Effect of a Daily Supplement on Plasma PAI-1 Levels

NCT07469475 | Active Not Recruiting Phase 1

• 1 other identifier: IRB #25-1948
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

In a healthy person, the production of nitric oxide (NO) by the endothelium, the inner lining of the blood vessel, is responsible for a) the ability of the blood vessel to dilate so it can increase its blood flow and b) act as an anti-clotting product to prevent blood clotting in those vessels. Under physiological stress either due to the development of a disease such as diabetes or simply from aging, the endothelial cells can be impacted and become dysfunctional, thereby impairing their ability to make NO and even promoting the development of blood clots. When such endothelial dysfunction occurs, it may be a precursor for the future development of cardiovascular (CV) disease like hypertension or coronary artery disease later on in life in these patients. Therefore, the ability to enhance the local production or availability of NO within such affected blood vessels in patients identified as prone to endothelial dysfunction could play a positive role in either preventing or delaying the onset of endothelial dysfunction and subsequent CV disease in such patients. RM is an oral supplement consisting of natural ingredients and the amino acid, L-citrulline. In laboratory experiments with cells from the inner lining of blood vessels, the four components of RM have been shown to increase the concentration of NO and decrease the levels of some aging markers. In our recently completed study (manuscript currently in review), 31 young men and women took the supplement for 14 days and had no serious side effects. The supplement caused the expected potentially beneficial dilation of the blood vessels and decrease in the levels of Plasminogen Activator Inhibitor-1 (PAI-1), whose levels correlate with aging and risk of cardiovascular disease. In this study, healthy participants will consume the supplement for a 6-week period to determine if PAI-1 levels continue to be suppressed and also examine whether the supplement has an effect on other blood markers whose levels can change with aging or cardiovascular disease and may also be indicative or predictive of an illness.

Conditions

Aging; Endothelial Dysfunction; Senescence

Keywords

Endothelial Dysfunction; Senescence

Outcome Measures

Primary Outcomes (1)

• Change in Blood Level of Plasminogen Activator Inhibitor-1 Between Baseline and 6 Months

  Blood levels of Plasminogen Activator Inhibitor-1 (PAI-1), a marker that correlates with aging and risk of cardiovascular disease, will be measured through a standard blood draw. Measurement units are ng/mL.

  From enrollment to the end of treatment at 6 weeks +/- 7 days

Secondary Outcomes (6)

• Change in Blood Level of Interleukin-8 Between Baseline and 6 Months

  From enrollment to the end of treatment at 6 weeks +/- 7 days

• Change in Blood Level of Proprotein Convertase Subtilisin/Kexin Type 9 Between Baseline and 6 Months

  From enrollment to the end of treatment at 6 weeks +/- 7 days

• Change in Blood Level of Fibroblast Growth Factor 23 (FGF-23) Between Baseline and 6 Months

  From enrollment to the end of treatment at 6 weeks +/- 7 days

• Change in Blood Level of C-Reactive Protein Between Baseline and 6 Months

  From enrollment to the end of treatment at 6 weeks +/- 7 days

• Change in Blood Level of Klotho Between Baseline and 6 Months

  From enrollment to the end of treatment at 6 weeks +/- 7 days

Study Arms (1)

Supplement

EXPERIMENTAL

All subjects recruited in this study will be in the experimental group receiving the oral supplement to consume twice daily for 42 days.

Dietary Supplement: Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puama

Interventions

Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puama DIETARY_SUPPLEMENT

Participants will consume a supplement called RM, which is composed of ginger extract, L-citrulline, and the herbal components Paullinia cupana and muira puama.

Supplement

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• People of any gender at least 18 years of age who do not have a history of acute or chronic cardiovascular illnesses are eligible.

You may not qualify if:

• Younger than 18 years of age
• Currently pregnant (which will be confirmed by pregnancy test for participants capable of pregnancy)
• Using hormonal birth control
• Current smoker
• Allergy to ginger, muira puama, Paullinia cupana, or L-citrulline
• Previous use of Revactin® or RM
• History of serious cardiovascular events, including myocardial infarction (heart attack) or stroke
• History of coronary, cardiac, or carotid surgery such as a stent, heart surgery, or endarterectomy
• Active cancer of any type other than skin cancer

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (2)

UCLA

Los Angeles, California, 90034, United States

Location

UCLA The Men's Clinic

Santa Monica, California, 90403, United States

Location

Related Publications (4)

• Nguyen S, Rajfer J, Shaheen M. Safety and efficacy of daily Revactin(R) in men with erectile dysfunction: a 3-month pilot study. Transl Androl Urol. 2018 Apr;7(2):266-273. doi: 10.21037/tau.2018.03.22.

  PMID: 29732286 BACKGROUND

• Papamichael CM, Aznaouridis KA, Karatzis EN, Karatzi KN, Stamatelopoulos KS, Vamvakou G, Lekakis JP, Mavrikakis ME. Effect of coffee on endothelial function in healthy subjects: the role of caffeine. Clin Sci (Lond). 2005 Jul;109(1):55-60. doi: 10.1042/CS20040358.

  PMID: 15799717 BACKGROUND

• Haptonstall KP, Choroomi Y, Moheimani R, Nguyen K, Tran E, Lakhani K, Ruedisueli I, Gornbein J, Middlekauff HR. Differential effects of tobacco cigarettes and electronic cigarettes on endothelial function in healthy young people. Am J Physiol Heart Circ Physiol. 2020 Sep 1;319(3):H547-H556. doi: 10.1152/ajpheart.00307.2020. Epub 2020 Jul 31.

  PMID: 32734819 BACKGROUND

• Whisner CM, Angadi SS, Weltman NY, Weltman A, Rodriguez J, Patrie JT, Gaesser GA. Effects of Low-Fat and High-Fat Meals, with and without Dietary Fiber, on Postprandial Endothelial Function, Triglyceridemia, and Glycemia in Adolescents. Nutrients. 2019 Nov 2;11(11):2626. doi: 10.3390/nu11112626.

  PMID: 31684015 BACKGROUND

MeSH Terms

Interventions

ginger extract; Citrulline

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Sriram V Eleswarapu, MD, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Urology

Model Details: 35 healthy adult participants will be recruited. All participants will take the supplement twice daily for 6 weeks (42 days). Blood markers, blood pressure, and heart rate will be measured on day 0 and day 42.

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 13, 2026
• Study Start: February 24, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 25, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)