Improving Sarcopenia During Chemotherapy
Phase: NA
Conditions: Early-stage Sarcopenia in Adult Cancer Patients Undergoing Chemotherapy
Sponsor: National Taiwan University Hospital

STUDY PROTOCOL  
 
official title: 
Improving Sarcopenia During Cancer 
Chemotherapy  
 
NCT Number: 
 
NTUH-REC No.: 202409133RIFE 
 
Jan 23, 2025 to Jan 22, 2026 
 
 
 
 
 
 
 
 
 
 
 
 
 

Research Purpose: 
In recent years, sarcopenia has become an important issue. According to statistical data from the 
literature, the prevalence of sarcopenia ranges from 3.9% to 7.3%, and it increases annually due to 
population aging. Elderly patients and cancer patients often suffer from multiple comorbidities, physical 
and cognitive impairments, and malnutrition. Elderly patients with cancer are more prone to significant 
muscle loss leading to sarcopenia during chemotherapy, which results in poor treatment tolerance, 
lower quality of life, increased mortality rates, decreased disease-free survival rates, and prolonged 
hospital stays (Pamoukdjian et al., 2017; Marhold et al., 2020; G. Colloca et al., 2018; NIPP et al., 
2017; Ryan et al., 2016).By collaborating with a multidisciplinary professional team, providing high-
protein nutritional interventions to cancer patients in the early stages of sarcopenia can help reduce 
muscle loss. This approach can mitigate the disability, cancer-related fatigue, and mortality caused by 
sarcopenia in cancer patients, and improve their quality of life. 
Project Summary: 
Background:With the rapid aging of the global population and the increasing number of cancer cases, 
the health issues of the elderly are gaining attention. According to the Ministry of the Interior, as of 
2020, individuals aged 65 and above constitute 16.1% of the total population, indicating a move 
towards a "super-aged society." Cancer is the leading cause of death in Taiwan, with the 2018 Cancer 
Registry Annual Report recording 116,131 new cancer cases. The physiological and functional decline 
associated with aging reduces daily activities, leading to malnutrition and disease-induced frailty, which 
in turn causes muscle atrophy, decreased muscle strength, slower walking speed, and balance problems, 
ultimately resulting in disability. This age-related disability imposes significant economic, medical, and 
caregiving burdens on society. Literature indicates that 5-13% of elderly cancer patients aged 60-70 and 
above suffer from sarcopenia. Exercise and nutrition are effective and highly autonomous interventions 
for improving sarcopenia.  
Objective: 
To evaluate the benefits of implementing a high-protein nutrition program during cancer chemotherapy 
and to explore the effectiveness of nutritional interventions in improving sarcopenia in cancer patients. 
Methods: 
Cancer patients aged 40 and above who meet the criteria for early-stage sarcopenia will receive an 8-
week high-protein nutritional intervention with the ETHANWELL BALANCED nutritional formula. 
Muscle strength and quality of life will be assessed. Paired sample tests will be used for statistical data 
analysis to investigate whether there are differences in the degree of sarcopenia among participants 
following the ETHANWELL BALANCED nutritional formula intervention。 
Inclusion and Exclusion Criteria: 
Inclusion Criteria: 
1. 
Age 40 and above. 
2. 
Patients receiving chemotherapy or expected to undergo thoracic surgery (stage I~IV) 
3. 
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and SARC-F score ≥ 4 
4. 
Grip strength: <28kg for males and <18kg for females. 
5. 
Conscious and able to communicate. 
Exclusion Criteria: 
1. 
Central nervous system disorders and chronic kidney failure. 

2. 
Mental illness or inability to cooperate. 
3. 
Expected survival period less than 3 months. 
4. 
Gastrointestinal dysfunction—patients who have undergone gastric resection surgery or have 
intestinal obstruction. 
5. 
Heart failure—NYHA class IV. 
6. 
Uncontrollable infection diagnosed by a physician. 
7. 
Poorly controlled diabetes diagnosed by a physician. 
8. 
End-stage renal disease—requiring hemodialysis or peritoneal dialysis. 
9. 
Liver cirrhosis with severe ascites. 
                                  
Research Method: 
A pre-post-test research design will be employed to investigate the effects of high-protein nutritional 
intervention on improving muscle strength, balance, nutrition, and quality of life in cancer patients with 
sarcopenia. Recruitment will be conducted in the thoracic ward or outpatient department of our hospital, 
with participants being allocated to either the experimental group or the control group. 
Recruitment will involve posting posters in the ward or outpatient department and researchers visiting 
these areas to recruit participants. Participants will be orally briefed about the trial and will provide 
informed consent by signing a consent form. Research assistants will then conduct grip strength tests 
using an electronic dynamometer, and only those with grip strength below 28kg for males and below 
18kg for females will be included in the trial. 
Participants will be randomly assigned to either the experimental group or the control group in a 2:1 
ratio, with 34 participants in the experimental group and 17 participants in the control group. The 
control group will receive 12 cans of ETHANWELL BALANCED nutritional formula free of charge 
upon completion of the study. Researchers will conduct pre-intervention assessments (grip strength test) 
and fill out the Fatigue Improvement and Quality of Life Scale, explaining the filling method and 
timing. 
Researchers will provide nutritional education and free high-quality protein nutritional products 
(ETHANWELL® BALANCED  nutritional formula), provided by Ethan Nutraceutical Co.,Ltd . Each 
serving of the ETHANWELL® BALANCED nutritional formula provides 250 kcal of energy, 13.5 
grams of protein (6.75 grams of whey protein and 2740 mg of BCAAs), and 166.953 mg of patented 
POLYCAN®  black yeast fermentation product (β-glucan 20.03 mg). It is consumed by mixing one 
serving with 220 ml of water below 40°C. Participants in the experimental group will consume 3 
servings of the ETHANWELL® BALANCED  nutritional formula per day, while the control group 
will receive standard treatment. The control group and maintained conventional treatment. And you 
need to perform five movements of elastic band training on your own, (Action 1. Lift up and press 
down, Movement 2. Straight arm lift, Movement 3. Seated rowing, Movement 4. Squat, Movement 5. 
Sitting leg raise, each movement is a group of 10 times) three groups each time, three times a week. 
Both groups of patients will sign consent forms and undergo assessments before intervention (pre-test), 
at 1 week (mid-test), 2 weeks (mid-test), 4 weeks (mid-test), 8 weeks (mid-test), and 12 weeks (post-
test) of nutritional intervention, including questionnaire completion and physiological measurements. 
Data collected will include mid-arm circumference, muscle strength, fatigue, quality of life, and blood 
test reports. 

The experimental group will receive at least one nutritional consultation via telephone from researchers 
each week. In addition to conventional treatment and high-protein nutrition intervention, the 
experimental group also required subjects to perform five movements of elastic band training on their 
own (movement 1: push up and press down, movement 2: straight arm lift, movement 3: seated rowing, 
movement 4: squat, movement 5: seated leg raise, each movement is 10 times in one group) three 
groups each time, three times a week. Subjects can refer to the elastic band exercise teaching。
https://youtu.be/ukO5bkiVXEU。 
Research has demonstrated that one way to increase muscle protein synthesis is to supplement with 
leucine in the diet. Leucine is one of the branched-chain amino acids (BCAAs), which include leucine, 
isoleucine, and valine. Among them, leucine can only be obtained from the diet in animals and cannot 
be synthesized endogenously. Its initial metabolism occurs in skeletal muscle rather than in the liver. 
BCAAs constitute approximately 35% of the essential amino acids in most mammals. [3]， The 
functional groups R of all three BCAAs are branched, small, and hydrophobic, making them key 
components of most proteins.[4]，Therefore, these three branched-chain amino acids are almost always 
ingested and metabolized together.[5]，There is abundant clinical evidence demonstrating that 
regulating protein turnover in skeletal muscle can be achieved by reducing protein degradation and 
increasing protein synthesis.[2]，Supplementing with BCAAs can increase the rate of intramuscular 
protein synthesis and improve protein synthesis in muscles.[1, 2, 6]。 
Beta-glucan is a dietary fiber composed of D-glucose monomers or polysaccharides, primarily linked 
by β-1,3/1,6-glucan connections, purified from Aureobasidium pullulans SM-2001 (EAP).[7, 8]， It 
also includes amino acids, monounsaturated fatty acids, or polyunsaturated fatty acids (such as linoleic 
acid and linolenic acid), and polysaccharides.[9]，The β-1,3/1,6-glucan is derived from the cell walls of 
natural bacteria, fungi, algae, and higher plants (such as grains).[7]。Beta-glucan can be enzymatically 
extracted from the cell walls of yeast, fungi, seaweed, or cereal seeds, and it can modulate various in 
vivo and in vitro activities. These specific components confer beta-glucan with anti-tumor, anti-
inflammatory, anti-obesity, anti-allergic properties, and immune-regulating activities. Research has 
found that EAP can improve muscle loss in elderly individuals and enhance muscle function.[8]。In 
animal experiments, it was found that EAP effectively inhibited dexamethasone-induced sarcopenia in 
mice.[10]；Another study indicated that EAP exhibited efficacy in exerting anti-osteoporotic effects in 
rats undergoing ovariectomy. [9] 
 
Assessment tools: 
conducted before and after the intervention include: 
1. 
Preoperative hand grip test (HGT) 
2. 
Brief Fatigue Inventory - Taiwanese version (BFI-T) 
3. 
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 
(EORTC) 
4. 
Blood tests: IL-6, CRP, TNF-α 
5. 
Mid-upper arm circumference measurement (MUAC) 
 
Sample Size 

The required sample size for this study was determined using statistical software Prism 6. To achieve 
statistical significance, Prism 6 software estimated that the experimental group would require 34 
participants, and the control group would require 17 participants, totaling 51 participants. The 
researchers also estimated that approximately 10% of participants might withdraw from the study 
prematurely. Therefore, the study aims to recruit 10% more participants than the required sample size. 
It is estimated that there will be 38 participants in the experimental group and 19 participants in the 
control group, totaling 57 participants meeting the criteria. 
Research flowchart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Post-intervention assessment (12 weeks after intervention): 
1.Grip strength test (conducted by the researcher) 
2.Fatigue improvement scale (administered by the researcher) 
3.Quality of life questionnaire (administered by the researcher) 
4.Mid-upper arm circumference measurement 
Post recruitment posters in the ward or 
register at outpatient clinics 
The researchers reviewed hospital records to 
screen for cases of cancer stages I to IV in 
individuals aged 40 and above, excluding those 
with a prognosis of less than three months of 
survival. 
The researchers explained the experimental protocol to the subjects and 
obtained their consent. Electronic grip strength tests were conducted, and only 
those who met the criteria were included in the study. Subsequently, the 
subjects were randomly assigned to either the experimental or control group. 
After determining their group, the subjects underwent pre-tests administered 
by the researchers: 
1. 
Preoperative grip strength test (researcher) 
2. 
Fatigue Improvement Scale (researcher) 
3. 
Quality of Life Questionnaire (researcher) 
4. 
Blood tests: IL-6, CRP, TNF-α, etc. 
Experimental group: 
1.Routine hospital/clinic care and 
nutritional education 
2.Provision of Ethanwell Balance 
high-protein nutritional powder 
Control group: 
Routine hospital/clinic care 
Mid-assessment (1, 2, 4, 8 weeks post-intervention): 
1.Grip strength test (by researcher) 
2.Fatigue Improvement Scale (by researcher) 
3.Quality of Life Questionnaire (by researcher) 
4.Blood tests: IL-6, CRP, TNF-α, etc. 
5.Mid-upper arm circumference measurement 
Researchers 
obtain the 
phone 
numbers 
from the 
participants' 
consent 
forms. They 
conduct 
weekly 
follow-up 
calls to track 
any issues 
with nutrition 
and the 
recording of 
dietary 
journals. 
They provide 
immediate 
guidance 
and 
counseling 
as needed. 
Researchers 
obtain 
participants' 
phone 
numbers 
from their 
consent 
forms. They 
conduct 
weekly 
follow-up 
calls to track 
participants' 
progress. If 
any 
questions 
arise, they 
refer the 
cases to the 
tumor case 
manager. 

 
Period 
Screening 
Treatment 
Baseline 
Follow-
up 
Visit 
V0 
V1 
V2 
V3 
V4 
V5 
Days 
- 14~0 
0 
14± 3 
28± 3 
56± 7 
84± 7 
Informed Consent Form Signed 
＊ 
 
 
 
 
 
Inclusion/Exclusion criteria evaluation 
＊ 
＊ 
 
 
 
 
Demographics 
＊ 
 
 
 
 
 
Medical/Surgical History 
＊ 
 
 
 
 
 
ECOG 
＊ 
 
 
 
 
 
SARC-F 
＊ 
 
 
 
 
 
hand-grip test5 
＊ 
＊ 
＊ 
＊ 
＊ 
＊ 
mid-upper arm circumference measurement6 
 
＊ 
＊ 
＊ 
＊ 
＊ 
Body weight1 
 
＊ 
＊ 
＊ 
＊ 
＊ 
Physical examination 
 
＊ 
＊ 
＊ 
＊ 
＊ 
Vital signs 
 
＊ 
＊ 
＊ 
＊ 
＊ 
Laboratory Tests 
 
 
 
 
 
 
 Albumin 
 
＊ 
 
＊ 
＊ 
＊ 
 Pre-albumin 
 
＊ 
 
＊ 
＊ 
＊ 
 BUN 
 
＊ 
 
＊ 
＊ 
＊ 
 Creatinin 
 
＊ 
 
＊ 
＊ 
＊ 
 Aspartate aminotranferase (AST) (GOT) 
 
＊ 
 
＊ 
＊ 
＊ 
 Alanine aminotransferase (ALT) (GPT) 
 
＊ 
 
＊ 
＊ 
＊ 
 Cholesterol 
 
＊ 
 
＊ 
＊ 
＊ 
 Triglyceride 
 
＊ 
 
＊ 
＊ 
＊ 
 Fasting Glucose 
 
＊ 
 
＊ 
＊ 
＊ 
 Ca, P, Mg2 
 
＊ 
 
＊ 
＊ 
 
 Uric Acid2 
 
＊ 
 
＊ 
＊ 
 
 IL-63 
 
＊ 
 
＊ 
＊ 
 
 CRP 
 
＊ 
 
＊ 
＊ 
 
TNF-α3 
 
＊ 
 
＊ 
＊ 
 
Randomization 
 
＊ 
 
 
 
 
   ETHANWELL BALANCED  
 
＊ 
＊ 
＊ 
＊ 
 
Diary Card4 
 
＊ 
＊ 
＊ 
＊ 
＊ 
BFI-T  
 
＊ 
＊ 
＊ 
＊ 
＊ 
EORTC 
 
＊ 
＊ 
＊ 
＊ 
＊ 
Concomitant Medication 
 
＊ 
＊ 
＊ 
＊ 
＊ 
Adverse Events 
 
＊ 
＊ 
＊ 
＊ 
＊ 
1. Body weight will be recorded by CRC using same platform scale.  
2 If abnormal value is found, the subject will be followed on next visit. 
3 IL-6/ TNF-αwill be examined for the interval of two months not otherwise the subject withdraw.  

4 Including nutritional supplement record.  
5 Hand-grip test will be recorded by CRC using same hand dynamometer. 
6. mid-upper arm circumference measurement will be recorded by CRC using same tape. 
 
Statistical analysis: 
Statistical analysis was performed using Prism 6 software for data processing and analysis. The basic 
demographics of the participants were presented using descriptive statistics. Considering the limited 
sample size, the Wilcoxon Signed-Rank Test was utilized to compare the assessment results before and 
after the intervention. All values were presented as mean ± standard deviation, and statistical 
significance was defined as p < 0.05. 
 
Literature review: 
According to the Population Statistics Report of 2020 in Taiwan, the population aged 65 and over 
accounted for 16.1% of the total population. It is projected to increase to 95.7% by 2060. The latest data 
from the Cancer Registry Annual Report in 2018 showed that there were 116,131 cases of cancer 
diagnosed in 2017, with an average age of 65 years. Cancer has been the leading cause of death in 
Taiwan for several years. Marzetti (2016) conducted a literature review suggesting that 30 minutes of 
resistance training combined with nutritional and vitamin D interventions for elderly individuals can 
reduce the risks of cardiovascular diseases, diabetes, stroke, depression, and falls. Loss of muscle mass 
due to cancer treatment leads to cancer-related sarcopenia, which makes it difficult for elderly cancer 
patients to tolerate treatment, resulting in poor prognosis, decreased quality of life, and reduced survival 
rates (Bozzetti, 2020; Davis et al., 2018). 
 
Sarcopenia, derived from the Greek roots "sarx" (flesh) and "penia" (deficiency), refers to the loss of 
muscle mass with aging (Colloca et al., 2019; Bozzetti, 2020). Zheng et al. (2016) defined sarcopenia as 
a complex syndrome caused by multiple pathogenic factors, including chronic diseases, hormonal 
changes, inflammation, insulin resistance, and malnutrition. Sarcopenia in older adults leads to physical 
function deterioration, impaired cardiorespiratory function, metabolic slowing, falls, disability, 
increased healthcare costs, and reduced quality of life (Davis et al., 2019; Stewart et al., 2019; Marhold 
et al., 2020). The comprehensive symptoms and disability caused by sarcopenia cannot be explained by 
a single disease or its pathology and require interdisciplinary collaboration to provide interventions to 
improve sarcopenia (Marhold et al., 2020). 
 
According to the consensus of the Asian Working Group on Sarcopenia in 2019, diagnostic criteria for 
sarcopenia include: dual-energy X-ray absorptiometry (DXA) measurement, with values less than 7.0 
kg/m2 for men and less than 5.4 kg/m2 for women; bioelectrical impedance analysis (BIA), with values 
less than 7.0 kg/m2 for men and less than 5.7 kg/m2 for women; decreased grip strength, less than 28 
kg for men and less than 18 kg for women; and reduced gait speed (less than 0.8 m/s). Computed 
tomography can detect muscle mass loss in cancer patients during the chemotherapy period (Oflazoglu 
et al., 2019). Sarcopenia can be classified into pre-sarcopenia, sarcopenia, and severe sarcopenia based 
on severity, with pre-sarcopenia indicating the presence of slow walking or reduced grip strength 
without muscle mass reduction. 

 
Domestic studies have shown that the prevalence of sarcopenia in men ranges from 4.0% to 23.6%, and 
in women, from 0.4% to 18.6% (Han, 2016; Chen et al., 2020). Studies on chemotherapy-induced 
sarcopenia have indicated associations with age ≥65 years, BMI < 25, Nutritional Risk Screening 
(NRS) 2002 score < 3. Sarcopenia occurred in 14.5% of patients during chemotherapy, 21.4% at the 
third month of chemotherapy, and 23% at six months (Oflazoglu et al., 2019). Approximately 35% of 
cancer patients have inadequate nutritional intake, leading to malnutrition-related increased mortality 
rates by 20% (Ryan et al., 2016). Therefore, it is recommended that cancer patients maintain a daily 
intake of 25-30 Kcal/kg/day and consume at least 1-1.5 g/kg of protein per day to reduce chemotherapy-
induced muscle mass loss (Ryan et al., 2016; Prado et al., 2020). 
 
Currently, research in Taiwan on sarcopenia primarily focuses on chronic diseases, with fewer studies 
investigating cancer-related sarcopenia. Cancer is the leading cause of death in Taiwan, with increasing 
incidence rates each year, emphasizing the importance of cancer cure and survival rates. Appropriate 
nutritional interventions for sarcopenia can reduce disability and cancer-related fatigue, improve quality 
of life, and increase survival rates in cancer patients. 
 
References: 
1. 
Fuchs, C.J., et al., Branched-chain amino acid and branched-chain ketoacid ingestion increases 
muscle protein synthesis rates in vivo in older adults: a double-blind, randomized trial. Am J Clin Nutr, 
2019. 110(4): p. 862-872. 
2. 
Martinez-Arnau, F.M., et al., Effects of Leucine Administration in Sarcopenia: A Randomized and 
Placebo-controlled Clinical Trial. Nutrients, 2020. 12(4). 
3. 
Neinast, M., D. Murashige, and Z. Arany, Branched Chain Amino Acids. Annu Rev Physiol, 2019. 
81: p. 139-164. 
4. 
Chou, P.Y. and G.D. Fasman, Structural and functional role of leucine residues in proteins. J Mol 
Biol, 1973. 74(3): p. 263-81. 
5. 
Shimomura, Y., et al., Regulation of branched-chain amino acid catabolism: nutritional and 
hormonal regulation of activity and expression of the branched-chain alpha-keto acid dehydrogenase 
kinase. Curr Opin Clin Nutr Metab Care, 2001. 4(5): p. 419-23. 
6. 
Laveneziana, P., et al., ERS statement on respiratory muscle testing at rest and during exercise. Eur 
Respir J, 2019. 53(6). 
7. 
Bashir, K.M.I. and J.S. Choi, Clinical and Physiological Perspectives of beta-Glucans: The Past, 
Present, and Future. Int J Mol Sci, 2017. 18(9). 
8. 
Shin, J.S., et al., Preventing effects of exopolymers purified from  (EAP) supplementation and 
resistance exercise on muscle aging and loss in the Korean elderly: a randomized controlled trial (vol 
13, pg 237, 2021). Toxicology and Environmental Health Sciences, 2021. 13(4): p. 429-429. 
9. 
Choi, J.S., et al., Antiosteoporotic effects of Polycan in combination with calcium lactate-
gluconate in ovariectomized rats. Exp Ther Med, 2014. 8(3): p. 957-967. 
10. Lim, J.M., et al., Extracellular polysaccharides purified from Aureobasidium pullulans SM‑2001 
(Polycan) inhibit dexamethasone‑induced muscle atrophy in mice. Int J Mol Med, 2018. 41(3): p. 1245-
1264.