Gut Flora Metabolism of Carnitine and Choline for Cardiovascular Disease

(CARNIVAL Trial)

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: The Cleveland Clinic

Must not be taking: Antibiotics, Probiotics

Disqualifiers: Heart failure, Renal failure, Pulmonary disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how gut bacteria affect the processing of carnitine and choline—nutrients found in foods like meat and eggs—and their impact on heart health. Participants will receive supplements of carnitine or choline, sometimes combined with aspirin or antibiotics, to observe how these combinations influence gut bacteria and overall heart function. Suitable candidates have not recently taken antibiotics or probiotics, do not have serious chronic illnesses, and have not undergone certain types of stomach surgery. As an Early Phase 1 trial, this research aims to understand how these treatments work in people, offering participants the chance to gain new insights into heart health.

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 significant chronic illness or are taking antibiotics, you may not be eligible to participate.

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

Research has shown that carnitine is usually safe, but its impact on heart health remains unclear. Some studies suggest it might protect the heart, while others indicate potential harm, resulting in mixed outcomes.

For choline, findings are similarly varied. Certain research suggests that increased choline intake might reduce the risk of specific heart issues. However, other studies associate it with a higher risk of heart problems and even increased mortality.

Antibiotics like ciprofloxacin and vancomycin raise concerns, as they may increase the risk of heart-related issues, such as heart attacks or irregular heartbeats, particularly in older adults or those with existing heart conditions.

Overall, these treatments present a mixed safety profile, so it is important to consider these factors when deciding about joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore how gut flora interacts with carnitine and choline to impact cardiovascular health. Unlike standard treatments that typically focus on lowering cholesterol or blood pressure, these supplements target gut metabolism. Carnitine and choline could influence heart health by modifying gut bacteria activity, potentially offering a new angle for cardiovascular disease management. This fresh focus on the gut-heart connection might open doors to innovative therapies that complement existing options like statins or beta-blockers.

What evidence suggests that this trial's treatments could be effective for cardiovascular disease?

In this trial, participants will join different treatment arms to evaluate the effects of L-carnitine, choline, and antibiotics on cardiovascular health. Previous studies have shown that L-carnitine can lower risks associated with heart diseases, with a 27% reduction in overall death rates and noticeable improvements in heart-related symptoms. For choline, findings are mixed. Some research suggests it may benefit heart health by lowering blood pressure and improving cholesterol levels, while other studies indicate a possible increased risk of heart problems with higher intake. Regarding antibiotics, evidence does not strongly support their use in preventing heart disease, as they have not significantly reduced heart-related events. ^{6 7 8 9 10}

Who Is on the Research Team?

Stanley L. Hazen, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

The CARNIVAL Study is for men and women aged 18 or older who can follow the study's rules. It's not for those with recent infections, antibiotic use within 2 months, chronic gut issues, intolerance to probiotics, serious illnesses like heart failure or pregnancy, past stomach surgeries, or recent use of probiotics including yogurt.

Inclusion Criteria

Able to provide informed consent and comply with study protocol

Exclusion Criteria

I have long-term stomach or bowel problems or can't tolerate probiotics.

I do not have serious long-term illnesses like heart or kidney failure.

I have taken OTC probiotics or eaten yogurt recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dietary supplements (carnitine or choline) and aspirin or antibiotics as per assigned group

2 months

Regular visits for monitoring and supplement administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Antibiotics
• Carnitine
• Carnitine and Aspirin
• Choline
• Choline and Aspirin

Trial Overview This study looks at how gut bacteria affect the body's processing of carnitine and choline from food. Participants will receive different combinations of carnitine, choline, antibiotics, and aspirin to see how these influence cardiovascular health.

How Is the Trial Designed?

Group I: Carnitine and Aspirin Active Control 1 Intervention

Carnitine supplement 500 mg capsule by mouth, twice daily for 2 months Drug: aspirin 81 mg by mouth, daily for 3 months (on aspirin for 1 month prior to starting study and 2 months with Carnitine supplementation during study) Other Names: Ecotrin, Bufferin, Ascriptin, Fasprin, Norwich Aspirin, Durlaza, Bayer Genuine Aspirin, Genacote, Bayer, Halfprin, Aspirtab, Aspir Low, Aspir-Trin

Group II: Antibiotics Active Control 1 Intervention

Antibiotics (Ciprofloxacin, Vancomycin, Metronidazole and Neomycin) Drug: Ciprofloxacin 500 mg, po, twice daily for 7 days (Other Names: Cipro) Drug: Metronidazole 500 mg, po, twice daily for 7 days (Other Names: Flagyl, Noritate, Rosadan, Vandazole, Flagyl ER, Vitazol) Drug: Vancomycin 125 mg, po, 4 times daily for 7 days (Other Names: Vancocin, Vancocin HCl, Pulvules, Vancoled, Novaplus, PremierPro Rx, Vancomycin HCl) Drug: Neomycin 1 gram, po, four times daily for 7 days (Other Names: Aminoglycoside)

Group III: Choline and Aspirin Active Control 1 Intervention

Choline supplement 500 mg capsule by mouth, twice daily for 2 months Drug: aspirin 81 mg by mouth, daily for 3 months (on aspirin for 1 month prior to starting study and 2 months with Choline supplementation during study) Other Names: Ecotrin, Bufferin, Ascriptin, Fasprin, Norwich Aspirin, Durlaza, Bayer Genuine Aspirin, Genacote, Bayer, Halfprin, Aspirtab, Aspir Low, Aspir-Trin

Group IV: Carnitine (No antibiotics, No aspirin) Active Control 1 Intervention

L-Carnitine 500 mg capsule by mouth, twice daily for 2 months. No aspirin for 1 month prior to starting study and remains off aspirin during study.

Group V: Choline (No Antibiotics, No aspirin) Active Control 1 Intervention

Choline 500 mg capsule by mouth, twice daily for 2 months. No aspirin for 1 month prior to starting study and remains off aspirin during study.

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6483534/

Antibiotics for secondary prevention of coronary heart disease The first trials that investigated the use of antibiotics for secondary prevention of coronary heart disease were published in the late 1990s. The trials ...

2. ahajournals.org ahajournals.org/doi/10.1161/JAHA.122.028939

Relationship Between Azithromycin and Cardiovascular ... Azithromycin use in patients with COVID‐19 and prior history of CVD is significantly associated with an increased risk of AHF and all‐cause 30‐day mortality.

3. medrxiv.org medrxiv.org/content/10.1101/2025.09.24.25336595v1.full.pdf

Trends in Antibiotic Use among Cardiovascular Heart ... Conclusions: Antibiotic use among cardiovascular inpatients at JKCI is high, with heavy reliance on broad-spectrum and Reserve agents.

4. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003610.pub4/full?HootPostID=5be11d6b-f548-41c2-b0e6-10f46aa1d7f2&Socialprofile=wiley%20health&Socialnetwork=facebook

Antibiotics for secondary prevention of coronary heart ... Antibiotics might help patients with coronary heart disease and reduce their risk of heart attacks, strokes, chest pain, revascularisation ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0021915004005714

Antibiotics for vascular diseases: a meta-analysis of ... Conclusions: Overall, antibiotic treatment did not significantly reduce occurrence of new vascular events or death. However, further trials are needed to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7550792/

A self‐controlled case series analysis Fluoroquinolones were associated with an increased risk of all‐cause mortality vs multiple antibiotics commonly used for outpatient infections.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6169761/

Association of oral ciprofloxacin, levofloxacin, ofloxacin and ... The risk of ventricular arrhythmia was especially high in moxifloxacin users who were older or had cardiovascular disease. For 8–14 days after ...

8. ahajournals.org ahajournals.org/doi/10.1161/JAHA.117.008074

Estimated Cardiac Risk Associated With Macrolides and ... Macrolides and fluoroquinolones were associated with a risk of cardiac events. However, the risk associated with macrolide use was substantially attenuated.

9. sph.tulane.edu sph.tulane.edu/antibiotic-use-linked-greater-risk-heart-attack-and-stroke

Antibiotic Use Linked to Greater Risk of Heart Attack and Stroke Researchers found that women aged 60 or older who took antibiotics for two months or more had the greatest risk of cardiovascular disease, but long duration of ...

10. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-warns-about-increased-risk-ruptures-or-tears-aorta-blood-vessel-fluoroquinolone-antibiotics

FDA warns about increased risk of ruptures or tears in the ... Fluoroquinolone antibiotics can increase the occurrence of rare but serious events of ruptures or tears in the main artery of the body, called ...