Browse > Article
http://dx.doi.org/10.25153/spkom.2022.26.3.009

Randomized, Double-blind, and Placebo-controlled a Clinical Study for Chronic Fatigue via the Analysis of Efficacy and Safety of Gongjin-dan and Ssanghwa-tang : Study Protocol  

Jun-Yong, Choi (Department of Korean Internal Medicine, Pusan National University Korean Medicine Hospital)
Byungmook, Lim (Division of Humanities and Social Medicine, School of Korean Medicine, Pusan National University)
Hyeun-kyoo, Shin (KM Science Research Division, Korea Institute of Oriental Medicine)
Kibong, Kim (School of Korean Medicine, Pusan National University)
Publication Information
Journal of Society of Preventive Korean Medicine / v.26, no.3, 2022 , pp. 97-108 More about this Journal
Abstract
Objectives : The purpose of this study is to confirm the efficacy and safety of Gongjin-dan and Ssanghwatang for chronic fatigue. Methods : A total of 90 people, between 19 and 65 years old, will be recruited to participate in a randomized, double-blind, and placebo-controlled a clinical trial. Participants in the Gongjin-dan group will take one pill of Gongjin-dan along with three packs of placebo oral liquid Ssanghwa-tang per day for 4 weeks. Participants in the Ssanghwa-tang group will take three packages of liquid Ssanghwa-tang and one placebo Gongjindan pill per day for 4 weeks. In the placebo group, participants will take one pill of placebo Gongjin-dan and three packs of placebo liquid Ssanghwa-tang per day, for 4 weeks. Outcomes will be measured at the baseline, 4th week, and 6th week. The primary outcome is the change in the Fatigue Severity Scale (FSS). Secondary outcomes are the change of Multidimensional Fatigue Inventory-20 (MFI-20), Chalder Fatigue Scale (CFQ), Short-Form 36 Health Survey (SF-36), Korean Version of Schedule of Fatigue and Anergy/General Physician (SOFA/GP), Glucose, Lactate, Ammonia, Free Fatty Acid (FAA), d-ROMs&BAP, Selenium, and Cortisol. Results : This trial was approved by the institutional review board of Pusan National University Korean Medicine Hospital (registry number: PNUKHIRB 2021-10-005). Recruitment opened in November 2021 and is supposed to be completed by December 2022. Conclusions : This trial will provide clinical information to determine the efficacy and safety of Gongjindan and Ssanghwa-tang for chronic fatigue.
Keywords
Gongjin-dan; Ssanghwa-tang; chronic fatigue; clinical trial; protocol;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Chung KI, Song CH. Clinical usefulness of fatigue severity scale for patients with fatigue, and anxiety or depression. Korean J Psychosom Med. 2001;9(2):164-73.
2 Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: A comprehensive approach to its definition and study. Ann Intern Med. 1994;121(12):953-9.   DOI
3 Kim CH, Shin HC, Won CW. Prevalence of chronic fatigue and chronic fatigue syndrome in Korea: community-based primary care study. J Korean Med Sci. 2005;20(4):529-34.   DOI
4 Centers Dis Control Prev. Treatment of ME/CFS [Internet]. Centers Dis Control Prev; 2018 [Updated 2021 Jan 28; cited 2022 Nov 30]. Available from: https://www.cdc.gov/me-cfs/treatment/
5 Chen R, Moriya J, Yamakawa JI, Takahashi T, Kanda T. Traditional Chinese medicine for chronic fatigue syndrome. Evid Based Complement Alternat Med. 2010;7(1):3-10.   DOI
6 Kim JW, Kim HJ, Jang ES, Jung HJ, Hwang MW, Nam DH. Survey on pattern identification and treatment of chronic fatigue in Korea medicine. JPPKM. 2018;32(2):126-33.   DOI
7 Moon E, Her Y, Lee JB, Park JH, Lee EH, Kim SH, Oh MS, Jang CG, Kim SY. The multi-herbal medicine Gongjin-dan enhances memory and learning tasks via NGF regulation. Neurosci Lett. 2009;466(3):114-9.   DOI
8 Choi KH, Park CS. An analysis of the Gongjindan's ingredients and its efficacy on antioxidation. Kor. J. Herbology. 2007;22(2):51-63.
9 Hong SS, Lee JY, Lee JS, Lee HW, Kim HG, Lee SK, Park BK, Son CG. The traditional drug Gongjindan ameliorates chronic fatigue in a forced-stress mouse exercise model. J Ethnopharmacol. 2015;168:268-78.   DOI
10 Sunwoo YY, Park SI, Chung YA, Lee J, Park MS, Jang KS, Maeng LS, Jang DK, Im R, Jung YJ, Park SA, Kang ES, Kim MW, Han YM. A pilot study for the neuroprotective effect of Gongjin-dan on transient middle cerebral artery occlusion-induced ischemic rat brain. Evid Based Complement Alternat Med. 2012;2012:682720.
11 Kim YH, Bae MJ. The effect of Gongjindan on the lipid metabolism in rats fed high fatdiet. J East-West Med. 1989;14(2):61-78.
12 Son MJ, Im HJ, Kim YE, Ku B, Lee JH, Son CG. Evaluation of the anti-fatigue effects of a traditional herbal drug, Gongjin-dan, under insufficient sleep conditions: study protocol for a randomised controlled trial. Trials. 2016;17:418.   DOI
13 Hwang SM, Chung DK. The effects of KongJindan (KJD) on the Alzheimer's disease model induced by CT105. J Orient Neuropsychiatry. 2004;15(2):103-18.
14 Jung HC, Jang HJ, Sung WY, Lee SH, Son JH, Han SH. A study of Gongjin-dan in patients with mild dementia of Alzheimer type. J Orient Neuropsychiatry. 2004;15(2):141-8.
15 Lee DS, Kim DW. A effect of Gongchen-dan to anemia. J Kyungwon Univ Korean Med Inst. 2004;7:97-107.
16 Nam DJ, Oh MS. Review about the study of Ssanghwa-tang published in Korea from 2000 to 2019. J Haehwa Med. 2019;28(2):12-9.
17 Lee JK, Lee NH, Ha HK, Lee HY, Seo CS, Jung DY, Lee JN, Shin HK. Analysis of studies on Ssanghwa-tang for establishment of evidence based medicine. Kor J Oriental Med. 2008;14(3):41-7.
18 Park JY, Hwang JG, Yun JK, Han KH, Do EJ, Kim SO, Kim MR. Effect of Ssanghwatang extract on antioxidant and anti-aging enzyme activities. Kor J Herbology. 2012; 27(3):67-74.   DOI
19 Kim DS, Um YR, Yang MC, Yun NY, Lee JH, Ma JY. Equivalence of traditional and individual preparation of Ssanghwa-tang in terms of polyphenol contents and radical scavenging activity. Kor J Oriental Med. 2011;17:169-72.
20 Sohn NW. Histochemical study for the effect of Ssanghwatang on the glycogen contents in liver and muscles of rats. Kor J Herbology. 1994;9:115-25.
21 Ann BN, Kim SK, Shim CK, Chung YB. Effect of a Chinese traditional medicine, Ssangwhatang, on the pharmacokinetics of sulfobromophthalein in the rats of hepatic failure induced by carbon tetrachloride. Yakhak Heoeji. 1984;28:207-15.
22 Kim YB, Kwon KB, Park JS, Park KH, Kim BR, Lee HS, Ryu DK. Gugissanghwa-tang water extract on the sexual behavior and serum testosterone concentration in male rats. Kor Soci Pathol. 199;13:152-7.
23 Jung D, Ha H, Lee HY, Lee JA, Lee JK, Huang DS, Shin HK. Stimulation of the immune response by Yin-tonifying formula. JKM. 2010;31(5):112-23.
24 Kim IH, Hwang GJ. Studies on the antiinflammatory activities of Ssanghwa-tang. Kor J Pharmaco. 1981;12:131-5.
25 Han DS, Lee HK, Gho HJ. Analgesic and anticonvulsionary effects of Ssanghwa-tang. Kor J Phamaco. 1983;14:60-3.
26 Ann C, Chae BY. Study of the effects of Ssangwha-tang on the antifatigue action and blood by repeated administration in mice. J Kyung Hee Kor Med. 1981;4:137-43.
27 Ha TY, Park DI. Effect of Ssanghwa-tang and Ssanghwa-tang-mixed-Paedoksan on the recovery of exercise induced fatigue. Kor J Life Sci. 1998;8(4):366-72.
28 Park WG, Park SD. Effects of Ssanghwatang on the antifatigue action and brain levels of norepinephrine, serotonin, 5- hydroxyindole-acetic acid and dopamine. J Jeahan Oriental Med Academy. 1995;1(1): 130-45.
29 Lee KO. A study of the effect of recruitment with a dosage of Ssanghwa-tang(雙和湯) after motor performance. KSSS. 1999:8(2);475-84.
30 Park SB, Kim KN, Sung E, Lee SY, Shin HC. Human placental extract as a subcutaneous injection is effective in chronic fatigue syndrome: A multi-center, double-blind, randomized, placebo-controlled study. Biol Pharm Bull. 2016;39(5):674-9.
31 Bang H, Ni L, Davis CE. Assessment of blinding in clinical trials. Control Clin Trials. 2004; 25(2):143-56.   DOI
32 Brown LF, Kroenke K, Theobald DE, Wu J. Symptom inventory in assessing cancerrelated fatigue. Supportive Care in Cancer. 2011:1255-59.
33 Cho JH, Son CG. Need for development of oriental medicine-derived systemic treatments against chronic fatigue-associated symptoms. JKM. 2009;30(4):28-36.
34 Sung WS, Kang HR, Jung CY, Park SS, Lee SH, Kim EJ. Efficacy of Korean red ginseng (Panax ginseng) for middle-aged and moderate level of chronic fatigue patients: A randomized, double-blind, placebo-controlled trial. Complement Ther Med. 2020;48:102246   DOI
35 Cella M, Chalder T. Measuring fatigue in clinical and community settings. J Psychosom Res. 2010;69(1):17-22.   DOI
36 Hadzi-Pavlovic D, Hickie IB, Wilson AJ, Davenport TA, Lloyd AR, Wakefield D. Screening for prolonged fatigue syndromes: validation of the SOFA scale. Soc Psychiatry Psychiatr Epidemiol. 2000;35(10):471-9.
37 Kim SS, Kim HJ, Lee SC, Yun SJ, Pack SH. Effect of sport massage on the blood lactate and LDH and glucose in recovery after exercise. Asian J Beauty Cosmetol. 2010;8(3):115-24.
38 Azevedo RA, Forot J, Iannetta D, Maclnnis MJ, Millet GY, Murias JM. Slight power output manipulations around the maximal lactate steady state have a similar impact on fatigue in females and males. J Appl Physiol. 2021;130(6):1879-92.   DOI
39 Wilkinson DJ, Smeeton NJ, Watt PW. Ammonia metabolism, the brain and fatigue; revisiting the link. Prog Neurobiol. 2010;91(3):200-19.   DOI
40 Blomstrand. Amino acids and central fatigue. Amino Acids. 2001;20(1):25-34.   DOI
41 Fukuda S, Nojima J, Motoki Y, Yamaguti K, Nakatomi Y, Okawa N, Fujiwara K, Watanabe Y, Kuratsune H. A potential biomarker for fatigue: Oxidative stress and anti-oxidative activity. Biol Psychol. 2016;118:88-93.   DOI
42 Powell JH, Liossi C, Moss-Morris R, Schlotz W. Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: A systematic review and subset meta-analysis. Psychoneuroendocrinology. 2013;38(11):2405-22.   DOI
43 Santos Vieira ML, Affonso Fonseca FL, Costa LG, Beltrame RL, Sousa Chaves CM, Cartum J, Alves SI, Azzalis LA, Junqueira VB, Pereria EC, Rocha KC. Supplementation with selenium can influence nausea, fatigue, physical, renal, and liver function of children and adolescents with cancer. J Med Food. 2015;18(1):109-17   DOI