Carnitine Supplementation for Arterial Stiffness

Overseen By Sandra Pena, CCRP

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Baylor College of Medicine

Disqualifiers: Seizure disorder, Renal failure, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a protein supplement called carnitine might affect arterial stiffness, the hardening of blood vessels. Since arterial stiffness can lead to heart disease, preventing or treating it could be crucial for future health. Researchers will randomly assign participants either carnitine or a placebo to compare their effects. The trial seeks adolescents with specific cholesterol levels: triglyceride levels above 130 mg/dL but less than 500 mg/dL, and LDL cholesterol under 160 mg/dL. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a known metabolic disorder that requires carnitine therapy, you cannot participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that carnitine supplements are usually safe for use. Some studies have examined carnitine's effects on heart health, suggesting it might aid in energy production and reduce heart stress. However, evidence on carnitine's impact on blood vessel stiffness remains mixed.

Certain research has found that carnitine might alter artery stiffness, potentially influencing heart health, though the exact effects are still under investigation. Overall, carnitine has been used for various health purposes, with no major safety issues reported in available studies.

In this trial, participants will take carnitine in liquid form. It is important for potential participants to know that the safety of this treatment in humans is still under study. However, past studies offer some reassurance about its general safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for arterial stiffness?

Unlike many treatments for arterial stiffness that focus on controlling blood pressure or cholesterol, carnitine supplementation offers a unique approach by potentially improving the flexibility of blood vessels directly. Carnitine is a naturally occurring compound that plays a vital role in energy production, and researchers believe it might enhance arterial health by boosting mitochondrial function and reducing oxidative stress. This could make carnitine a promising option for patients seeking a novel and potentially more direct method to address arterial stiffness.

What evidence suggests that carnitine supplementation could be effective for arterial stiffness?

This trial will compare carnitine supplementation (CS+) with a placebo (CS-) to assess its effects on arterial stiffness. Research has shown that carnitine, a protein supplement, might be important for heart health. It helps the body make energy, reduces damage from harmful molecules, and maintains healthy blood vessels. While direct evidence on its effect on artery stiffness is lacking, carnitine has shown promise in related areas like improving heart health and managing cholesterol. Some studies suggest that carnitine might help with insulin resistance and fat issues, which are linked to artery problems. Overall, carnitine's potential to support heart health makes it a promising candidate for further study on artery stiffness. ^{2 6 7 8 9}

Who Is on the Research Team?

Justin P Zachariah, MD MPH

Principal Investigator

Study Principal Investigator

Are You a Good Fit for This Trial?

This trial is for boys and girls aged 11-21 with high triglyceride levels, but not too high cholesterol or any severe health issues like kidney failure, diabetes, heart disease, seizures, or pregnancy. They should be willing to follow the study rules.

Inclusion Criteria

My fasting triglyceride levels are between 130 and 500 mg/dL.

I am between 13 and 19 years old.

I am between 11 and 21 years old.

Exclusion Criteria

I have a heart condition from birth that needed surgery or a catheter procedure.

Nonadherence to study protocol during run-in phase defined as possessing 25% more than the expected remainder of placebo supplement pro-rated to the day of assessment

I need carnitine therapy for my metabolic disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 months of oral carnitine supplementation or placebo to study its effects on arterial stiffness

6 months

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CS-
• CS+

Trial Overview

The study tests if a protein supplement called carnitine can prevent hardening of blood vessels in at-risk teens. Participants are randomly chosen to receive carnitine or not and researchers will also look at their genes related to carnitine.

How Is the Trial Designed?

Group I: Carnitine supplementation (CS+) Experimental Treatment 1 Intervention

Carnitine supplementation in liquid form, sugar free.

Group II: Placebo (CS-) Placebo Group 1 Intervention

Placebo comparator liquid similar in appearance and taste to CS+.

CS- is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as L-Carnitine for:

• Dietary supplement for heart health and energy production

Approved in European Union as Levocarnitine for:

• Treatment of carnitine deficiency, adjunctive therapy for the treatment of angina pectoris

Approved in Canada as L-Carnitine for:

• Dietary supplement for heart health and energy production

Approved in Japan as Levocarnitine for:

• Treatment of carnitine deficiency

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

L-carnitine (LC) and taurine (TAU) work together to significantly inhibit the growth and osteoblastic differentiation of vascular smooth muscle cells (VSMCs), as shown by reduced DNA synthesis and alkaline phosphatase activity in laboratory tests.

The effectiveness of this combination is linked to LC enhancing the uptake of TAU and increasing the expression of the TAU transporter, indicating a specific mechanism of action that could be targeted for therapeutic purposes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-carnitine and taurine synergistically inhibit the proliferation and osteoblastic differentiation of vascular smooth muscle cells. Xie, H., Yang, B., Zhou, XM., et al.[2021]

In a study of 120 patients aged 54-67 with cardiovascular issues and moderate cognitive deficits, the addition of levocarnitine and acetylcarnitine to standard treatment significantly reduced cognitive deficits over a follow-up period of 70 days.

The treatment was well-tolerated and safe, suggesting that these compounds may help improve cognitive function by correcting endothelial dysfunction in patients with cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Possibilities of sequential levocarnitin and acetylcarnitin treatment in correcting cognitive deficiency in patients with cardiovascular diseases]. Statsenko, ME., Turkina, SV.[2021]

L-carnitine supplementation (1000 mg/d) for 12 weeks significantly reduced inflammation markers in patients with coronary artery disease (CAD), including C-reactive protein (CRP) and interleukin-6 (IL-6), compared to baseline and placebo groups.

The study involved 47 patients with CAD, and the results suggest that L-carnitine may help lower inflammation due to its antioxidant properties, indicating potential benefits for managing CAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiinflammatory effects of L-carnitine supplementation (1000 mg/d) in coronary artery disease patients. Lee, BJ., Lin, JS., Lin, YC., et al.[2022]

L-propionyl-carnitine (LPC) significantly improved arteriolar function during reperfusion in patients with intermittent claudication, as indicated by increased laser-Doppler power spectrum measurements after LPC infusion.

LPC also reduced tissue acidosis during ischaemia and reperfusion, suggesting it protects tissues from ischaemic injury without affecting overall blood flow, indicating its potential for broader use in peripheral arterial disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-propionyl-carnitine protects tissues from ischaemic injury in an 'in vivo' human ischaemia-reperfusion model. Andreozzi, GM., Martini, R., Cordova, RM., et al.[2021]

In a study involving 22 patients with peripheral arterial disease, L-carnitine supplementation significantly improved walking capacity in patients with low resting levels of acetylcarnitine, indicating its potential efficacy in enhancing exercise performance.

The results suggest that measuring plasma acetylcarnitine levels can help identify which patients are most likely to benefit from L-carnitine therapy, as those with elevated resting levels did not show improvement after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carnitine-related alterations in patients with intermittent claudication: indication for a focused carnitine therapy. Brevetti, G., di Lisa, F., Perna, S., et al.[2019]

In a randomized, double-blind, placebo-controlled trial involving 36 hemodialysis patients, l-carnitine supplementation significantly increased serum free carnitine levels by 150% and reduced serum amyloid A (SAA) by 32%, indicating its potential to lower systemic inflammation.

While l-carnitine effectively decreased SAA, a marker associated with cardiovascular risk, it did not significantly affect other vascular inflammation markers, suggesting a targeted mechanism of action in reducing inflammation specifically related to SAA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of l-carnitine supplement on serum amyloid A and vascular inflammation markers in hemodialysis patients: a randomized controlled trial. Tabibi, H., Hakeshzadeh, F., Hedayati, M., et al.[2015]

In a 12-week study involving seven patients with peripheral arterial disease, supplementation with propionyl-L-carnitine (PLC) at 2 g per day showed a modest improvement in walking performance for some individuals, despite no significant increase in the overall group.

Muscle strength significantly increased from 695 N to 812 N after 4 weeks of PLC supplementation, indicating that PLC may enhance muscle strength in patients with peripheral arterial disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of propionyl-L-carnitine on exercise performance in peripheral arterial disease. Barker, GA., Green, S., Askew, CD., et al.[2019]

In a study of 65 kidney transplant patients, lower serum levels of l-carnitine were significantly associated with higher rates of peripheral arterial stiffness (PAS), indicating that l-carnitine may play a protective role in vascular health post-transplant.

The research found that l-carnitine levels can independently predict PAS, with a diagnostic power of 0.789, suggesting that monitoring l-carnitine could be important for managing cardiovascular risks in kidney transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Low Serum l-Carnitine Levels with Peripheral Arterial Stiffness in Patients Who Undergo Kidney Transplantation. Lai, YH., Lee, MC., Ho, GJ., et al.[2020]

Treatment with L-carnitine (LC) and propionyl-L-carnitine (PLC) improved endothelial function in small mesenteric arteries of spontaneously hypertensive rats without affecting blood pressure, indicating their potential as therapeutic agents for endothelial dysfunction.

Propionyl-L-carnitine specifically increased the expression of eNOS, enhancing nitric oxide availability, which is crucial for vascular relaxation, while both treatments reduced harmful superoxide production in hypertensive rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of L-carnitine and propionyl-L-carnitine on endothelial function of small mesenteric arteries from SHR. Alvarez de Sotomayor, M., Bueno, R., Pérez-Guerrero, C., et al.[2022]

A study involving 166 adolescents with dyslipidemia evaluated the effects of 6 months of 3 g daily oral l-carnitine supplementation on arterial stiffness and lipid levels, aiming to understand its potential role in preventing hypertension.

The research is designed to explore both genetic and supplemental influences of carnitine on cardiovascular health, which could lead to new therapies for young individuals at risk of atherosclerotic cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exogenous l-carnitine on aortic stiffness in dyslipidemic adolescents: Design of a quadruple-blind, randomized, controlled interventional trial. Zachariah, JP., Pena, S., Lupo, PJ., et al.[2023]

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Conflicting observational and Mendelian randomization data suggest endogenous carnitine may affect arterial stiffness and lipid traits. Because of this, we ...

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L-carnitine seems to have a pivotal role in cardiovascular health due to its energy metabolism, anti-oxidative stress, and endothelial role.

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clinicaltrials.gov/study/NCT04128969

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The study will also investigate the role of carnitine in insulin resistance and dyslipidemia at this same age, which may serve as grounds for future therapeutic ...

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This study evaluated the relationship between serum l-carnitine level and peripheral arterial stiffness (PAS) in kidney transplantation (KT).

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Effect of exogenous l-carnitine on aortic stiffness in ...

Therefore observational and trial data show relations between carnitine and arterial stiffness. Our published 2 sample Mendelian randomization analysis showed ...

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In both aged adults and coronary artery disease patients acylcarnitines, carnitine derivatives, are associated with large artery stiffness [33,34].

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Risk assessment for carnitine

Conflicting observational and Mendelian randomization data suggest endogenous carnitine may affect arterial stiffness and lipid traits.