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

Trial Summary

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.

How is the drug Betaine different from other heart failure treatments?

Betaine (trimethyglycine) is unique for heart failure treatment as it is not commonly used for this condition, unlike trimetazidine, which is known for its antioxidant properties and ability to improve cardiac metabolism. Betaine's potential benefits in heart failure may relate to its role in cellular metabolism and methylation processes, which are different from the mechanisms of standard heart failure drugs. ^{1 2 3 4 5}

What is the purpose of this trial?

Betaine (trimethyglycine) is a food supplement that is approved for sale in the United States without a prescription. In this study, betaine will be provided to patients as a powder that can be mixed with aqueous solutions and consumed orally.

Research Team

Timothy R Morgan, MD

Principal Investigator

VA Long Beach Healthcare System

Eligibility Criteria

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

I have been diagnosed with non-alcoholic fatty liver disease.

Alanine aminotransferase (ALT) levels ≥60 IU/mL

Platelets > 100,000/dL

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Trimetazidine: a meta-analysis of randomised controlled trials in heart failure. [2013]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Comparative trial of efficacy of trimethasidine MB and 3-(2,2,2-trimethylhydrasine) propionate dihydrate in chronic heart failure]. [2016]

3. Poland 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. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Effects of trimetazidine in nonischemic heart failure: a randomized study. [2016]