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

50 Participants Needed

Trial Summary

What is the purpose of this trial?

In a young and 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 promote 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 even coronary artery disease later on in life in these patients. Therefore, the ability to somehow 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. 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 including human vascular endothelial cells. In this proposed human study, the investigators plan on recruiting healthy, young participants willing to take COMP-4 for a 14 day period in whom the investigators will measure in a non-invasive way - by the use of ultrasound - the effect of COMP-4 on its ability to improve blood flow in one of the major blood vessels of the upper arm. In addition, the investigators will also determine whether COMP-4 will be capable of lowering in the blood the levels of two of the most studied inflammatory markers associated with endothelial dysfunction, IL-8 and PAI-1.

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.

What data supports the effectiveness of the treatment COMP-4 for endothelial dysfunction?

Research suggests that chronic antioxidant use can improve endothelial function by enhancing blood vessel dilation and reducing harmful cell interactions. Additionally, L-arginine, a component that may be similar to those in COMP-4, has been shown to improve endothelial function and lower blood pressure in certain individuals. ^{1 2 3 4 5}

How is the treatment COMP-4 different from other treatments for endothelial dysfunction?

COMP-4 is unique because it likely includes L-arginine, which helps improve endothelial function by increasing nitric oxide production, a key factor in blood vessel health. This approach is different from other treatments as it directly targets the underlying cause of endothelial dysfunction by enhancing nitric oxide availability. ^{1 5 6 7 8}

Research Team

Sriram V. Eleswarapu, MD PhD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

L-Arginine and vascular health. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical implications of endothelial dysfunction. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

The clinical implications of endothelial dysfunction. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Chronic antioxidant use and changes in endothelial dysfunction: a review of clinical investigations. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

L-arginine supplementation improves exercise capacity after a heart transplant. [2023]

6. Chile pubmed.ncbi.nlm.nih.gov

[Modification of phenylephrine induced contraction of human vessel rings by L-arginine and L-arginine methyl ester]. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

L-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation. [2018]