SGLT2 Inhibitors for Duchenne Muscular Dystrophy

(CHERISH Trial)

Overseen By Jennifer Howell, RN

Age: < 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Larry W. Markham

Must not be taking: Investigational therapies

Disqualifiers: Heart failure, Type 1 diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how empagliflozin, an SGLT2 inhibitor typically used for heart issues in adults, can treat heart problems in children with Duchenne muscular dystrophy (DMD). Researchers aim to understand how these patients absorb and process the drug to determine the correct dosage. The trial is suitable for children with DMD who meet specific heart imaging criteria and are in relatively good heart health. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants an opportunity to contribute to groundbreaking research.

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 be on any investigational therapy that affects heart function.

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

Research has shown that SGLT2 inhibitors, such as empagliflozin, are being tested for safety in people with Duchenne muscular dystrophy (DMD). In one study, most patients tolerated the drug well, though a few discontinued due to side effects. This indicates that while many respond well to the treatment, some may experience issues.

Empagliflozin is already used to treat heart issues in adults, providing some insight into its safety, even though it is not specifically for DMD. The current trial is in its early stages, focusing on understanding how the drug works in the body rather than fully proving its safety. So far, the results are encouraging, but more information is needed about its safety in younger patients with DMD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Duchenne muscular dystrophy?

Unlike the standard treatments for Duchenne Muscular Dystrophy, which mainly focus on managing symptoms and slowing disease progression, SGLT2 inhibitors target a different pathway. Originally used for diabetes, SGLT2 inhibitors work by managing glucose levels, but researchers are now exploring their potential to improve muscle function and reduce inflammation in Duchenne patients. This new approach is exciting because it offers a fresh angle on tackling the disease, potentially leading to improved outcomes for those affected.

What evidence suggests that SGLT2 inhibitors might be an effective treatment for Duchenne muscular dystrophy?

Research has shown that SGLT2 inhibitors, such as empagliflozin, might improve heart function in people with Duchenne muscular dystrophy (DMD). Studies in mice suggest these drugs can slow heart problems related to DMD. Some evidence indicates they increase certain heart proteins, potentially enhancing heart function. Although the effectiveness in humans with DMD remains uncertain, early findings suggest that SGLT2 inhibitors are safe and well-tolerated in this group. This trial will explore different dosing strategies to identify the most effective dose for improving heart function in DMD patients. These promising results support further research into their use for heart issues in DMD. ^{1 2 3 4 6}

Who Is on the Research Team?

Larry W. Markham, MD

Principal Investigator

Riley Children's Hospital

Are You a Good Fit for This Trial?

This trial is for pediatric patients with Duchenne Muscular Dystrophy (DMD) who are experiencing heart problems. The study aims to understand how a drug called empagliflozin, which is not yet approved for children with DMD, works in their bodies.

Inclusion Criteria

Presence of late gadolinium enhancement (LGE) imaging by CMR

My Duchenne muscular dystrophy diagnosis was confirmed by muscle biopsy or genetic testing.

My heart's pumping ability is normal or slightly low.

Exclusion Criteria

History of ketoacidosis or hypersensitivity to SGLT2i therapy

I am not on any experimental treatments that could affect my heart.

I have a genetic condition that could affect my heart.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dosing

Initial dosing of 5 mg or 10 mg based on body weight to determine appropriate dosing for DMD patients

12 months

Regular visits for dosing and monitoring

Pharmacokinetics

Pharmacokinetic analysis to determine drug absorption, distribution, metabolism, and excretion

12 months

Regular blood sampling visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SGLT2 inhibitor

Trial Overview The focus of the trial is on empagliflozin, a medication typically used in adults for heart issues. Researchers want to see how this drug behaves in young DMD patients' bodies by studying its absorption, distribution, metabolism, and excretion.

How Is the Trial Designed?

Group I: Pharmacokinetics Experimental Treatment 1 Intervention

In the second stage, based on the Pharmacokinetics (PK) analysis results from the initial 6 subjects divided in 5 mg and 10 mg dose groups, the next dose will be determined, for which the remaining 4 subjects will be allocated. The next dose decision will be made based on the target drug concentration levels along with the estimated PK parameters (e.g., the area under the drug concentration time curve and the maximum concentration), which correspond to adults PK and drug levels.

Group II: Dosing Experimental Treatment 1 Intervention

At the initial stage, investigators will allocate 3 subjects to 5 mg and 3 subjects 10 mg depending on their body weight (i.e., 5 mg for children with weight les than 40 kg, 10 mg for those with greater than 40 kg).

Who Is Running the Clinical Trial?

Larry W. Markham

Lead Sponsor

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07172971

Sodium/Glucose Cotransporter-2 Inhibitors (SGLT2i) ... This is a pharmacokinetic study (PK Study) to better understand empagliflozin dosing in pediatric Duchenne muscular dystrophy patients.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7618122/

The sodium/glucose cotransporter 2 inhibitor empagliflozin ... The effectiveness of SGLT2 inhibitors in DMD cardiomyopathy is unexplored, but a first clinical trial (NCT06643442) has already been initiated.

3. heart.bmj.com heart.bmj.com/content/109/Suppl_6/A63

55 An audit of the use, understanding & tolerability ... Conclusions Our study provides unique early insights on the safety and tolerability of SGLT2 inhibitors in a DMD cohort.

4. journals.physiology.org journals.physiology.org/doi/full/10.1152/ajpheart.00707.2025

SGLT2 inhibitors to the rescue: restoring cardiac sodium ... Their data also reveal that SGLT2i increase NaV1.5 protein levels in muscular dystrophy, and although consistent with increased NaV1.5 mRNA expression in other ...

5. scholarworks.indianapolis.iu.edu scholarworks.indianapolis.iu.edu/items/74df6c0c-4675-418f-b55d-0c848f53ef51

The Effects of SGLT2 Inhibition on Cardiac Function in Mice ... Conclusions: These preliminary results suggest that SGLT2i may slow the progression of cardiac dysfunction in DMD. These encouraging results justify further ...

6. parentprojectmd.org parentprojectmd.org/wp-content/uploads/2023/03/Cardiac_meeting_report_PAGES_lores.pdf

2022 cardiac care and duchenne workshop report – How can researchers assess heart disease progression risk and compare individuals with. Duchenne and Becker muscular dystrophy (Becker) across their ...