Clinical trial NCT04069715: The Effect of Farlong® NotoGinseng™ (Ginseng Plus®) on Cholesterol and Blood Pressure
Official title: A Randomized, Placebo-controlled, Double-blind, Parallel Study to Determine the Effect of Farlong® NotoGinseng™ (Farlong® Ginseng Plus®) on Cholesterol and Blood Pressure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperlipidemias
Hypertension
Keywords: LDL-C
Blood pressure
triglycerides
HDL-C
total cholesterol
endothelial vasodilation
Hyperlipidemias
Hypertension
Lead sponsor: LongStar HealthPro, Inc. DBA Farlong Pharmaceutical
Sponsor class: INDUSTRY
Collaborators: name: Yunnan Panlong Yunhai Pharmaceutical Group Co., Ltd.
name: KGK Science Inc.
First posted: 2019-08-28
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a randomized, placebo-controlled, double-blind, parallel study with a 4-week therapeutic lifestyle change diet (TLC) run-in period and a 12-week supplementation period.
Primary purpose: SUPPORTIVE_CARE

Brief summary: In this randomized, placebo-controlled, double-blind parallel study in human participants with elevated LDL-C and elevated BP described here, the clinical benefits of Farlong NotoGinseng™ (Farlong Ginseng Plus® Panax Notoginseng extract), a product made of highly concentrated pharmaceutical grade notoginseng root extract, and containing high potency bioactive components, notoginsenoside, ginsenoside Rb1 and ginsenoside Rg1, will be investigated for its efficacy on LDL-C and blood pressure.

Detailed description: Health statistics include data on health disparities, global impact of cardiovascular diseases (CVDs) and risk factors including smoking, physical activity, body weight, cholesterol, blood sugar and blood pressure (BP) (1). Based on this, it is estimated that 33% of US adults had high blood pressure in 2009-2012 and during the same period, 43% of Americans had total cholesterol of 200 mg/dL or higher (2).

Chronic, elevated BP, defined as systolic BP (SBP) greater than 140 mmHg and diastolic BP (DBP) greater than 90 mmHg is clinically known as hypertension (3). Notably, hypertension is a strong, consistent, and independent risk factor for CVD and renal disease, including stroke, coronary heart disease, and kidney failure (4). Epidemiological evidence indicates that there is a log-linear relationship between elevated "bad" cholesterol, or low density lipoprotein-cholesterol (LDL-C) concentration, and relative risk of CVD (5). Lifestyle factors known to modify BP and cholesterol levels, including a balanced diet and exercise are not always met, highlighting the potential for nutritional supplementation.

The use of nutritional supplements, which might be effective in the reduction of high BP (hypertension) and hypercholesterolemia, is rapidly growing. However, most of the products available on the market have not been clinically evaluated for their effectiveness. Common ingredients found in cholesterol-lowering supplements include plant sterols. Plant sterols have been shown to reduce hypercholesterolemia in numerous experimental studies and in clinical trials, and are associated with lowering LDL-C by 10-15% (6;7). It has been estimated that consumption of at least 1.3 g of plant sterols/day may help to reduce the risk of heart disease by lowering blood cholesterol (8). Previous pre-clinical work reported that in addition to reduced cholesterol, supplementation with plant sterols can lower BP in hypertensive animals, although studies in humans are in early phases of development (9). Plant sterol supplementation may also improve vascular function, as one human trial found an association with sterol intake and lower levels of carotid wall thickness in older Amish participants (10).

Traditional Chinese Medicine has been used to treat cardiovascular diseases for thousands of years and species of the genus Panax plant are widely used in China and all over the world. Panax notoginseng (Burk.) F.H. Chen, is one of about 12 species in the Panax genus of the Araliaceae. Due to its sensitivity to light, P notoginseng is restricted to narrow geographic regions growing at an altitude of 1200-2000 m, primarily in the Wenshan mountains of Yunnan province in the People's Republic of China. The plant grows to a height of 30-60 cm and has dark green leaves branching from the stem where it typically bears a cluster of berries in the middle (11). The root of P notoginseng has a 400-year old history as a tonic and hemostatic drug; over 200 compounds have been isolated from this plant, exhibiting a variety of pharmacological effects, and appropriately enough the genus name "Panax" is derived from the Greek word (Pan = all + axos = medicine) meaning 'cure all' (12). Historically, Chinese medicine ascribes Panax ginseng C.A. Meyer to tonifying "qi", while P notoginseng nourishes the blood by dissipating blood stasis, inhibiting bleeding, enhancing circulation and alleviating pain. While the radix and rhizome of P notoginseng are used for bleeding disorders, the flower of this plant has been noted for several properties, including but not limited to, treating hypertension, and rejuvenating the liver (11). In the literature, extracts from P notoginseng have been referred to as Sanchitongshu, Xueshuantong, Sanqi or Tianqi and these ginsenosides from P notoginseng have collectively been referred to as Panax Notoginsenoside Saponins.

The primary bioactive ingredients in notoginseng plants are saponins, of which more than 60 have been identified (13). Saponins from notoginseng plant exert angiogenic effects by activating vascular endothelial growth factor and its receptor in downstream signaling pathways (14;15). Further, ginsenoside Rg5, a compound newly synthesized during the steaming process of notoginseng was found to promote angiogenesis and improve hypertension in animal models without adverse effects in the blood vasculature (16). Rg5 specifically increased phosphorylation of insulin-like growth factor-1 receptor (IGF-1R) resulting in stimulation of nitric oxide pathways to enhance angiogenesis (16). These studies suggest that notoginseng may have beneficial clinical applications in the management of CVD.

Currently, there is a lack of well-controlled trials evaluating the doses and effects of notoginseng (17). In this context, it is imperative to conduct well-controlled clinical trials that may unravel the mechanism (s) of action as well as evaluate the clinical potential of notoginseng as a natural health product and dietary supplement. In this randomized, placebo-controlled, double-blind parallel study in human participants with elevated LDL-C and elevated BP described here, the clinical benefits of Farlong NotoGinseng™ (Farlong Ginseng Plus® Panax Notoginseng extract), a product made of highly concentrated pharmaceutical grade notoginseng root extract, and containing high potency bioactive components, notoginsenoside, ginsenoside Rb1 and ginsenoside Rg1, will be investigated for its efficacy on LDL-C and BP.

Eligibility criteria: Inclusion Criteria:

1. Male and females age 18-75 years (inclusive)
2. BMI 23.0 to 32.5 kg/m2
3. Participants with LDL-C ≥2.6 mmol/L and \<3.8 mmol/L (≥ 100 mg/dL and \< 150 mg/dL)
4. Participants with pre-hypertension (systolic blood pressure of greater than or equal to 100 and less than 140 mmHg)
5. Participants agree to follow a therapeutic lifestyle changes (TLC) diet
6. If female, participant is not of child bearing potential, which is defined as females who have had a hysterectomy or oophorectomy, bilateral tubal ligation or are post-menopausal (natural or surgically with \> 1 year since last menstruation)

   OR

   Females of childbearing potential must agree to use a medically approved method of birth control and have a negative urine pregnancy test result. Acceptable methods of birth control include:
   * Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (DepoProvera, Lunelle), or hormone implant (Norplant System)
   * Double-barrier method (condoms with spermicide or diaphragm with spermicide)
   * Intrauterine devices
   * Vasectomy of partner (shown successful as per appropriate follow-up)
   * Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s)
7. Willing to maintain current physical activity patterns throughout the study
8. Willingness to complete questionnaires, records, and diaries associated with the study and to complete all clinic visits
9. Healthy as determined by laboratory results, medical history, and physical exam
10. Has given voluntary, written, informed consent to participate in the study

Exclusion Criteria:

1. History of allergic reaction or hypersensitivity to any of the study supplement components
2. Pregnant, breastfeeding, or planning to become pregnant during the course of the trial.
3. Use of cholesterol-lowering or blood pressure lowering prescription drugs within the last 6 months prior to randomization
4. LDL-C ≥ 3.37 mmol/L (130 mg/dL), if the 10-year risk of cardiovascular event is ≥ 20% as estimated by the Framingham risk score
5. LDL-C \> 3.5 mmol/L (135.34 mg/dL) OR if the total cholesterol vs. HDL-C ratio is \> 5.0 OR hs-CRP \> 2 mg/L in males \> 50 years and females \> 60 years, and if the 10-year Framingham risk score is 10-19%
6. Total cholesterol vs. HDL-C ratio \> 6.0, if the 10-year Framingham risk score is \< 10%
7. Use of ginseng-based drinks or products
8. Health supplements that affect blood pressure and cholesterol levels other than vitamins and minerals, such as plant sterols, omega-3, fish oil, soy protein, soluble oat fiber, psyllium seed husk, licorice or other blood pressure and cholesterol lowering nonprescription supplements within 1 month of enrollment and during the study
9. Persons on medications listed in section 4.3
10. BMI \> 32.5 kg/m2
11. Individuals with a history of coronary artery disease, previous myocardial infarction, peripheral vascular disease, atherosclerosis, diabetic men \> 45 years old, and diabetic women \> 50 years
12. Use of medicinal marijuana
13. History of chronic use of alcohol (\> 2 drinks/day) over the past 6 months
14. Currently smoking ≥ 20 cigarettes/day
15. Use of systemic antibiotics, corticosteroids, androgens, or phenytoin, and HRT (HRTs are allowed if participant has been on a stable dose for at least 3 months and intends to maintain their dosage regimen).
16. Significant or untreated medical disorders including uncontrolled diabetes, recent myocardial ischemia or infarction, unstable angina, peripheral vascular diseases/bruits, uncontrolled thyroid dysfunction, renal failure and serious renal diseases, chronic active hepatitis, acute hepatitis, cirrhosis of liver, AIDS, malignancy, recent cerebrovascular disease and neurological disorders or significant psychiatric illness
17. Unstable medical conditions
18. History of angina, congestive heart failure, inflammatory bowel disease, pancreatitis, gastrointestinal, renal, pulmonary, hepatic or biliary disease, autoimmune disorders or cancer (evidence of active lesions, chemotherapy or surgery in the past year)
19. Anticoagulant/ antiplatelet medications; see section 4.3 for concomitant medications that are exclusionary
20. Immunocompromised individuals
21. History of hemoglobinopathies such as sickle cell anemia, thalassemia, or sideroblastic anemia
22. Individuals who have followed the Therapeutic Lifestyle Changes (TLC) diet within 12 weeks of screening
23. Recent surgery or will be undergoing surgery that may have an effect on the study in the opinion of the Qualified Investigator
24. Participation in a clinical research trial within 30 days prior to randomization.
25. History of eating disorders.
26. Clinically significant abnormal laboratory results at screening
27. Exercise greater than 24 km (15 miles)/week or 4,000 kcal/week
28. Cognitively impaired and/or who are unable to give informed consent
29. Plan to donate blood during the study or within 30 days of completing the study
30. Any additional underlying medical or psychiatric condition, clinical disorder or laboratory finding, which in the opinion of the Qualified Investigator may interfere with study objectives

Primary outcomes:
measure: The Difference in Serum LDL-C From Baseline to Week 12 Between Farlong NotoGinseng™ (Farlong Ginseng Plus® Panax Notoginseng Extract) and Placebo After 12 Weeks of Supplementation.
timeFrame: 12 weeks
Secondary outcomes:
measure: 1. The Difference in Serum LDL-C From Baseline to Week 8 Between Farlong Notoginseng and Placebo
timeFrame: 8 weeks
measure: 2. The Difference in Blood Pressure From Baseline to Week 8 Between Farlong Notoginseng and Placebo
timeFrame: 8 weeks
measure: 3. The Difference in Blood Pressure From Baseline to Week 12 Between Farlong Notoginseng and Placebo
timeFrame: 12 weeks
measure: 4. The Difference in Triglycerides From Baseline to Week 8 Between Farlong Notoginseng and Placebo
timeFrame: 8 weeks
measure: 5. The Difference in Triglycerides From Baseline to Week 12 Between Farlong Notoginseng and Placebo
timeFrame: 12 weeks
measure: 6. The Difference in HDL-C From Baseline to Week 8 Between Farlong Notoginseng and Placebo
timeFrame: 8 weeks
measure: 7. The Difference in HDL-C From Baseline to Week 12 Between Farlong Notoginseng and Placebo
timeFrame: 12 weeks
measure: 8. The Difference in Total Cholesterol From Baseline to Week 8 Between Farlong Notoginseng and Placebo
timeFrame: 8 weeks
measure: 9. The Difference in Total Cholesterol From Baseline to Week 12 Between Farlong Notoginseng and Placebo
timeFrame: 12 weeks
measure: 10. The Difference in Endothelial Vasodilation, as Measured by the EndoPAT, From Baseline to Week 8 Between Farlong Notoginseng and Placebo
timeFrame: 8 weeks
measure: 11. The Difference in Endothelial Vasodilation, as Measured by the EndoPAT, From Baseline to Week 12 Between Farlong Notoginseng and Placebo
timeFrame: 12 weeks
Other outcomes:
Locations:
Study officials:
affiliation: KGK Science Inc.
name: David Crowley, MD
role: PRINCIPAL_INVESTIGATOR
References: