Clinical trial NCT06236243: Effect of Korean Red Ginseng Extract on Blood Flow in Healthy Adults
Official title: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Study the Effect of G1899 (Korean Red Ginseng Extract Powder) on Blood Flow in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
Blood Pressure Disorders
Vasodilation
Platelet Aggregation
Keywords: Blood Circulation
Lead sponsor: Korea Ginseng Corporation
Sponsor class: INDUSTRY
Collaborators: name: Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
First posted: 2024-02-01
Enrollment: 108
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Parallel, Placebo-Controlled
Primary purpose: BASIC_SCIENCE

Brief summary: The objectives of this clinical trial are to 1) determine the effect of the TP compared to placebo on blood flow and platelet aggregation, 2) to determine the effect of the TP on cardiovascular health compared to a placebo and 3) to assess the safety and tolerability of the TP in healthy adults.

Detailed description: Platelet aggregation and optimal blood flow are crucial for maintaining overall health. Platelet aggregation is necessary in order to form blood clots, essential for preventing excessive bleeding after injury. However, excessive aggregation can lead to the formation of blood clots within blood vessels, which can progress to cardiovascular complications. Further, efficient blood flow ensures the delivery of oxygen, nutrients and immune cells to various tissues and organs throughout the body to maintain cellular functions and organ health. Disruption in platelet aggregation and blood flow are associated with cardiovascular diseases (CVD) such as coronary artery disease, heart failure, vascular disease, dyslipidemia and high blood pressure which are the leading cause of death in adults. Risk factors for CVD include oxidative stress, diabetes, smoking, obesity, and lack of physical activity.

Intervention strategies such as lifestyle modifications and medications are often implemented for managing of CVD risk. However, there is an increasing interest in preventative measures such as dietary supplements, that may have protective properties against CVD through improving factors such as platelet aggregation and blood flow.

Panax ginseng, the dry root and rhizome of the Araliaeae ginseng plant, is considered an adaptogen known to help the body adapt to various stressors and promote overall wellbeing. The benefits of ginseng are thought to be in part from ginsenosides, a class of bioactive ingredients found in the plant. Ginsenosides have been suggested to improve blood flow through enhancing production of nitric oxide (NO) and vasodilation, thereby protecting against cardiovascular dysfunction. Only few randomized controlled trials have investigated the efficacy of ginseng on risk factors of CVD. Both Korean red ginseng root and Korean red ginseng ginsenoside extract have been shown to significantly improve flow-mediated dilation, a measure of endothelial function, when compared to a control at 180-minute post-dose. However, further research is needed to confirm the vasodilating capabilities of panax ginseng.

The present study is a randomized, double-blind, placebo-controlled clinical trial to investigate the effects of a panax ginseng supplement on cardiovascular health in healthy adults. The primary objective of this study is to explore the ability of panax ginseng to improve markers of blood flow and platelet aggregation compared to a placebo.

Efficacy outcomes include flow-mediated dilation (FMD), augmentation index (AI), platelet aggregation, and blood coagulation markers, lipids, blood pressure and endothelial function as assessed by log-transformed reactive hyperemia index (lnRHI) and blood levels of high sensitivity C-reactive protein (hs-CRP), NO and cyclic guanosine monophosphate (cGMP). These parameters will be assessed at baseline, interim, and end of study (EOS) visits. The study will last up to 16 weeks for each participant. The study will include a screening visit followed by a screening period lasting up to 28 days in duration, a baseline visit on Day 1, and 84 ± 3 days of study product use, followed by an EOS visit on the day after (Day 85 ± 3). The study will include a total of 4 in-person visit days: screening (Visit 1), baseline (Visit 2), interim (Visit 3), and EOS (Visit 4).

Eligibility criteria: Inclusion Criteria:

* Healthy adults (male and female) who are 20 to 75 years of age (inclusive).
* Are able to swallow tablets whole.
* In good general health (i.e., no uncontrolled diseases or conditions) as deemed by the investigator.
* Have acceptable heart rate as assessed by the investigator at screening and baseline.
* Have acceptable levels of blood lipid biomarkers at screening:

  * Triglycerides \<200 mg/dL
  * Total cholesterol \<240 mg/dL
  * LDL cholesterol \<160 mg/dL
  * HDL cholesterol \>39 mg/dL (for males) or \>49 mg/dL (females)
* Have resting (seated) systolic blood pressure between 90 to 129 mmHg and diastolic blood pressure between 60 to 79 mmHg (inclusive) at screening and baseline.
* Have a body mass index (BMI) between 18.0 to 34.9 kg/m\^2 (inclusive) at screening.
* Agrees to follow restriction on concomitant treatments as described in the study protocol.
* Agrees to use acceptable contraceptive methods for the study.
* Agrees to follow the restrictions on lifestyle as described in the study protocol.
* Have maintained consistent dietary habits (including supplement intake) and lifestyle for the last 3 months before screening.
* Willing and able to agree to the requirements of this study, be willing to give voluntary consent, and carry out all study-related procedures.

Exclusion Criteria:

* Are lactating, pregnant or planning to become pregnant during the study (e.g., positive pregnancy test at Visit 2).
* Have a known sensitivity, intolerability, or allergy to any of the study products or their excipients (including lactose).
* Have positive medical history of heart disease/cardiovascular disease, kidney disease (dialysis or renal failure), blood or bleeding disorder, hepatic impairment or disease, thyroid disease, or Type I or Type II diabetes.
* Has an abnormality or obstruction of the gastrointestinal tract precluding swallowing (e.g., dysphagia) and digestion (e.g., known intestinal malabsorption, celiac disease, inflammatory bowel disease, steatorrhea).
* Have medical condition(s) known to interfere with absorption, distribution, metabolism, or excretion of the study product (e.g., Crohn's disease, short bowel, acute or chronic pancreatitis, or pancreatic insufficiency).
* Have a positive medical history of immune disorder or is immunocompromised (i.e., HIV/AIDS, Systemic Lupus Erythematosus, etc.), or a history of cancer (except localized skin cancer without metastases or in situ cervical cancer) within 5 years prior to screening visit.
* Have a positive medical history of psychiatric disorder that required hospitalization in the prior year.
* Report a clinically significant illness during the 28 days before the first dose of study product.
* Have undergone major surgery in 3 months prior to screening or planned major surgery during the study.
* Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), chronic use defined as being taken more than 3 times a week for more than 3 months.
* Have a history of alcohol or substance abuse in the 12 months prior to screening (including having been hospitalized for such in an in-patient or out-patient intervention program).
* Current enrolment or past participation in another study with any product(s) with at least one active ingredient within 28 days before first dose of study product or longer, if the previous test product is deemed by the investigator to have lasting effects that might influence the eligibility criteria or outcomes of current study.
* Living in the same household as another currently/previously enrolled participant in the present study.
* Any other medical condition/situation or use of medications/supplements/therapies that, in the opinion of the investigator, may adversely affect the participant's ability to participate in the study or its measures or pose a significant risk to the participant.

Primary outcomes:
measure: Blood Flow
timeFrame: 6 weeks
measure: Blood Flow
timeFrame: 12 weeks
measure: Platelet Aggregation
timeFrame: 12 weeks
Secondary outcomes:
measure: Augmentation Index
timeFrame: 6 weeks
measure: Augmentation Index
timeFrame: 12 weeks
measure: Blood Levels of Nitric Oxide
timeFrame: 6 weeks
measure: Blood Levels of Nitric Oxide
timeFrame: 12 weeks
measure: Blood Levels Cyclic Guanosine Monophosphate (cGMP)
timeFrame: 6 weeks
measure: Blood Levels of cGMP
timeFrame: 12 weeks
measure: Systolic Blood Pressure (SBP) at rest (seated and supine)
timeFrame: 6 weeks
measure: SBP at rest (seated and supine)
timeFrame: 12 weeks
measure: Diastolic Blood Pressure (DBP) at rest (seated and supine)
timeFrame: 6 weeks
measure: DBP at rest (seated and supine)
timeFrame: 12 weeks
measure: Serum Levels of Triglycerides (TGs)
timeFrame: 6 weeks
measure: Serum Levels of TGs
timeFrame: 12 weeks
measure: Serum Levels of Low-density lipoprotein (LDL) cholesterol
timeFrame: 6 weeks
measure: Serum Levels of LDL cholesterol
timeFrame: 12 weeks
measure: Serum Levels of High-density lipoprotein (HDL) cholesterol
timeFrame: 6 weeks
measure: Serum Levels of HDL cholesterol
timeFrame: 12 weeks
measure: Serum Levels of Total Cholesterol
timeFrame: 6 weeks
measure: Serum Levels of Total Cholesterol
timeFrame: 12 weeks
measure: Endothelial Function
timeFrame: 6 weeks
measure: Endothelial Function
timeFrame: 12 weeks
measure: Blood levels of high-sensitivity C-reactive protein (hs-CRP)
timeFrame: 6 weeks
measure: Blood levels of hs-CRP
timeFrame: 12 weeks
measure: Blood Coagulation assessed by Prothrombin Time (PT)
timeFrame: 12 weeks
measure: Blood Coagulation assessed by Activated Partial Thromboplastin Time (aPTT)
timeFrame: 12 weeks
measure: Blood Coagulation assessed by Thromboxane B2
timeFrame: 12 weeks
measure: Heart Rate
timeFrame: 12 weeks
measure: Blood Pressure
timeFrame: 12 weeks
measure: Body Weight
timeFrame: 12 weeks
measure: Body Mass Index (BMI)
timeFrame: 12 weeks
measure: Whole Blood Hemoglobin
timeFrame: 12 weeks
measure: Whole Blood Hematocrit
timeFrame: 12 weeks
measure: Whole Blood Red Blood Cell Count
timeFrame: 12 weeks
measure: Whole Blood Red Blood Cell Distribution Width
timeFrame: 12 weeks
measure: Whole Blood Mean Corpuscular Volume
timeFrame: 12 weeks
measure: Whole Blood Mean Corpuscular Hemoglobin
timeFrame: 12 weeks
measure: Whole Blood Mean Corpuscular Hemoglobin Concentration
timeFrame: 12 weeks
measure: Whole Blood White Blood Cells
timeFrame: 12 weeks
measure: Whole Blood Neutrophils
timeFrame: 12 weeks
measure: Whole Blood Basophils
timeFrame: 12 weeks
measure: Whole Blood Eosinophils
timeFrame: 12 weeks
measure: Whole Blood Lymphocytes
timeFrame: 12 weeks
measure: Whole Blood Monocytes
timeFrame: 12 weeks
measure: Whole Blood Mean Platelet Volume (MPV)
timeFrame: 12 weeks
measure: Whole Blood Platelet Count
timeFrame: 12 weeks
measure: Serum Creatinine
timeFrame: 12 weeks
measure: Estimated Glomerular Filtration Rate (eGFR)
timeFrame: 12 weeks
measure: Serum Total Bilirubin
timeFrame: 12 weeks
measure: Serum Alkaline Phosphatase (ALP)
timeFrame: 12 weeks
measure: Serum Aspartate Transaminase (AST)
timeFrame: 12 weeks
measure: Serum Alanine Transaminase (ALT)
timeFrame: 12 weeks
measure: Serum Albumin
timeFrame: 12 weeks
measure: Serum Globulin
timeFrame: 12 weeks
measure: Serum Total Protein
timeFrame: 12 weeks
measure: Serum Chloride
timeFrame: 12 weeks
measure: Serum Sodium
timeFrame: 12 weeks
measure: Serum Potassium
timeFrame: 12 weeks
measure: Serum Fasting Glucose
timeFrame: 12 weeks
measure: Serum Urea
timeFrame: 12 weeks
measure: Adverse Events
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Tarzana
country: United States
facility: Valiance Clinical Research
state: California
Study officials:
affiliation: Valiance Clinical Research
name: Amir H.S. Rafie, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen J, Rizzo JA. The economics of cardiovascular disease in the United States. Crit Care Clin. 2012 Jan;28(1):77-88, vi. doi: 10.1016/j.ccc.2011.10.007.
citation: Hyun SH, Bhilare KD, In G, Park CK, Kim JH. Effects of Panax ginseng and ginsenosides on oxidative stress and cardiovascular diseases: pharmacological and therapeutic roles. J Ginseng Res. 2022 Jan;46(1):33-38. doi: 10.1016/j.jgr.2021.07.007. Epub 2021 Jul 26.
citation: Irfan M, Kwak YS, Han CK, Hyun SH, Rhee MH. Adaptogenic effects of Panax ginseng on modulation of cardiovascular functions. J Ginseng Res. 2020 Jul;44(4):538-543. doi: 10.1016/j.jgr.2020.03.001. Epub 2020 Mar 28.
citation: Liu L, Hu J, Mao Q, Liu C, He H, Hui X, Yang G, Qu P, Lian W, Duan L, Dong Y, Pan J, Liu Y, He Q, Li J, Wang J. Functional compounds of ginseng and ginseng-containing medicine for treating cardiovascular diseases. Front Pharmacol. 2022 Dec 2;13:1034870. doi: 10.3389/fphar.2022.1034870. eCollection 2022.
citation: Jovanovski E, Peeva V, Sievenpiper JL, Jenkins AL, Desouza L, Rahelic D, Sung MK, Vuksan V. Modulation of endothelial function by Korean red ginseng (Panax ginseng C.A. Meyer) and its components in healthy individuals: a randomized controlled trial. Cardiovasc Ther. 2014 Aug;32(4):163-9. doi: 10.1111/1755-5922.12077.
citation: Kang J, Lee N, Ahn Y, Lee H. Study on improving blood flow with Korean red ginseng substances using digital infrared thermal imaging and Doppler sonography: randomized, double blind, placebo-controlled clinical trial with parallel design. J Tradit Chin Med. 2013 Feb;33(1):39-45. doi: 10.1016/s0254-6272(13)60098-9.
citation: Rhee MY, Cho B, Kim KI, Kim J, Kim MK, Lee EK, Kim HJ, Kim CH. Blood pressure lowering effect of Korea ginseng derived ginseol K-g1. Am J Chin Med. 2014;42(3):605-18. doi: 10.1142/S0192415X14500396.