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

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The principal goal for the study is to examine the role gut flora plays in modulating metabolism of dietary carnitine and choline in humans.

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 the treatment involving carnitine and choline generally safe for humans?

Research indicates that choline supplementation can affect carnitine levels in the body, but no adverse effects on serum lipids were observed, suggesting it may be safe. However, more studies are needed to fully understand the interactions and potential consequences of using choline and carnitine together. ^{1 2 3 4 5}

How does the treatment with Carnitine and Choline differ from other cardiovascular disease treatments?

This treatment is unique because it focuses on how gut bacteria metabolize Carnitine and Choline, which are nutrients found in red meat and other foods, to produce a compound called TMAO that is linked to heart disease. Unlike traditional treatments that directly target heart function or cholesterol levels, this approach explores modifying gut bacteria to potentially reduce cardiovascular risk. ^{1 3 6 7 8}

What data supports the effectiveness of the treatment involving antibiotics, carnitine, and choline for cardiovascular disease?

Research indicates that metabolites of phosphatidylcholine, such as choline and TMAO, are linked to increased cardiovascular risk. Suppressing gut bacteria in mice reduced atherosclerosis, suggesting that managing gut flora metabolism could be a potential approach for cardiovascular disease treatment. ^{1 3 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. England pubmed.ncbi.nlm.nih.gov

Plaque burden in HIV-infected patients is associated with serum intestinal microbiota-generated trimethylamine. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Quantification of choline in serum and plasma using a clinical nuclear magnetic resonance analyzer. [2021]

3. Slovakia pubmed.ncbi.nlm.nih.gov

Gut microorganisms and cardiovascular disease: carnitine is the answer. [2019]

4. Ireland pubmed.ncbi.nlm.nih.gov

Plasma levels of trimethylamine-N-oxide are confounded by impaired kidney function and poor metabolic control. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Choline and butyrate beneficially modulate the gut microbiome without affecting atherosclerosis in APOE*3-Leiden.CETP mice. [2022]

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

Choline supplementation reduces urinary carnitine excretion in humans. [2018]

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

Dietary patterns, food groups, and nutrients as predictors of plasma choline and betaine in middle-aged and elderly men and women. [2023]

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

Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. [2022]

10. England pubmed.ncbi.nlm.nih.gov

What connection is there between intestinal microbiota and heart disease? [2020]