COMP-4 Supplementation for Endothelial Dysfunction

Overseen By Sriram V. Eleswarapu, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, Los Angeles

Must not be taking: Blood pressure medications

Disqualifiers: Pregnancy, Cardiovascular events, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether an oral supplement called COMP-4 can improve blood flow and reduce inflammation in blood vessels. By increasing nitric oxide, a molecule that helps blood vessels relax and prevents clotting, the supplement could help prevent future heart problems. The trial seeks healthy men and women aged 18-39 with no history of heart disease or related conditions. Participants will take COMP-4 for 14 days, and researchers will use ultrasound to check for blood flow improvements in the upper arm. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

If you are currently taking blood pressure medications, you cannot participate in this trial. The protocol does not specify about other medications, so it's best to discuss your specific situation with the trial organizers.

Is there any evidence suggesting that COMP-4 is likely to be safe for humans?

Research has shown that COMP-4 is a safe and well-tolerated oral supplement. Studies have found that it can increase nitric oxide production in blood vessel cells, potentially improving blood flow and reducing inflammation—both crucial for heart health.

COMP-4 has undergone laboratory testing and is already used in medical settings, indicating its general safety for people. The reviewed studies reported no major side effects or negative reactions. Therefore, individuals considering joining this clinical trial can feel more confident about the safety of COMP-4. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

COMP-4 is unique because it targets endothelial dysfunction with a novel approach. Unlike traditional treatments that often rely on medications aimed at managing symptoms or improving blood flow, COMP-4 is an oral supplement taken twice daily, potentially offering a more convenient and non-invasive option. Researchers are excited about its potential to produce results in just 14 days, which could provide a quicker response compared to the weeks or months often required with standard therapies.

What evidence suggests that COMP-4 might be an effective treatment for endothelial dysfunction?

Research shows that COMP-4, the investigational treatment in this trial, may increase the production of nitric oxide (NO) in the cells lining blood vessels. This is important because NO helps blood vessels relax and prevents clots. Studies also suggest that COMP-4 can repair damage from oxidative stress, making more NO available. Additionally, it might lower levels of substances like IL-8 and PAI-1, which are linked to blood vessel problems. In short, COMP-4 could improve blood flow and reduce inflammation, potentially helping to prevent heart and blood vessel diseases. ^{2 3 5 6 7}

Who Is on the Research Team?

Sriram V. Eleswarapu, MD PhD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for healthy men and women aged 18-39 without any history of serious cardiovascular events or illnesses that affect blood vessel dilation. Pregnant women, individuals on blood pressure medications, or those allergic to COMP-4 ingredients (ginger, muira puama, Paullinia cupana, L-citrulline) cannot participate.

Inclusion Criteria

All men and women ages 18-39 will be offered the opportunity to participate in this study as long as they do not have a history of acute or chronic cardiovascular illnesses affecting flow mediated dilation.

All men and women ages 18-39 will be offered the opportunity to participate in this study as long as they do not have a history of acute or chronic cardiovascular illnesses effecting flow mediated dilation.

Exclusion Criteria

Women who are currently pregnant

Those currently on blood pressure medications

Those with known allergies to any of the 4 components of COMP-4 (ginger, muira puama, Paullinia cupana, and L-citrulline)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person or virtual)

Treatment

Participants receive COMP-4 supplementation twice daily for 14 days

2 weeks

2 visits (in-person), 2 calls (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• COMP-4

Trial Overview

The study tests the effects of a supplement called COMP-4 on improving blood flow in arm vessels and reducing inflammatory markers linked to endothelial dysfunction. Participants will take COMP-4 for two weeks while undergoing non-invasive ultrasound measurements.

How Is the Trial Designed?

Group I: Experimental Group Experimental Treatment 1 Intervention

All subjects recruited in this study will be in the experimental group receiving the oral supplement, COMP-4, twice daily for 14 days.

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Published Research Related to This Trial

A 6-month supplementation of L-arginine significantly improved coronary blood flow response to acetylcholine in patients with nonobstructive coronary artery disease, indicating enhanced endothelial function.

The L-arginine treatment also led to a decrease in plasma endothelin levels and improved patient symptom scores, suggesting both efficacy and potential therapeutic benefits for coronary endothelial dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Lerman, A., Burnett, JC., Higano, ST., et al.[2019]

In a study involving 32 patients, the response of internal mammary arteries, radial arteries, and saphenous veins to phenylephrine was significantly influenced by nitric oxide levels, with the radial artery showing a lower contraction response compared to the other vessels.

The use of L-arginine increased the sensitivity to phenylephrine, while L-NAME decreased it, indicating that nitric oxide production plays a crucial role in modulating vascular responses in these arteries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Modification of phenylephrine induced contraction of human vessel rings by L-arginine and L-arginine methyl ester]. Prieto, JC., Pinardi, G., Zamorano, J., et al.[2013]

A dietetic product combining L-arginine with vitamins B6, B12, and folic acid significantly improved endothelial function in individuals with mild to moderate blood pressure elevation, as shown by a notable increase in the reactive hyperaemia index after 3 months compared to placebo.

The intervention also led to reductions in blood pressure and plasma homocysteine levels, with no serious adverse events reported, confirming its safety and efficacy for dietary management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation. Menzel, D., Haller, H., Wilhelm, M., et al.[2018]

L-arginine supplementation (6-8 g/day) can improve endothelial function and lower blood pressure, particularly in individuals with significant endothelial dysfunction or arginine deficiency.

The long-term effects of L-arginine on delaying atherosclerosis progression and reducing cardiovascular risks remain uncertain, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-Arginine and vascular health. Ströhle, A., von Bibra, H., Hahn, A.[2018]

Chronic use of oral antioxidants has shown positive effects on endothelial function, particularly in improving conduit vessel dilation and reducing endothelial cell-monocyte interactions, based on a review of patient studies.

However, the effects on resistance vessels were mostly negative, indicating that while antioxidants may benefit certain aspects of endothelial dysfunction, their overall impact on vascular health needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic antioxidant use and changes in endothelial dysfunction: a review of clinical investigations. Aminbakhsh, A., Mancini, J.[2022]

Endothelial dysfunction is an early indicator of cardiovascular disease and is associated with risk factors like hypertension, high cholesterol, diabetes, and smoking, suggesting that addressing these conditions can improve heart health.

Lifestyle changes, dietary modifications, and certain medications, such as ACE inhibitors and lipid-lowering agents, can enhance endothelial function, indicating potential pathways for preventing cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implications of endothelial dysfunction. Pepine, CJ.[2020]

Endothelial function measurement is becoming an important tool in atherosclerosis research, as it is linked to cardiovascular risk and the effectiveness of various interventions.

Improving endothelial function through different cardiovascular risk-reducing strategies could serve as a potential surrogate marker for evaluating new treatments in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical implications of endothelial dysfunction. Widlansky, ME., Gokce, N., Keaney, JF., et al.[2023]

L-arginine supplementation (LAS) significantly improved exercise capacity and quality of life in heart transplant recipients after 6 weeks, as shown by increased walking distance and delayed ventilatory threshold during exercise tests.

LAS also enhanced the balance of nitric oxide to endothelin, which is important for endothelial function, indicating its potential as a beneficial treatment for improving exercise tolerance in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-arginine supplementation improves exercise capacity after a heart transplant. Doutreleau, S., Rouyer, O., Di Marco, P., et al.[2023]

Citations

1.

journals.plos.org

journals.plos.org/plosone/article?id=10.1371/journal.pone.0316798

Nutraceutical COMP-4 confers protection against endothelial ...

The PAI-1 results from this study suggest that COMP-4 may modulate tissue fibrosis and remodeling even after endothelial dysfunction has already occurred. This ...

2.

escholarship.org

escholarship.org/content/qt07g3100n/qt07g3100n.pdf

Nutraceutical COMP-4 confers protection ...

Co-incubation of COMP-4 with H2O2 reversed detrimental effects of H2O2 on endothelial function, evidenced by improvement in. NO availability and ...

3.

ucla.clinicaltrials.researcherprofiles.org

ucla.clinicaltrials.researcherprofiles.org/trial/NCT05595915

COMP-4 Supplementation and Brachial Artery FMD

The main goal of this study is to evaluate whether COMP-4, based on its ability to stimulate NO production by the endothelial cells, can improve FMD and ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC1434727/

Endothelial dysfunction: a comprehensive appraisal - PMC

Published data suggest that abnormal endothelial function precedes other evidence of vascular disease and that the progresion of metabolic syndrome to type 2 ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0891584925007580

Pharmacological targeting of endothelial nitric oxide ...

The review focuses on therapies targeting endothelial function and eNOS activity. Experimental and early-phase clinical strategies to restore eNOS function are ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05595915?tab=table

COMP-4 Supplementation and Brachial Artery FMD

The main goal of this study is to evaluate whether COMP-4, based on its ability to stimulate NO production by the endothelial cells, can improve FMD and ...

7.

withpower.com

withpower.com/trial/phase-2-aging-10-2022-2fa75

COMP-4 Supplementation for Endothelial Dysfunction

COMP-4 is a safe, clinically available, well tolerated oral supplement that has been shown in the lab to increase NO production in a number of differing tissues ...