Betaine for Heart Failure

Overseen By Timothy R Morgan, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Southern California Institute for Research and Education

Must be taking: Insulin sensitizers, Sulfonylureas

Must not be taking: Injectable insulin, Corticosteroids

Disqualifiers: Liver disease, Alcohol abuse, Heart failure, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests betaine, a food supplement, to determine its effectiveness for individuals with non-alcoholic fatty liver disease (NAFLD). The study evaluates betaine's impact on both diabetic and non-diabetic patients with insulin resistance. Participants will take betaine in powder form, mixed with a liquid, to assess liver health improvement over 12 weeks. This trial suits those diagnosed with NAFLD who also face issues related to diabetes or insulin resistance. As an unphased trial, it offers a unique opportunity to contribute to understanding betaine's potential benefits for liver health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use betaine or S-adenosylmethionine supplements during the study. If you are using injectable insulin or oral corticosteroids, you may not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that betaine is generally safe for use. It is a dietary supplement available without a prescription in the U.S. Studies have found no link between betaine use and a higher risk of heart problems in Japanese men and women. In fact, it might offer health benefits for those with heart conditions. For example, patients with heart issues like heart failure have used betaine and experienced positive effects.

Some studies have tested betaine at doses of 4 grams or 8 grams a day, similar to the amounts studied in clinical trials. These studies found that betaine is well-tolerated and does not cause major side effects. However, as with any supplement, individual reactions can vary. Consulting a healthcare provider before starting any new treatment is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about betaine for heart failure because it offers a novel approach by targeting metabolic pathways. Unlike traditional treatments such as ACE inhibitors, beta-blockers, or diuretics, which primarily manage symptoms or reduce fluid overload, betaine acts as a methyl donor, potentially improving cellular function and reducing liver fat. This mechanism may particularly benefit patients with non-alcoholic fatty liver disease (NAFLD) and heart failure, offering a dual-action potential that current heart failure medications do not address. By focusing on metabolic health, betaine could provide a more comprehensive treatment option for these patients.

What evidence suggests that betaine might be an effective treatment for heart failure?

Research has shown that betaine, also known as trimethylglycine, may support heart health and help with heart failure. Studies have found that it can lower levels of homocysteine in the blood, which is significant because high homocysteine levels are linked to heart diseases. Betaine also aids in producing glutathione, which maintains cell health and reduces stress on the heart. Some research suggests that higher blood levels of betaine might lower the risk of hospitalization for heart failure. Overall, betaine appears promising in supporting heart function and preventing heart-related issues.

In this trial, participants will be divided into two groups: diabetic patients with NAFLD and non-diabetics with NAFLD. Both groups will initially receive 4 grams of betaine per day. After 4 weeks, participants will be randomized to either continue with 4 grams or increase to 8 grams per day for an additional 8 weeks. ^{1 6 7 8 9}

Who Is on the Research Team?

Timothy R Morgan, MD

Principal Investigator

VA Long Beach Healthcare System

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with non-alcoholic fatty liver disease, elevated ALT levels (a liver enzyme), and normal platelet counts. They must not have severe liver or kidney issues. Group 1 specifically includes diabetic patients with high fasting blood sugar or HgA1c levels.

Inclusion Criteria

Alanine aminotransferase (ALT) levels ≥60 IU/mL

Platelets > 100,000/dL

Total bilirubin < 2 mg/dL

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 grams of betaine per day for the first 4 weeks, followed by randomization to either continue 4 grams or increase to 8 grams per day for an additional 8 weeks

12 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

2 visits (in-person) at 4 and 12 weeks post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Betaine (trimethyglycine)

Trial Overview The study tests two different doses of Betaine, a dietary supplement taken orally as a powder mixed in liquid. It aims to see if Betaine can improve liver health in people with fatty liver disease and type 2 diabetes.

How Is the Trial Designed?

Group I: diabetic patients with NAFLD Active Control 1 Intervention

Patients will be prescribed 4 grams of betaine/day (2 grams PO BID) for the first 4 weeks of the study. After 4 weeks, patients in each cohort will be randomized (1:1) to continue receiving betaine 4 grams per day or increase to 8 grams per day for an additional 8 weeks.

Group II: non-diabetics with NAFLD Active Control 1 Intervention

Patients will be prescribed 4 grams of betaine/day (2 grams PO BID) for the first 4 weeks of the study. After 4 weeks, patients in each cohort will be randomized (1:1) to continue receiving betaine 4 grams per day or increase to 8 grams per day for an additional 8 weeks.

Betaine (trimethyglycine) is already approved in European Union, United States for the following indications:

Approved in European Union as Betaine for:

• Homocystinuria

Approved in United States as Cystadane for:

• Homocystinuria

Who Is Running the Clinical Trial?

Southern California Institute for Research and Education

Lead Sponsor

Trials

27

Recruited

1,800+

Published Research Related to This Trial

In a study of 65 patients with chronic cardiac failure, treatment with trimethasidine MB significantly improved heart function and quality of life compared to the metabolic drug 3-TMHP, as evidenced by better results in stress echocardiography and increased left ventricular ejection fraction.

Trimethasidine MB demonstrated anti-ischemic effects by normalizing glucose metabolism in ischemic heart segments, making it a more effective option for patients with ischemic chronic heart failure than 3-TMHP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparative trial of efficacy of trimethasidine MB and 3-(2,2,2-trimethylhydrasine) propionate dihydrate in chronic heart failure]. Vasiuk, IuA., Iushchuk, EN., Shkol'nik, EL., et al.[2016]

In a study involving 45 patients with stable heart failure and reduced ejection fraction, trimetazidine (TMZ) did not lead to significant improvements in exercise capacity, left ventricular ejection fraction (LVEF), or quality of life after 6 months of treatment.

The addition of TMZ to standard medical therapy also showed no impact on mortality or cardiovascular events, suggesting it may not be beneficial for patients with advanced heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of trimetazidine in patients with severe chronic heart failure with reduced left ventricular ejection fraction: A prospective, randomized, open-label, cross-over study. Bohdan, M., Stopczyńska, I., Wiśniewski, P., et al.[2022]

A meta-analysis of 326 patients from 3 randomized controlled trials showed that trimetazidine (TMZ) significantly reduces all-cause mortality in patients with heart failure, with a relative risk of 0.283, indicating a strong protective effect.

TMZ, when added to standard heart failure treatment, not only improves cardiac parameters but also enhances event-free survival, suggesting it could be a valuable adjunct therapy for heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of trimetazidine added to pharmacological treatment on all-cause mortality in patients with systolic heart failure. Grajek, S., Michalak, M.[2015]

Trimetazidine significantly improved heart function in patients with heart failure, as shown by increased left ventricular ejection fraction and reduced left ventricular end-systolic volume across 17 trials involving 955 patients.

The treatment also demonstrated a protective effect against all-cause mortality and reduced hospitalizations and cardiovascular events, suggesting it could be a valuable addition to heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trimetazidine: a meta-analysis of randomised controlled trials in heart failure. Gao, D., Ning, N., Niu, X., et al.[2013]

In a study of 60 patients with stable nonischemic heart failure, trimetazidine (TMZ) did not significantly improve left ventricular ejection fraction (LVEF) or overall exercise capacity after 6 months of treatment.

While TMZ was added to optimal medical therapy, it showed no meaningful changes in quality of life or cardiac metabolism, indicating that it may not provide additional benefits for patients with nonischemic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of trimetazidine in nonischemic heart failure: a randomized study. Winter, JL., Castro, PF., Quintana, JC., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4262445/

Betaine and Trimethylamine-N-Oxide as Predictors of ... 3), and suggest that for the outcome of hospitalization for heart failure, high plasma betaine may be predictive. ... cardiovascular disease: a ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0022316622161778

Low Dose Betaine Supplementation Leads to Immediate ... As new evidence continues to confirm that plasma homocysteine is a cause of cardiovascular disease, a diet rich in betaine might prove effective in lowering ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03073343

NCT03073343 | A Prospective, Randomized, Open Label ... Participation Criteria · Age 18-75 years · A clinical diagnosis of non-alcoholic fatty liver disease. · Alanine aminotransferase (ALT) levels ≥60 IU/mL · Laboratory ...

4. academic.oup.com academic.oup.com/jcem/article/103/8/3038/5025795

Metabolic Effects of Betaine: A Randomized Clinical Trial of ... ... heart failure in patients with established disease (5–7). Betaine has three key physiologic functions: It acts as a substrate for glutathione synthesis and ...

5. eureka.patsnap.com eureka.patsnap.com/report-benchmarking-trimethylglycine-for-cardiovascular-health-improvements

Benchmarking Trimethylglycine for Cardiovascular Health ... TMG for cardiovascular disease prevention: Trimethylglycine (TMG) has been shown to be effective in preventing cardiovascular diseases by ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03073343

NCT03073343 | A Prospective, Randomized, Open Label ... Known heart failure of New York Heart Association class 2, 3, or 4; Any condition, which in the opinion of the investigator, would impede compliance or ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0022316624010186

Decoding Betaine: A Critical Analysis of Therapeutic ... Tsuji, et al. Choline and betaine intakes are not associated with cardiovascular disease mortality risk in Japanese men and women. J. Nutr., 145 (2015), pp ...

8. mdpi.com mdpi.com/2076-3921/14/7/771

Betaine Dietary Supplementation: Healthy Aspects in ... In patients with cardiovascular conditions such as cardiac decompensation and congestive heart failure, betaine supplementation has been associated with ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6692715/

Metabolic Effects of Betaine: A Randomized Clinical Trial ... ... risk for myocardial infarction and heart failure in patients with established disease (5–7). Betaine has three key physiologic functions: It acts as a ...