AgingPhase 1/2NCT07469475
Effect of a Daily Supplement on Plasma PAI-1 Levels
A Phase 1/2 study testing Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puama in people with Aging and Endothelial Dysfunction, run by University of California, Los Angeles at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Aging, Endothelial Dysfunction, Senescence
- What is being tested?
- Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puama
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Feb 2026to Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- People of any gender at least 18 years of age who do not have a history of acute or chronic cardiovascular illnesses are eligible.
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
UCLA
Los Angeles, California, 90034
UCLA The Men's Clinic
Santa Monica, California, 90403
About this study
Official title: Effect of a Daily Nitric Oxide-Stimulating Supplement on Plasma PAI-1 Levels: a Six-Week, Open-Label Clinical Trial
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.
Read the detailed description
This study examines the effect of six weeks of daily supplementation on a panel of blood markers associated with vascular aging and inflammation.
The blood markers Plasminogen Activator Inhibitor-1 (PAI-1), Interleukin-8 (IL-8), Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), Fibroblast Growth Factor 23 (FGF-23), C-Reactive Protein (CRP), and Klotho will be measured. PAI-1 is a protein involved in blood clotting whose elevated levels are associated with increased cardiovascular risk and aging. IL-8 is a pro-inflammatory cytokine linked to chronic inflammation. PCSK9 is involved in lipid metabolism and cardiovascular risk. FGF-23 is a regulator of phosphate metabolism and vascular calcification. CRP is a general marker of system inflammation, and Klotho is an anti-aging protein with protective effects on vascular and renal function.
By assessing these markers, this study seeks to determine whether a natural oral supplement can modulate key pathways involved in vascular inflammation and aging, potentially positioning it as a natural oral supplement that may support vascular health in the context of age-related decline.
- Conditions
- Aging, Endothelial Dysfunction, Senescence
- Being tested
- Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puama
- Keywords
- Endothelial Dysfunction, Senescence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puamaDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puama |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The blood marker Interleukin-8 (IL-8) will be measured through a standard blood draw. IL-8 is a pro-inflammatory cytokine linked to chronic inflammation. Measurement units are pg/mL.
Measured: 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
The blood marker Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) will be measured through a standard blood draw. PCSK9 is involved in lipid metabolism and cardiovascular risk. Measurement units are ng/mL.
Measured: 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
The blood marker Fibroblast Growth Factor 23 (FGF-23) will be measured through a standard blood draw. FGF-23 is a regulator of phosphate metabolism and vascular calcification. Measurement units are pg/mL.
Measured: 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
The blood marker C-Reactive Protein (CRP) will be measured through a standard blood draw. CRP is a general marker of systemic inflammation. Measurement units are mg/dL.
Measured: From enrollment to the end of treatment at 6 weeks +/- 7 days
Change in Blood Level of Klotho Between Baseline and 6 Months
The blood marker Klotho will be measured through a standard blood draw. Klotho is an anti-aging protein with protective effects on vascular and renal function. Measurement units are pg/mL.
Measured: From enrollment to the end of treatment at 6 weeks +/- 7 days
Change in Blood Pressure Between Baseline and 6 Months
Systolic and diastolic blood pressure will be measured. Measurement units are mm Hg.
Measured: From enrollment to the end of treatment at 6 weeks +/- 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2026
- Study start24 Feb 2026
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sriram Eleswarapu, University of California, Los Angeles
- Investigators
- Sriram V Eleswarapu, MD, PhD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07469475
- Sponsor's protocol ID
- IRB #25-1948
- Status last verified
- Jun 2026
- First submitted
- 5 Mar 2026
- Last updated
- 25 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29732286Papamichael 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.
PubMed 15799717Haptonstall 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.
PubMed 32734819Whisner 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.
PubMed 31684015
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of a Daily Nitric Oxide-Stimulating Supplement on Plasma PAI-1 Levels: a Six-Week, Open-Label Clinical Trial
- ClinicalTrials.gov ID
- NCT07469475
- Acronym / sponsor ID
- IRB #25-1948
- Conditions
- Aging, Endothelial Dysfunction, Senescence
- Keywords
- Endothelial Dysfunction, Senescence
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- 24 Feb 2026 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 13 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study examines the effect of six weeks of daily supplementation on a panel of blood markers associated with vascular aging and inflammation.
The blood markers Plasminogen Activator Inhibitor-1 (PAI-1), Interleukin-8 (IL-8), Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), Fibroblast Growth Factor 23 (FGF-23), C-Reactive Protein (CRP), and Klotho will be measured. PAI-1 is a protein involved in blood clotting whose elevated levels are associated with increased cardiovascular risk and aging. IL-8 is a pro-inflammatory cytokine linked to chronic inflammation. PCSK9 is involved in lipid metabolism and cardiovascular risk. FGF-23 is a regulator of phosphate metabolism and vascular calcification. CRP is a general marker of system inflammation, and Klotho is an anti-aging protein with protective effects on vascular and renal function.
By assessing these markers, this study seeks to determine whether a natural oral supplement can modulate key pathways involved in vascular inflammation and aging, potentially positioning it as a natural oral supplement that may support vascular health in the context of age-related decline.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Supplement | Experimental | Dietary Supplement: Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puamaAll subjects recruited in this study will be in the experimental group receiving the oral supplement to consume twice daily for 42 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- People of any gender at least 18 years of age who do not have a history of acute or chronic cardiovascular illnesses are eligible.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puamaParticipants will consume a supplement called RM, which is composed of ginger extract, L-citrulline, and the herbal components Paullinia cupana and muira puama. | Dietary supplement | Supplement |
Primary outcome
Change in Blood Level of Plasminogen Activator Inhibitor-1 Between Baseline and 6 Months
Time frame: From enrollment to the end of treatment at 6 weeks +/- 7 days
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.
6 secondary outcomes
Change in Blood Level of Interleukin-8 Between Baseline and 6 Months
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From enrollment to the end of treatment at 6 weeks +/- 7 days
Change in Blood Level of Klotho Between Baseline and 6 Months
Time frame: From enrollment to the end of treatment at 6 weeks +/- 7 days
Change in Blood Pressure Between Baseline and 6 Months
Time frame: From enrollment to the end of treatment at 6 weeks +/- 7 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Background: PubMed 29732286Nguyen 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.
- Background: PubMed 15799717Papamichael 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.
- Background: PubMed 32734819Haptonstall 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.
- Background: PubMed 31684015Whisner 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sriram V Eleswarapu, MD, PhD principal investigator
University of California, Los Angeles
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puama in people with Aging and Endothelial Dysfunction, run by University of California, Los Angeles at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Blood Level of Plasminogen Activator Inhibitor-1 Between Baseline and 6 Months (time frame: From enrollment to the end of treatment at 6 weeks +/- 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07469475, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.