Journal of Integrative Medicine, 28, 68–75. 
https://doi.org/10.1016/j.eujim.2019.04.007 
Alinaghizadeh, M, Hawkins, J., Abbassian, A., Seif barghi, T., Ayati, M. H., & Alizadeh vaghasloo, 
M. (2021). Effect of Persian acupressure (Ghamz) on Patients with Knee Osteoarthritis: A 
Single-Blinded Parallel Clinical Trial. Pain Management Nursing, 22(6), 820–827. 
https://doi.org/10.1016/j.pmn.2021.06.002 
Alinaghizadeh, Maryam, Hawkins, J., Abbassian, A., Seif Barghi, T., Ayati, M. H., & Alizadeh 
Vaghasloo, M. (2021). Effect of Persian acupressure (Ghamz) on patients with knee 
osteoarthritis: A single-blinded parallel clinical trial. Pain Manag. Nurs., 22(6), 820–827. 
https://doi.org/10.1016/j.pmn.2021.06.002 
Bellamy, N., Buchanan, W., Goldsmith, C., & Al, E. (1988). Validation study of WOMAC: A 
health status instrument for measuring clinically important patient relevant outcomes to 
antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatology, 
15(12), 1833–1840. 
Bertorio, M. J. (2017). Efektivitas Kombinasi Ekstrak Temulawak, Jahe, Kedelai Dan Kulit Udang 
Dibandingkan Dengan Meloksikam Pada Pasien Osteoartritis Lutut. Universitas Gadjah 

Page 17 
 
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   
 
Mada. 
Chatawatee, B., Chokpaisarn, J., Yusuf, M., Waehama, F., Kunworarath, N., Kongsuwan, C., & 
Salaemae, M. (2022). Effectiveness of knee acupressure along with herbal knee poultice for 
knee osteoarthritis treatment: A pilot pre-post clinical study. Journal of Herbal Medicine, 32. 
https://doi.org/10.1016/j.hermed.2021.100498 
Cheung, D. S. T., Yeung, W.-F., Suen, L. K.-P., Chong, T. C., Ho, Y.-S., Yu, B. Y.-M., Chan, L. 
Y.-T., Chen, H.-Y., & Lao, L.-X. (2019). Self-administered acupressure for knee osteoarthritis 
in middle-aged and older adults: a pilot randomized controlled trial. Acupuncture in Medicine, 
38(2), 75–85. https://doi.org/10.1177/0964528419883269 
Croke, L. M. (2014). Treatment of knee osteoarthritis: a clinical practice guideline from the AAOS. 
American Family Physician, 89(11), 918–920. 
Dewi, S. (2014). Diagnosis dan Penatalaksanaan Osteoartritis. Perhimpunan Reumatologi 
Indonesia. 
Felson, D. . (2008). HARRISON’s Principles of Internal Medicine (Seventeent). McGraw-Hill 
Companies Inc. 
Guo, D., Ma, S., Zhao, Y., Dong, J., Guo, B., & Li, X. (2022). Self-administered acupressure and 
exercise for patients with osteoarthritis: A randomized controlled trial. Clinical Rehabilitation, 
36(3), 350–358. https://doi.org/10.1177/02692155211049155 
Hall, M., Migay, A. M., & Persad, T. (2008). Individuals’ experience of living with osteoarthritis of 
the knee and perceptions of total knee arthroplasty. Physiotherapy Theory and Practice, 24(3), 
167–181. https://doi.org/10.1080/09593980701588326 
Ho, K. K.-W., Kwok, A. W.-L., Wai-Wang, C., Xia, S. M., Wang, Y. L., & Cheng, J. C.-Y. (2021). 
A randomized controlled trial on the effect of focal thermal therapy at acupressure points 
treating osteoarthritis of the knee. Journal of Orthopaedic Surgery and Research, 16, 1–11. 
https://doi.org/http://dx.doi.org/10.1186/s13018-021-02398-2 
Horng, H.-C., Kuo, C.-P., Cherng, C.-H., Yeh, C.-C., Wang, T.-C., Liaw, W.-J., Ko, S.-C., & 
Wong, C.-S. (2013). The effects of collateral meridian therapy for knee osteoarthritis pain 
management: A pilot study. Journal of Manipulative and Physiological Therapeutics, 36(1), 
51–56. https://doi.org/10.1016/j.jmpt.2012.12.003 
Jang, M., Lim, Y.-M., & Park, H. (2019). Effects of auricular acupressure on joint pain, range of 
motion, and sleep in the elderly with knee osteoarthritis . Journal of Korean Academy of 
Community Health Nursing, 30(1), 79–89. https://doi.org/10.12799/jkachn.2019.30.1.79 
Jevsevar, D. S. (2013). Treatment of osteoarthritis of the knee: evidence-based guideline. JAAOS-
Journal of the American Academy of Orthopaedic Surgeons, 21(9), 571–576. 
Karsten, S., & et al. (2019). Translation, adaptation, and validation of western ontario and mcmaster 
universities osteoarthritis index (WOMAC) for indonesian. The Journal of Indonesian 
Orthopaedic & Traumatology, 2(3), 17–26. 
https://doi.org/https://doi.org/10.31282/joti.v2n3.48 
Karsten, S., Limena, S., & Phandu, M. (2019). Translation, adaptation, and validation of western 
ontario and mcmaster universities osteoarthritis index (WOMAC) for indonesian. Jurnal 
Orthopaedi Dan Traumatologi Indonesia (The Journal of Indonesian Orthopaedic & 
Traumatology), 2(3). https://doi.org/10.31282/joti.v2n3.48 
Kendall, J. M. (2003). Designing a research project: randomised controlled trials and their 

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Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins and Quality of Life in Elderly People With Osteoarthritis Genu   
 
principles. Emergency Medicine Journal, 20(2), 164–168. 
https://doi.org/10.1136/emj.20.2.164 
Kertia, N. (2009). Aktivitas Anti-Inflamasi Kurkuminoid Ekstrak Rimpang Kunyit (Curcuma 
domestica Val.) Kajian Klinis dan Laboratoris Pengaruhnya terhadap Respon Inflamasi di 
dalam Cairan Sinovia Sendi Osteoartritis. Universitas Gadjah Mada. 
Kertia, N., Asdie, A. H., & Rochmah, W. (2012). Comparison of the effects of curcuminoid from 
Curcuma domestica Val. rhizome extract and diclofenac sodium on the liver function of 
patients with osteoarthritis. Journal of Pharmacognosy and Phytotherapy, 4(5), 62–65. 
Kolcaba, K. Y. (1994). A theory of holistic comfort for nursing. Journal of Advanced Nursing, 
19(6), 1178–1184. https://doi.org/10.1111/j.1365-2648.1994.tb01202.x 
Leong, M., Smith, T. J., & Rowland-Seymour, A. (2015). Complementary and Integrative Medicine 
for Older Adults in Palliative Care. Clinical Geriatrics Medicine. 
https://doi.org/http://dx.doi.org/10.1016/j.cger.2015.01.004 
Li, L. W., Harris, R. E., Tsodikov, A., Struble, L., & Murphy, S. L. (2018). Self-Acupressure for 
Older Adults With Symptomatic Knee Osteoarthritis: A Randomized Controlled Trial. 
Arthritis Care & Research, 70(2), 221–229. https://doi.org/https://doi.org/10.1002/acr.23262 
Phatama, K., & et al. (2021). Knee Injury and Osteoarthritis Outcome Score: Validity and 
Reliability of an Indonesian Version. Ochsner Journal, 21, 63–67. 
https://doi.org/10.31486/toj.20.0088 
Pinsornsak, P., & Niempoog, S. (2012). The efficacy of Curcuma Longa L. extract as an adjuvant 
therapy in primary knee osteoarthritis: a randomized control trial. Journal of the Medical 
Association of Thailand = Chotmaihet Thangphaet, 95, S51-58. 
https://www.scopus.com/inward/record.uri?eid=2-s2.0-
84884547635&partnerID=40&md5=efc90d0c0b80318077a5d12f96164bb7 
Pongantung, H., & et al. (2020). Construct Validity Indonesian Version of Barthel Index for Post 
Stroke. Indian Journal of Public Health Research & Development, 11(3), 1996–2000. 
https://www.researchgate.net/publication/345705861%0AConstruct Validity 
Rani, M., Sharma, L., Advani, U., & Kumar, S. (2020). Acupressure as an Adjunct to 
Pharmacological Treatment for Depression, Anxiety, and  Stress in Patients with Knee 
Osteoarthritis. Journal of Acupuncture and Meridian Studies, 13(4), 129–135. 
https://doi.org/10.1016/j.jams.2020.07.001 
Rani, M., Sharma, L., Advani, U., & Sharma, A. (2021). Adjunctive effects of acupressure therapy 
on pain and quality of life in patients with knee osteoarthritis: an interventional study. Journal 
of Acupuncture and Tuina Science, 19(4), 300–306. https://doi.org/10.1007/s11726-021-1252-
x 
Sorour, A. S., Ayoub, A. S., & Abd El Aziz, E. M. (2014). Effectiveness of acupressure versus 
isometric exercise on pain, stiffness, and physical function in knee osteoarthritis female 
patients. Journal of Advanced Research, 5(2), 193–200. 
https://doi.org/10.1016/j.jare.2013.02.003 
Srivastava, S., Saksena, A. K., Khattri, S., Kumar, S., & Dagur, R. S. (2016). Curcuma longa 
extract reduces inflammatory and oxidative stress biomarkers in osteoarthritis of knee: a four-
month, double-blind, randomized, placebo-controlled trial. Inflammopharmacology, 24(6), 
377–388. https://doi.org/10.1007/s10787-016-0289-9 
Tomey, A. (2006). Nursing Theorist and Their Work (T. C. M. C. St. Louis (ed.); Sixth Edit). 

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Effect of Combination of Curcuminoid Standardized Turmeric Extract With Acupressure on 
Inflammatory Markers, Endorphins and Quality of Life in Elderly People With Osteoarthritis Genu   
 
Winangun. (2019). Diagnosis dan Tatalaksana Komprehensif Osteoartritis. Jurnal Kedokteran, 
5(1). https://doi.org/http://dx.doi.org/10.36679/kedokteran.v5i1.140 
 

This  research  aims  to  determine  the  effect  of  a  combination  of  turmeric  extract
mind  at  any  time  without  being  subject  to  any  fines  or  sanctions.
disease,  history  of  drug  use,  history  of  allergies,  smoking  habits.
which  exists.  This  interview  aims  to  measure  levels  of  anxiety  and  health
quality  of  life  of  elderly  with  genu  osteoarthritis.
treatment  at  Posyandu  Padukuhan  Tanjungsari,  Sukoharjo  Ngaglik  Sleman  Village
EXPLANATION  SHEET  TO  PROSPECTIVE  SUBJECTS
3.  Mr/Mrs/Sdr  will  undergo  a  physical  examination  by  a  doctor  to  check  the  status
Madyaningrum,  chaired  by  Srinalesti  Mahanani  from  the  Faculty's  Doctoral  Study  Program
This  research  requires  around  72  research  subjects,  with  a  period  of  participation
B.  Research  Procedures
This  consent  form  is  in  two  copies,  one  for  you  to  keep,  and  one  for  you
conducted  research  entitled  The  Effect  of  a  Combination  of  Standardized  Turmeric  Extracts
A.  Volunteering  to  participate  in  research
Elderly  with  Osteoarthritis  Genu.
If  you  have  decided  to  join,  you  are  also  free  to  withdraw/change
1.  Mr/Mrs/Br  will  be  interviewed  by  a  doctor  to  ask:  Name,  age,  history
We,  the  research  team  consisting  of  Srinalesti  Mahanani,  Nyoman  Kertia,  and  Ema
The  research  team  invites  fathers/mothers/relatives  to  take  part  in  this  research.
If  you  are  not  willing  to  participate  then  you  will  still  get
standardized  curcuminoids  with  acupressure  on  leukocyte  levels,  ESR,  NLR,  endorphins  and
2.  Mr/Mrs/Sdr  will  also  be  interviewed  with  several  questions  according  to  the  questionnaire
each  subject  approximately  4  weeks  -  2  months.
Medicine,  Public  Health  and  Nursing  Gadjah  Mada  University  will
If  you  are  willing  to  participate  in  this  research,  you  will  be  asked  to  sign
in  accordance  with  applicable  procedures.
your  mentality.
health
Curcuminoids  with  Acupressure  on  Inflammatory  Markers,  Endorphins  and  Quality  of  Life
You  are  free  to  choose  to  participate  in  this  research  without  any  coercion.  if  you
researcher.  The  next  procedure  is:
Machine Translated by Google

Blood  collection  is  carried  out  using  a  butterfly  needle  that  has  been  installed.
then  Mr/Ms/Sdr  will  be  divided  into  2  groups  randomly  so  that  there  are
research  (the  family  will  accompany  the  respondent  in  drinking  herbal  therapy,  filling
report  to  researchers  if  unbearable  pain  occurs  during  the  period
tablespoon,  and  the  next  intake  is  after  the  therapy  is  given
medicinal  ingredients.  Respondents  and  researchers  do  not  know  which  group  they  fall  into,  only
4.  Mr/Mrs/Br  will  undergo  an  X-ray  examination  of  the  knee
13.  Researchers  will  involve  posyandu  cadres  to  alert  patients  and  families
Stop  consuming  for  1  week
8.  This  first  blood  draw  is  for  laboratory  examination  regarding  the  condition
11.  On  the  appointed  day  and  for  the  next  21  days,  Mr/Mrs/Br  will  be  given
a  day.  And  also  Mr/Ms/Sdr  will  get  a  visit  schedule  for  therapy
9.  Blood  collection  is  carried  out  by  nurses  who  are  accustomed  to  taking  blood.
at  the  posyandu  at  6.45  for  further  blood  collection.
reminder  to  remind  the  family.
how  to  place  a  butterfly  needle  in  a  vein  in  the  forearm.
given  medication  and  therapy  as  well  as  groups  who  did  not  receive  medication  and  therapy
12.  This  research  will  involve  families  to  accompany  respondents  during  the  process
about  one  tablespoon
5.  If  you  use  painkillers,  you  will  be  asked  to
It  is  possible  that  the  capsule  given  to  you  may  not  contain  it
The  first  collection  is  carried  out  before  therapy  is  given  in  approximately  one  amount
observation  sheet  for  taking  medication  and  accompanying  when  administering  acupressure  therapy  as  well
blood  and  body  hormones.
6.  One  week  later  the  research  will  begin.  You  will  be  asked  to  come  together
The  medicine  is  in  capsule  form  which  must  be  taken  with  water  3  times
only  the  therapist  knows.
study).
taking  medication  and  doing  therapy,  as  well  as  researchers  will  create  a  system
7.  Blood  sampling  was  carried  out  twice  during  the  research  period
10.  Because  in  this  research  there  will  be  2  groups,  namely  the  group  that
acupressure.  Mr/Ms/Sdr  will  be  asked  to  come  to  the  therapist's  house  according  to  the  schedule.
Machine Translated by Google

straight  to  you.  During  the  research,  researchers  set  up  protective  measures
and  will  only  be  known  to  researchers,  research  staff  and  auditors.  The  research  results  will  be
H.  Financing
acupressure  according  to  that  received  by  the  treatment  group.
Turmeric  herbal  therapy  interventions  and  acupressure  massage  do  not  provide  any  side  effects
All  information  relating  to  the  identity  of  research  subjects  will  be  kept  confidential
As  research  subjects,  you  are  obliged  to  follow  the  rules  or  regulations
E.  Benefits
by  researchers  is  examination  by  a  doctor  and  treatment  in  hospital.
C.  Obligations  of  research  subjects
G.  Compensation
published  without  the  identity  of  the  research  subjects.
necessary  if  something  undesirable  happens.  Protection  provided
pharmacological  to  treat  pain  and  discomfort  due  to  Osteoarthritis  Genu  as  well
You  can  ask  the  researchers  further  questions.  During  the  research,  no
Mr/Ms/Sdr  will  get  tools  for  massage  therapy  (towel  and  oil).
All  costs  related  to  research  will  be  borne  by  the  researcher.
research  instructions  as  written  above.  If  something  is  not  clear,
The  direct  benefit  you  get  is  that  you  get  non-therapy
knee  joint  and  will  receive  therapy  in  accordance  with  the  provisions  of  the  study.
You  will  receive  an  X-ray  examination  to  determine  the  condition
F.  Confidentiality
D.  Risks  and  Side  Effects  and  Their  Management
Those  in  the  control  group  will  receive  herbal  therapy  and  therapy
the  next  will  be  yours.  After  the  research  activities  are  completed,  Mr./Ms./Br
permitted  to  take  other  medicines  or  herbal  medicines  other  than  those  given  by  the  researcher.
useful  for  further  treatment  at  home.
Machine Translated by Google

Mahanani  at  No.  Mobile  phone.  085729006547.
ext  17225  or  +62811-2666-869;  email:  mhrec_fmugm@ugm.ac.id).
If  you  need  further  explanation,  you  can  contact  Srinalesti
Medical  and  Health  Research,  Faculty  of  Medicine,  UGM  (Tel.  0274-588688,
in  connection  with  this  research.  If  at  any  time  side  effects  occur  or
You  can  also  ask  the  Ethics  Committee  about  research
You  are  given  the  opportunity  to  ask  anything  that  is  not  clear
I.  Additional  Information
Machine Translated by Google

CONSENT  TO  PARTICIPATE  IN  RESEARCH
By  signing  this  form,  I  agree  to  take  part  in  this  research
Witness  signature:
All  these  explanations  have  been  conveyed  to  me  and  all  my  questions  have  been  answered
Patient/subject  signature:
(Clear  name :.............................................. ..)
answered  by  the  researcher.  I  understand  that  if  I  need  an  explanation,  I  can
Date:
asked  Srinalesti  Mahanani.
(Clear  name :.............................................. ..)
Machine Translated by Google