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Published in: Trials 1/2020

Open Access 01-12-2020 | Arterial Occlusive Disease | Study protocol

Efficacy of Hwangryunhaedok-tang (Huang-lian-jie-du-tang, Oren-gedoku-to) for patients with hyperlipidemia: a study protocol for a randomized, double-blind, placebo-controlled, parallel, investigator-initiated clinical trial

Authors: Boram Lee, Kyungsun Han, Hyo-Ju Park, Ae-Ran Kim, O-Jin Kwon, Changsop Yang, Chung-Sik Cho

Published in: Trials | Issue 1/2020

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Abstract

Background

The prevalence of hyperlipidemia continues to increase due to aging and lifestyle changes. Statins are currently used as the first choice for treating hyperlipidemia, but are limited by adverse reactions. Hwangryunhaedok-tang (HHT) has received attention as a promising intervention for hyperlipidemia through a few experimental and clinical trials. This study aims to explore the feasibility, effectiveness, and safety of HHT for hyperlipidemia treatment.

Methods

This is a study protocol for a randomized, double-blind, placebo-controlled, parallel, investigator-initiated, pilot clinical trial held in Daejeon, Republic of Korea. Thirty patients with hyperlipidemia will be randomly allocated to HHT or placebo granule groups in equal proportions. Participants will be administered HHT or placebo granules three times per day for 8 weeks and followed up for another 4 weeks. The primary outcome is low-density lipoprotein cholesterol at 8 weeks from the commencement of treatment. Other blood lipid parameters, biomarkers of atherosclerosis, the degree of arteriosclerosis, blood glucose parameters, blood pressure, anthropometric parameters, health-related quality of life, and the changes in the general symptoms of cold and hot patterns will be measured as secondary outcomes. Adverse events and laboratory test results will be investigated to assess the safety. Changes in the gut microbiome before and after intervention will also be assessed as an exploratory outcome through next-generation sequencing. Data will be recorded in electronic case report forms and analyzed using SAS® Version 9.4.

Discussion

This is a rigorously designed pilot clinical trial to explore the effect and safety of Hwangryunhaedok-tang compared to placebo control for patients with hyperlipidemia, thereby potentially facilitating better management of hyperlipidemia. The results of this pilot study could form the foundation for a future large-scale, confirmatory clinical trial.

Trial registration

Clinical Research Information Service KCT0004564. Registered on December 18, 2019
Appendix
Available only for authorised users
Literature
1.
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–421.
2.
Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139:e56–e528.CrossRef
3.
Korea Centers for Disease Control and Prevention. Korea Health Statistics 2017: Korea National Health and Nutrition Examination Survey (KNHANES VII-2). Cheongju: Korea Centers for Disease Control and Prevention; 2018. p. 238.
4.
Committee of Clinical Practice Guideline of the Korean Society Lipid and Atherosclerosis. Korean Guidelines for the Management of Dyslipidemia 4th ed. Seoul: The Korean Society of Lipid and Atherosclerosis; 2018.
5.
Kim HC, Oh SM. Noncommunicable diseases: current status of major modifiable risk factors in Korea. J Prev Med Public Health. 2013;46:165.CrossRef
6.
Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–78.CrossRef
7.
Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.CrossRef
8.
Guo M, Liu Y, Gao ZY, Shi DZ. Chinese herbal medicine on dyslipidemia: progress and perspective. Evid Based Complement Alternat Med. 2014;2014:163036.PubMedPubMedCentral
9.
Hong Y-K, Kim S-S, Shin M-K, Kim J-J. Review of Korean medical treatment in hyperlipidemia-focusing on treatment of Korean herbal medicine. J Physiol Pathol Korean Med. 2010;24:9–14.
10.
Jung WS, Kwon S, Cho SY, Park SU, Moon SK, Park JM, Ko CN, Cho KH. The effects of Chunghyul-Dan (a Korean medicine herbal complex) on cardiovascular and cerebrovascular diseases: a narrative review. Evid Based Complement Alternat Med. 2016;2016:2601740.PubMedPubMedCentral
11.
Moon S-K, Kim SB, Kwon S, Cho S-Y, Park S-U, Jung W-S, Park J-M, Ko C-N, Cho K-H. Anti-hypertensive effect by single adminstration of Chunghyul-dan: a case series. J Korean Med. 2018;39:95–103.CrossRef
12.
Kim YS, Jung EA, Shin JE, Chang JC, Yang HK, Kim NJ, Cho KH, Bae HS, Moon SK, Kim DH. Daio-Orengedokuto inhibits HMG-CoA reductase and pancreatic lipase. Biol Pharm Bull. 2002;25:1442–5.CrossRef
13.
Sekiya N, Kainuma M, Hikiami H, Nakagawa T, Kouta K, Shibahara N, Shimada Y, Terasawa K. Oren-gedoku-to and Keishi-bukuryo-gan-ryo inhibit the progression of atherosclerosis in diet-induced hypercholesterolemic rabbits. Biol Pharm Bull. 2005;28:294–8.CrossRef
14.
Wang Y, Zidichouski JA. Update on the benefits and mechanisms of action of the bioactive vegetal alkaloid berberine on lipid metabolism and homeostasis. Cholesterol. 2018;2018:7173920.CrossRef
15.
Ouyang X, Kuang Z, Wei W. Clinical research of Huanglian Jiedu decoction for intervention of dyslipidemia. J Guangzhou Univ Tradit Chin Med. 2015;32:993–5, 999.
16.
Xue Y, Yang X, Wu D, Ji G, Sun Y. Effects of Coptidis decoction for detoxification combined with rosuvastatin on inflammatory cytokines and adipokines in patients with essential hypertension complicated by hypercholesterolemia. Hebei Med J. 2018;40:2885–8, 2894.
17.
Cheng CW, Wu TX, Shang HC, Li YP, Altman DG, Moher D, Bian ZX. CONSORT Extension for Chinese Herbal Medicine Formulas 2017: recommendations, explanation, and elaboration. Ann Intern Med. 2017;167:112–21.CrossRef
18.
Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hrobjartsson A, Schulz KF, Parulekar WR, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586.CrossRef
19.
Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747–57.CrossRef
20.
Brotman DJ, Girod JP, Garcia MJ, Patel JV, Gupta M, Posch A, Saunders S, Lip GY, Worley S, Reddy S. Effects of short-term glucocorticoids on cardiovascular biomarkers. J Clin Endocrinol Metab. 2005;90:3202–8.CrossRef
21.
Bang H, Ni L, Davis CE. Assessment of blinding in clinical trials. Control Clin Trials. 2004;25:143–56.CrossRef
22.
Oh JY, Yang YJ, Kim BS, Kang JH. Validity and reliability of Korean version of International Physical Activity Questionnaire (IPAQ) short form. J Korean Acad Fam Med. 2007;28:532–41.
23.
24.
Bae KH, Yoon Y, Yeo M, Kim HS, Lee Y, Lee S. Development on the questionnaire of cold-heat pattern identification based on usual symptoms for health promotion-focused on agreement study. J Soc Prev Korean Med. 2016;20:17–26.
25.
Bae KH, Jang ES, Park K, Lee Y. Development on the questionnaire of cold-heat pattern identification based on usual symptoms: reliability and validation study. J Physiol Pathol Korean Med. 2018;32:341–6.CrossRef
26.
Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, Robson R, Thabane M, Giangregorio L, Goldsmith CH. A tutorial on pilot studies: the what, why and how. BMC Med Res Methodol. 2010;10:1.CrossRef
27.
Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat J Appl Stat Pharm Ind. 2005;4:287–91.
28.
Authors/Task Force Members; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. Atherosclerosis. 2019;290:140–205.
29.
National Institute of Food and Drug Safety Evaluation. Guidelines for clinical trials for hyperlipidemia treatment. Cheongju: Korean Ministry of Food and Drug Safety; 2015.
30.
Witt CM, Aickin M, Cherkin D, Che CT, Elder C, Flower A, Hammerschlag R, Liu JP, Lao L, Phurrough S, et al. Effectiveness guidance document (EGD) for Chinese medicine trials: a consensus document. Trials. 2014;15:169.CrossRef
31.
Pelkonen O, Xu Q, Fan TP. Why is research on herbal medicinal products important and how can we improve its quality? J Tradit Complement Med. 2014;4:1–7.CrossRef
32.
Kwon S, Jung W, Byun AR, Moon S, Cho K, Shin K. Administration of Hwang-Ryun-Haedok-tang, a herbal complex, for patients with abdominal obesity: a case series. Explore (NY). 2015;11:401–6.CrossRef
33.
Wouters K, Shiri-Sverdlov R, van Gorp PJ, van Bilsen M, Hofker MH. Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified ApoE and LDLR mice. Clin Chem Lab Med. 2005;43:470–9.CrossRef
34.
Chung CM, Tseng YH, Lin YS, Hsu JT, Wang PC. Association of brachial-ankle pulse wave velocity with atherosclerosis and presence of coronary artery disease in older patients. Clin Interv Aging. 2015;10:1369–75.CrossRef
35.
Hasimu B, Li J, Nakayama T, Yu J, Yang J, Li X, Hu D. Ankle brachial index as a marker of atherosclerosis in Chinese patients with high cardiovascular risk. Hypertens Res. 2006;29:23–8.CrossRef
36.
Soeki T, Sata M. Inflammatory biomarkers and atherosclerosis. Int Heart J. 2016;57:134–9.CrossRef
37.
Danesh J, Lewington S, Thompson SG, Lowe GD, Collins R, Kostis JB, Wilson AC, Folsom AR, Wu K, Benderly M, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005;294:1799–809.PubMed
38.
Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA. 1997;277:1775–81.CrossRef
39.
Doo HK, Park HJ. A pharmacological study of Whangryonhaedoktang. J Kyung Hee Orient Med Coll. 1982;5:103–14.
40.
Liu Y, Song X, Zhou H, Zhou X, Xia Y, Dong X, Zhong W, Tang S, Wang L, Wen S, et al. Gut microbiome associates with lipid-lowering effect of rosuvastatin in vivo. Front Microbiol. 2018;9:530.CrossRef
41.
Sun R, Yang N, Kong B, Cao B, Feng D, Yu X, Ge C, Huang J, Shen J, Wang P, et al. Orally administered berberine modulates hepatic lipid metabolism by altering microbial bile acid metabolism and the intestinal FXR signaling pathway. Mol Pharmacol. 2017;91:110–22.CrossRef
42.
Chai J. Clinical study of Huanglian Jiedu decoction on blood lipid disorders from the theory of small intestine secretion. Liaoning Univ Tradit Chin Med. 2017..
Metadata
Title
Efficacy of Hwangryunhaedok-tang (Huang-lian-jie-du-tang, Oren-gedoku-to) for patients with hyperlipidemia: a study protocol for a randomized, double-blind, placebo-controlled, parallel, investigator-initiated clinical trial
Authors
Boram Lee
Kyungsun Han
Hyo-Ju Park
Ae-Ran Kim
O-Jin Kwon
Changsop Yang
Chung-Sik Cho
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Trials / Issue 1/2020
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-020-04695-3

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