Sotagliflozin for Hypertrophic Cardiomyopathy

(SOTA-CROSS HCM Trial)

Overseen By Sharlene Day, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Must not be taking: SGLT2 inhibitors

Disqualifiers: Type 1 diabetes, Uncontrolled Afib, Severe lung disease, others

Compensation: Varies

Number of Visits: 8

26 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants have stable medical therapy for at least 1 month before joining, but it does not specify if you need to stop any current medications. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Sotagliflozin for treating Hypertrophic Cardiomyopathy?

Sotagliflozin, a drug that helps manage blood sugar, has shown benefits in heart failure patients with diabetes by reducing heart-related events and hospitalizations. While it hasn't been specifically tested for Hypertrophic Cardiomyopathy, its positive effects on heart health in similar conditions suggest it might be helpful. ^{1 2 3 4 5}

Is sotagliflozin safe for humans?

Sotagliflozin has been studied for safety in people with diabetes and heart failure. It generally shows acceptable safety, with no increased risk for serious conditions like diabetic ketoacidosis or urinary tract infections, though it may cause mild diarrhea. ^{2 4 6 7 8}

How does the drug sotagliflozin differ from other treatments for hypertrophic cardiomyopathy?

Sotagliflozin is unique because it is a dual inhibitor of sodium-glucose co-transporters (SGLT) 1 and 2, which is different from other treatments that typically target only SGLT2. This dual action may offer additional cardiovascular benefits, such as reducing heart failure events and improving heart function, which are not typically addressed by standard treatments for hypertrophic cardiomyopathy. ^{1 2 4 9 10}

What is the purpose of this trial?

The goal of this clinical trial is to learn if sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, works to treat symptomatic, nonobstructive hypertrophic cardiomyopathy (noHCM) in adult patients. It will also learn about the safety of sotagliflozin in this patient population. The main questions it aims to answer are: 1. Will sotagliflozin be well tolerated in patients with nonobstructive HCM? 2. Will sotaglifozin improve exercise capacity, diastolic dysfunction and/or physical functioning in patients with nonobstructive HCM? 3. Will sotagliflozin improve circulating markers of cardiac metabolism in patients with nonobstructive HCM? Researchers will compare sotagliflozin to a placebo (a look-alike substance that contains no drug) to see if sotagliflozin is effective at treating hypertrophic cardiomyopathy (HCM). Participants will: Take sotagliflozin or a placebo every day for 12 weeks. They will then cross-over (or switch) to taking placebo or sotagliflozin (whichever one they did not take initially) for an additional 12 weeks. Visit the clinic once every 4-12 weeks for checkups, surveys, and tests including a stress test and echocardiogram.

Research Team

Sharlene Day, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

Adults with nonobstructive hypertrophic cardiomyopathy (HCM) who can take oral medication, agree to use effective contraception if applicable, and have a stable medical therapy. They must have good heart function as shown by tests and be experiencing certain symptoms or reduced exercise capacity.

Inclusion Criteria

I have signed and dated the consent form.

I can take pills and will follow the study's treatment plan.

I have been using effective birth control for at least a month and agree to continue during and 2 weeks after the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive either sotagliflozin or placebo daily for 12 weeks

12 weeks

Visits every 4-12 weeks for checkups, surveys, and tests

Treatment Phase 2

Participants cross-over to receive the alternate treatment (sotagliflozin or placebo) for an additional 12 weeks

12 weeks

Visits every 4-12 weeks for checkups, surveys, and tests

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sotagliflozin

Trial Overview The trial is testing sotagliflozin against a placebo in patients with HCM. Participants will take the drug or placebo for 12 weeks, then switch to the other for another 12 weeks. The study checks if sotagliflozin improves tolerance, exercise ability, heart function, and cardiac markers.

Participant Groups

Group I: Sotagliflozin first phase, Placebo second phase Active Control 1 Intervention

Sotagliflozin 400 mg once daily will be administered in the first phase, matching placebo once daily will be administered in the second phase

Group II: Placebo first phase, Sotagliflozin second phase Placebo Group 1 Intervention

Matching placebo once daily will be administered in the first phase, Sotagliflozin 400 mg once daily will be administered in the second phase

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been shown to significantly reduce hospitalization and cardiovascular mortality in patients with heart failure with preserved ejection fraction (HFpEF), highlighting their efficacy in this common and serious condition.

The ongoing SOTA-P-CARDIA trial aims to determine if the benefits of the dual SGLT1/2 inhibitor sotagliflozin, previously observed in diabetic heart failure patients, can also be extended to non-diabetic patients with HFpEF, with a focus on changes in left ventricular mass and other important health metrics over a 6-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the SOTA-P-CARDIA Trial (ATRU-V): Sotagliflozin in HFpEF Patients Without Diabetes. Pérez, MS., Rodríguez-Capitán, J., Requena-Ibáñez, JA., et al.[2023]

Sotagliflozin, the first dual inhibitor of SGLT1 and SGLT2, has shown significant efficacy in reducing cardiovascular and heart failure events in patients with type 2 diabetes, as demonstrated in the SOLOIST-WHF trial with a hazard ratio of 0.67.

While sotagliflozin expands treatment options for heart failure, existing SGLT2 inhibitors like dapagliflozin and empagliflozin have more robust evidence supporting their use, particularly in heart failure and chronic kidney disease, indicating that further research is needed to clarify sotagliflozin's role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotagliflozin: Efficacy, Safety, and Potential Therapeutic Applications in Heart Failure. Long, A., Salvo, M.[2023]

In a study of 5453 patients with type 2 diabetes and recent heart failure, only about 27.2% met the strict eligibility criteria for sotagliflozin, while around 62.8% were eligible under more pragmatic criteria, indicating a significant gap in trial eligibility versus real-world applicability.

Eligible patients for sotagliflozin had more severe heart failure and higher rates of cardiovascular events, suggesting that while the drug may be effective, its benefits could be particularly important for those with more advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eligibility for sotagliflozin in a real-world heart failure population based on the SOLOIST-WHF trial enrolment criteria: data from the Swedish heart failure registry. Becher, PM., Savarese, G., Benson, L., et al.[2023]

Sotagliflozin demonstrated significant cardiovascular benefits in type 2 diabetes patients with heart failure, showing a reduction in heart failure events and major adverse cardiovascular events compared to other treatments like dapagliflozin and empagliflozin, based on a meta-analysis of 11 studies involving 30,952 patients.

The safety profile of sotagliflozin was acceptable, with no increased risk of diabetic ketoacidosis or urinary tract infections, although it did present a mild risk of diarrhea compared to placebo, making it a viable option for managing T2DM in patients with heart failure or cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis. Li, J., Zhu, C., Liang, J., et al.[2023]

Sodium-glucose co-transporter-2 inhibitors (SGLT2is) like dapagliflozin, empagliflozin, and sotagliflozin may help reduce hospitalizations and cardiovascular mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF), based on evidence from larger heart failure trials that included this subgroup.

Despite the promising potential of SGLT2is for HFmrEF, more dedicated trials are necessary to confirm their efficacy and understand the mechanisms behind their cardioprotective effects, as current evidence is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promise of sodium-glucose co-transporter-2 inhibitors in heart failure with mildly reduced ejection fraction. Shen, X., Shen, X.[2022]

Sotagliflozin significantly increases the risk of genital mycotic infections in both type 1 and type 2 diabetes patients, with a relative risk of 3.49 for type 1 and 2.83 for type 2, indicating a notable safety concern associated with its use.

The drug also raises the risk of acidosis-related events in type 1 diabetes patients, with a relative risk of 7.49 for diabetic ketoacidosis, while showing no increased risk for these events in type 2 diabetes patients, suggesting different safety profiles based on diabetes type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of sotagliflozin in the therapy of diabetes mellitus type 1 and type 2: A meta-analysis of randomized trials. Zhou, F., Du, N., Zhou, L., et al.[2022]

Sotagliflozin, a new medication for diabetes, was found to be safe for renal function, showing no significant adverse effects on kidney health in a review of 14 studies involving 17,574 participants, including those with existing renal impairment.

The drug did not significantly change urinary albumin excretion or the risk of composite renal events, indicating that while it is safe, more research is needed to fully understand its effectiveness in preventing diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the dual sodium-glucose co-transporter-1 and -2 inhibitor sotagliflozin on renal outcomes in type 1 diabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Bantounou, MA., Sardellis, P., Thuemmler, R., et al.[2023]

Dapagliflozin, an SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes.

In the DAPA-HF trial, dapagliflozin was well tolerated and demonstrated a lower risk of worsening heart failure or cardiovascular death compared to placebo, making it a valuable treatment option for adults with symptomatic HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. Blair, HA.[2022]

Sotagliflozin, a dual SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death and hospitalizations for heart failure in patients with type 2 diabetes, as demonstrated in the SOLOIST-WHF trial.

In the SCORED trial, sotagliflozin not only lowered glycated hemoglobin levels in patients with severe renal impairment but also reduced the risk of stroke by 34%, highlighting its potential benefits across various stages of kidney disease and cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insights Into the Results of Sotagliflozin Cardiovascular Outcome Trials: Is Dual Inhibition the Cherry on the Cake of Cardiorenal Protection? Koufakis, T., Mustafa, OG., Tsimihodimos, V., et al.[2022]

In a small study of 36 patients with type 2 diabetes and heart failure, canagliflozin showed improvements in lean peak oxygen consumption and ventilatory anaerobic threshold compared to sitagliptin, indicating potential benefits for cardiorespiratory fitness.

Although canagliflozin did not significantly improve the primary endpoints of peak oxygen consumption or VE/VCO2 slope, it did lead to a notable reduction in heart failure-related quality of life, suggesting it may still offer important benefits for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The CANA-HF study. Carbone, S., Billingsley, HE., Canada, JM., et al.[2021]

References

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

Rationale and Design of the SOTA-P-CARDIA Trial (ATRU-V): Sotagliflozin in HFpEF Patients Without Diabetes. [2023]

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

Sotagliflozin: Efficacy, Safety, and Potential Therapeutic Applications in Heart Failure. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Eligibility for sotagliflozin in a real-world heart failure population based on the SOLOIST-WHF trial enrolment criteria: data from the Swedish heart failure registry. [2023]

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

Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis. [2023]

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

Promise of sodium-glucose co-transporter-2 inhibitors in heart failure with mildly reduced ejection fraction. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The safety of sotagliflozin in the therapy of diabetes mellitus type 1 and type 2: A meta-analysis of randomized trials. [2022]

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

Effect of the dual sodium-glucose co-transporter-1 and -2 inhibitor sotagliflozin on renal outcomes in type 1 diabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. [2023]

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

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. [2022]

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

Insights Into the Results of Sotagliflozin Cardiovascular Outcome Trials: Is Dual Inhibition the Cherry on the Cake of Cardiorenal Protection? [2022]

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

The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The CANA-HF study. [2021]