Taurine Supplementation for Cardiomyopathy in Thalassemia

(TICATS Trial)

Overseen By Red blood Cell Disorders Clinical Trials Program

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must be taking: Iron chelation

Must not be taking: Investigational products

Disqualifiers: Heart failure, Pregnancy, others

Compensation: Varies

Number of Visits: 3

Duration: 12 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Hypothesis: Taurine, in combination with standard iron chelation therapy, is more effective than chelation therapy alone in reducing cardiac iron overload, oxidative stress and cardiac damage in β-Thalassemia. Protocol: Sixty subjects with transfusion dependent β-Thalassemia receiving deferasirox iron chelation therapy will be recruited and randomized in a 1:1 ratio to either (1) placebo and continuation of their iron chelation or (2) a combination of iron chelation plus taurine. Transfusion and safety visits will be scheduled monthly with clinical/biochemical assessment visits every three months. The efficacy of taurine combined with standard chelation therapy will be assessed at baseline and 12 months posttreatment by both cardiac T2\*MRI, and cardiac function. The recruitment period is projected to be 12 months from initiation.

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 must be on a stable dose of iron chelation therapy for more than 30 days to participate.

What data supports the effectiveness of taurine supplementation for cardiomyopathy in thalassemia?

Research in animals suggests that taurine might help reduce heart damage caused by iron overload, which is a problem in thalassemia patients. This is because taurine may prevent damage from oxidative stress (harmful chemical reactions) and reduce iron uptake in the heart. ^{1 2 3 4 5}

Is taurine supplementation safe for humans?

Research suggests that taurine may help prevent heart damage related to iron overload, but specific safety data for taurine supplementation in humans is not provided in the available studies. ^{1 4 5 6 7}

How does the placebo treatment differ from other treatments for cardiomyopathy in thalassemia?

The placebo treatment is a 'dummy' treatment used as a control in clinical trials to compare the effects of the actual treatment, in this case, taurine supplementation, which is being studied for its potential benefits in heart conditions like cardiomyopathy. Unlike active treatments, the placebo does not contain any therapeutic ingredients and is used to help researchers determine the true effectiveness of the treatment being tested. ^{8 9 10 11 12}

Eligibility Criteria

This trial is for adults over 18 with transfusion-dependent Thalassemia, a specific heart condition (LVEF >50%), and certain levels of iron in the heart and liver. It's not for those with recent other trials, high liver iron, low serum ferritin, frequent transfusions or potential pregnancy.

Inclusion Criteria

I have been on a consistent iron removal treatment for over a month.

I have transfusion-dependent Thalassemia and am being treated at the RBC clinic at TGH.

My heart MRI result is normal and was done within the last 3 months.

Exclusion Criteria

My liver iron concentration is high, as confirmed by a recent MRI.

As a result of medical review, physical examination or screening investigations, the investigator considers the subject unfit for the study

No fixed address

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either placebo or taurine in combination with standard iron chelation therapy

12 months

Monthly transfusion and safety visits, clinical/biochemical assessment every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Taurine

Trial Overview The study tests if Taurine added to standard iron removal treatment works better than the treatment alone in reducing heart damage from too much iron in patients with β-Thalassemia. Participants are randomly assigned to get either Taurine or a placebo alongside their usual therapy.

Participant Groups

Group I: Taurine Experimental Treatment 1 Intervention

675mg taurine four times daily

Group II: Placebo Placebo Group 1 Intervention

placebo four times daily

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

Thalassemias have significantly increased the global burden of heart failure (HF) since 1990, with the highest number of cases reported in China and the highest prevalence in Pakistan, indicating a growing health concern.

The study highlights that males are more affected by HF related to thalassemias than females, and while middle sociodemographic index regions show improvement, low SDI regions are becoming hotspots for these conditions, suggesting a need for targeted health policies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing trends in the prevalence of heart failure impairment with Thalassemias over three decades. Tang, H., Zhang, N., Deng, J., et al.[2023]

In a crossover study involving 19 patients with transfusion-dependent β-thalassemia, amlodipine treatment significantly improved myocardial iron loading status, as indicated by an increase in myocardial MRI T2* values from 9.83 ms to 11.44 ms.

Amlodipine also led to a reduction in serum ferritin levels, suggesting its potential efficacy in managing iron overload in these patients, although further research with larger sample sizes is necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, controlled, crossover trial of amlodipine on iron overload status in transfusion dependent β-thalassemia patients. Karami, H., Khalilzadeh Arjmandi, H., Salehifar, E., et al.[2021]

In a 5-year study of 52 patients with beta thalassemia and heart failure, 48% survived, indicating a better survival rate than previously reported for this condition.

Patients with left-sided heart failure were generally younger and had lower heart function (ejection fraction) and lower serum ferritin levels compared to those with right-sided heart failure, suggesting distinct clinical profiles that could influence treatment and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart failure in beta thalassemia: a 5-year follow-up study. Kremastinos, DT., Tsetsos, GA., Tsiapras, DP., et al.[2022]

In a study of 40 β-Thalassemia major patients aged 6 to 20, adding amlodipine to standard iron chelation therapy significantly reduced myocardial iron concentration after 6 months, indicating improved heart health.

Amlodipine also increased myocardial T2* values, suggesting enhanced cardiac function, without causing additional adverse effects compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major. Khaled, A., Salem, HA., Ezzat, DA., et al.[2022]

Taurine supplementation in a murine model of iron cardiomyopathy did not significantly reduce cardiac iron levels but did improve liver glutathione peroxidase activity, suggesting its role as an antioxidant rather than an iron uptake inhibitor.

Iron overload led to increased oxidative stress markers in the heart, while taurine helped ameliorate some of these oxidative changes, indicating potential protective effects against iron-induced damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antioxidant-mediated effects in a gerbil model of iron overload. Otto-Duessel, M., Aguilar, M., Moats, R., et al.[2021]

In a review of 15 randomized controlled trials involving 1003 β-Thalassemia major patients, deferiprone (DFP) was found to be more effective than deferoxamine (DFO) in improving cardiac ejection fraction and reducing endocrine dysfunction.

Combination therapy of DFP and DFO showed even greater efficacy in improving cardiac ejection fraction compared to either drug alone, but overall evidence quality was low, indicating a need for larger studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of deferiprone monotherapy and in combination with deferoxamine for reduction of iron overload in chronically transfused patients with β-thalassemia. Kuo, KH., Mrkobrada, M.[2018]

In a study of 56 patients with thalassemia major, adding amlodipine to iron chelation therapy significantly improved myocardial iron levels after 12 months, indicating enhanced efficacy in reducing iron overload.

The combination therapy was found to be safe, with only mild gastrointestinal upset reported as a side effect, and it did not significantly affect liver iron levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, controlled study evaluating effects of amlodipine addition to chelators to reduce iron loading in patients with thalassemia major. Eghbali, A., Kazemi, H., Taherahmadi, H., et al.[2022]

In a study on rats, taurine supplementation was found to significantly protect the heart from damage caused by exhaustive exercise by inhibiting changes in thyroid hormone metabolism and second messenger activity.

After exhaustive swimming, taurine helped maintain normal levels of triiodothyronine (T3) and prevented increases in T(4) 5' deiodinase activity and cAMP levels, suggesting it plays a protective role against exercise-induced myocardial stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of taurine on thyroid hormone and second messenger in myocardium of rats after exhaustive exercise]. Zhang, J., Huang, SH., Chen, BM.[2013]

Long-term taurine treatment (1 g/kg/day for 6 months) significantly improved heart function in mdx mice, a model for Duchenne muscular dystrophy, by counteracting the decline in left ventricular function parameters.

Taurine treatment reduced histological damage and inflammation in the heart, but did not show effects on skeletal muscle function, indicating its specific benefits for cardiac health in later stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A long-term treatment with taurine prevents cardiac dysfunction in mdx mice. Mele, A., Mantuano, P., De Bellis, M., et al.[2019]

A study involving 85 boys with Duchenne muscular dystrophy (DMD) found that a combination of heart medications, perindopril and bisoprolol, was well tolerated over 36 months, with no significant adverse effects reported.

However, the combination therapy did not show a significant benefit in preventing or delaying the decline in left ventricular ejection fraction (LVEF) compared to placebo, indicating that it may not be effective in altering the progression of cardiomyopathy in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing Cardiomyopathy in DMD: A Randomized Placebo-Controlled Drug Trial. Bourke, JP., Watson, G., Spinty, S., et al.[2022]

In a study using the mdx mouse model for Duchenne muscular dystrophy (DMD), both taurine and the cysteine precursor OTC increased taurine levels in muscle and improved muscle function, but taurine was found to be more effective overall.

While OTC treatment showed some benefits, it also led to weight loss in the mice, indicating potential adverse effects, which suggests that increasing dietary taurine may be a safer and more effective therapeutic approach for DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy. Terrill, JR., Pinniger, GJ., Graves, JA., et al.[2022]

Taurine supplementation, while safe and inexpensive, has not yet been proven effective for treating dilated cardiomyopathy (DCM) in humans, as current studies primarily involve patients with all-cause heart failure rather than specifically DCM.

Out of 285 articles reviewed, only 11 met the inclusion criteria, and while some studies reported improvements in heart function and exercise capacity, the meta-analysis did not find significant benefits in ejection fraction or stroke volume, indicating the need for more targeted clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of taurine administration on symptoms, severity, or clinical outcome of dilated cardiomyopathy and heart failure in humans: a systematic review. McGurk, KA., Kasapi, M., Ware, JS.[2023]

References

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

Changing trends in the prevalence of heart failure impairment with Thalassemias over three decades. [2023]

2. India pubmed.ncbi.nlm.nih.gov

A double-blind, controlled, crossover trial of amlodipine on iron overload status in transfusion dependent β-thalassemia patients. [2021]

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

Heart failure in beta thalassemia: a 5-year follow-up study. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Antioxidant-mediated effects in a gerbil model of iron overload. [2021]

6. England pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of deferiprone monotherapy and in combination with deferoxamine for reduction of iron overload in chronically transfused patients with β-thalassemia. [2018]

7. England pubmed.ncbi.nlm.nih.gov

A randomized, controlled study evaluating effects of amlodipine addition to chelators to reduce iron loading in patients with thalassemia major. [2022]

8. China pubmed.ncbi.nlm.nih.gov

[Effect of taurine on thyroid hormone and second messenger in myocardium of rats after exhaustive exercise]. [2013]

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

A long-term treatment with taurine prevents cardiac dysfunction in mdx mice. [2019]

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

Preventing Cardiomyopathy in DMD: A Randomized Placebo-Controlled Drug Trial. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Effect of taurine administration on symptoms, severity, or clinical outcome of dilated cardiomyopathy and heart failure in humans: a systematic review. [2023]