A Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy of Eleutherococcus Senticosus for Anti-inflammation and Improvement of Erythropoietin Hyporesponsiveness in Subjects Under Renal Dialysis
Phase: NA
Conditions: Renal Dialysis
Sponsor: Chung Shan Medical University

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A Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy 
of Eleutherococcus Senticosus for Anti-inflammation and Improvement of 
Erythropoietin Hyporesponsiveness in Subjects Under Renal Dialysis 
Study Objectives   
The purpose of this study was to investigate the efficacy of the oral Eleutherococcus 
Senticosus extract on anti-inflammation and improvement of erythropoietin hyporesponsiveness in 
renal dialysis patients. Inflammation indicators, anemia indicators, and health indicators will be 
evaluated and compared between the experimental and placebo groups. Safety data and adverse 
events will also be assessed and compared between the two groups. 
Study Design  
This is a randomized, double-blind, placebo-controlled, parallel comparison trial to evaluate 
the efficacy and safety of Eleutherococcus Senticosus taken orally by patients under regular dialysis. 
Eligible subjects with written consent were randomized into one of the two groups: A. 
Acanthopanax senticosus (30mg/vial); B. Placebo. After 2-4 weeks of run-in period, the study 
subjects were asked to take the investigational products orally for 90 days in order to evaluate the 
effects of oral Eleutherococcus Senticosus liquid on the markers of inflammation, anemia, and 
safety, and to compare the efficacy between oral Acanthopanax senticosus and placebo groups. 
  
Group 
Condition 
Sample size 
A 
Acanthopanax senticosus (30mg/vial) 
10 
B 
Placebo 
10 
Inclusion Criteria 
1. 
Under regular dialysis for at least 3 months 
2. 
Hemoglobin (Hb) <11 g/L after regular Erythropoietin (EPO) treatment 
3. 
Subjects with written informed consent form 

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Exclusion Criteria   
1. Use of steroid or high dose of antiplatelet drug (e.g. Aspirin >300mg) within one month 
2. Had surgery, myocardial infarction, or tumor within 12 weeks 
3. Currently use of antibiotic treatment for acute infection 
4. Pregnant women 
5. Reticulocyte>40 x 10^9 
6. Anemia (ferritin <100ng/mL and Transferrin Saturation (TSAT) <20%) 
7. Urea reduction ratio <65% or single pool Kt/V < 1.0 (hemodialysis patients) or total weekly 
Kt/V<1.7 (peritoneal dialysis patients) 
8. Sudden change of eating habit within one month 
9. Expected life less than six months or with unstable medical conditions 
10. Known history of allergic reaction to the investigational products 
11. With acute diseases and judged by the investigator to be ineligible to participate 
12. Received melatonin, androgen therapy or blood transfusion within two months 
13. Received any trial medications within 30 days 
When the subject withdraws from the study for any reason, the researcher should try his best to 
understand the reason why any subject withdraws, and the relevant information should be recorded 
in the case report, and the researcher still needs to encourage all the subjects to complete the last 
visit. All assessments help to understand or identify measures to avoid untoward effects and to seek 
appropriate solutions to any difficulties. 
Investigational Product 
Acanthopanax senticosus (30mg/vial) and Fructus Ziziphi Jujube concentrated juice15ml/vial 
used in this study were manufactured and provided by Direct Biotechnology Corp. Using Fructus 
Ziziphi Jujube concentrated juice15ml/vial as placebo is to make it the same flavor as the 
experimental group. The investigational product has been tested by SGS for nutritional composition 
analysis, which confirms that this product has very low potassium and phosphorus content, which is 

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extremely safe for patients with dialysis. 
Suggesting use:  
One bottle daily, can be taken before and after meals. Take a small bite in the mouth for a 
while before swallowing. Do not drink water for 20 minutes after consumption to achieve the fastest 
absorption. Patients with hyperacidity and gastroesophageal reflux are recommended to take it after 
meals.  
Available size: 15ml x 10 bottles  
Outcome measures  
Laboratory tests including indicators of inflammation, anemia, nutritional status, health status 
and safety, as well as blood pressure, heartbeat, weight will be tested during the screening period 
(before consumption) and three months after consumption. The subject's subjective self-assessment 
questionnaire for the investigational products was completed at each visit after the initiation of 
consumption. The subjects will also be required to inform the researcher of any adverse events at 
any time during the study and accept the necessary treatment to ensure the subject safety. 
Primary Outcomes 
(1) Total used amount of Erythropoietin (EPO) 
(2) Inflammation indicators: C reactive protein (CRP), Tumor necrosis factors 
(TNF-α), interleukin-6 (IL-6), interleukin-1 (IL-1) 
(3) Anemia indicators: hemoglobin (Hb), hematocrit (Hct), red blood cell (RBC) count, reticulocyte 
count 
Secondary Outcomes  
(4) Nutritional status: albumin, prealbumin, ferritin, Transferrin saturation, TSAT=serum Fe/TIBC, 
Total Iron Binding Capacity (TIBC) 
(5) Health status: body mass index (BMI), total cholesterol (TC), high density 
lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), fasting glucose, 
vital signs 

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Safety evaluations 
(6) GOP, GPT, creatinine, blood K, blood P, intact parathyroid hormone (iPTH)  
Vital signs and body weight 
Blood pressure and heart beats will be measured twice after at least 5 minutes rest at every 
visit with 5 minutes interval, and the average values will be recorded. Body weight and height will 
also be assessed at each visit.  
Subject's subjective self-assessment questionnaire  
The subjective assessment of the test subject was evaluated with a self-administered 
questionnaire:  
1. As of now, test products are positive for your condition?    □Yes  □No 
List the positive effects of test products on your body? _________________________ 
2. As of now, test products for adverse effects on your body?  □Yes  □No 
List the adverse effects of test products on your body? _________________________ 
Study flow chart 
Renal dialysis is a regular process. Patients will return to the hospital regularly for dialysis. In 
addition to the necessary medical treatment, each time they return to the clinic, they will be issued 
with the needed amount of the investigational products before the next visit, and the empty bottles 
and records will be collected. Other important follow-up time points are as follows:  
Visit 
1 
2 
3 
4 
Week 
-2~-4 
0 
4 
13 
Day 
-14~-30 
0 
30±3 
90±3 
Informed Consent 
X 
 
 
 
Medical History 
X 
 
 
 
Eligibility  
X 
X 
 
 
All evaluated indicators/Lab tests 
X 
 
 
X 
Blood pressure, height and weight 
X 
X 
X 
X 
Dispense Study Product 
 
X 
X 
X 
Accountability 
 
 
X 
X 

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Concomitant medication 
X 
X 
X 
X 
Patient Questionnaire / Adverse Event 
 
 
X 
X 
Note:  
1. If Hb is still lower than 8g / L after receiving conventional erythropoietin treatment and test 
products, blood transfusion treatment should be given  
2. The clinical care aims to maintain the subject's hemoglobin at 11-12 g / L  
3. Dates and doses of subjects receiving blood transfusions or iron during the trial must be 
recorded. 
Statistical Analysis  
Means and standard deviation are presented for continuous data, while frequency and 
percentage are used for categorical variables. All laboratory and vital evaluations were then 
compared between the two groups using the Mann-Whitney U test. Fisher’s exact test was 
performed for comparison of categorical variables. The Wilcoxon signed-rank test was performed to 
compare the values at baseline and 3 months after the initiation of product administration to each 
group. Statistical analyses were conducted by the study statistician with SPSS Version 18.0 for 
Windows (SPSS Inc., Chicago, IL, USA). A p-value less than 0.05 was considered to be statistically 
significant.