Empagliflozin for Kidney Stones

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Chicago

Must not be taking: Diuretics, Alkali, Topiramate

Disqualifiers: Brushite, Uric acid, Cysteine, others

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

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether empagliflozin, a drug typically used for diabetes, can prevent kidney stones by altering urine factors. Researchers aim to determine its effects on individuals with a history of calcium-based kidney stones, specifically calcium oxalate and calcium phosphate stones. Participants will take the drug for four weeks, and their urine will be tested for changes in factors affecting stone formation, such as citrate levels. This study could pave the way for larger trials in the future for kidney stone prevention. It suits those who have experienced calcium oxalate or calcium phosphate kidney stones. As an Early Phase 1 trial, this research focuses on understanding how empagliflozin works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

If you are taking diuretic medication or alkali supplements, you will need to stop them for the study period. Also, if you use drugs that affect kidney function, like topiramate, you cannot participate.

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

Research has shown that empagliflozin, a medication for diabetes and heart conditions, has promising safety results. Studies have found that empagliflozin can significantly lower the risk of kidney stones in people with type 2 diabetes, with about a 40% reduction in kidney stone events compared to those not taking the drug. This suggests that empagliflozin may help prevent stone formation.

However, while empagliflozin appears to reduce the risk of kidney stones, it may increase the chances of urinary tract infections and genital skin infections. Some users have reported these side effects. Although the medication is generally well-tolerated, potential participants should be aware of these risks.

The study will explore whether the same positive effects on kidney stones apply to those who have had calcium-based stones, such as calcium oxalate or phosphate stones. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney stones?

Most treatments for kidney stones primarily focus on pain management and facilitating the passage of stones through hydration and medications like alpha-blockers. However, empagliflozin is unique because it targets the underlying causes of stone formation. While traditional treatments don't directly address stone composition, empagliflozin may help regulate the body's handling of calcium and phosphate, potentially reducing the formation of stones. Researchers are excited about this approach because it could offer a more proactive solution, possibly preventing stones before they form, rather than just treating the symptoms.

What evidence suggests that empagliflozin might be an effective treatment for kidney stones?

Research has shown that empagliflozin might help lower the risk of kidney stones. One study found that people taking empagliflozin had about a 40% lower chance of developing kidney stones compared to those who didn't take it. In individuals without diabetes, empagliflozin improved urine factors that reduce the likelihood of kidney stone formation. Other studies have found that the rate of kidney stone events was 30-50% lower in patients using empagliflozin. This trial will evaluate empagliflozin in patients with a history of calcium-based kidney stones, specifically those with calcium phosphate or calcium oxalate stones, to further explore its potential benefits. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for people who have had calcium-based kidney stones, specifically calcium oxalate or calcium phosphate stones. It's not clear what the specific inclusion and exclusion criteria are, but typically participants would need to be in stable health and meet certain medical requirements.

Inclusion Criteria

I am between 18-70 years old and have had a calcium phosphate kidney stone.

I am between 18-70 years old and have had a kidney stone that was mostly calcium oxalate.

I understand the importance of sex differences in kidney stone studies due to variations in stone type and acid-base handling.

Exclusion Criteria

History of severe acid-base abnormality, very low (less than 100mg/day) or very high (greater than 1500mg/day) urine citrate

My kidneys do not work well (eGFR <60).

I have had kidney stones made of brushite, uric acid, cysteine, or struvite.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take empagliflozin 10 mg once daily for 4 weeks and collect 24-hour urine samples before and after treatment

4 weeks

2 visits (in-person), 1 check-in (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview The study tests if empagliflozin (Jardiance®), a diabetes drug, can change factors leading to kidney stone formation. Participants will take the medication daily for 4 weeks while researchers monitor changes in their urine that could affect stone risk.

How Is the Trial Designed?

Group I: CaP (Calcium Phosphate) stone patients Active Control 1 Intervention

Defined as \>50% calcium phosphate content on most recent stone analysis Age 18-70 years

Group II: CaOx (Calcium Oxalate) stone patients Active Control 1 Intervention

Defined as \>50% calcium oxalate content on most recent stone analysis Age 18-70 years

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9202688/

Empagliflozin and Decreased Risk of Nephrolithiasis In summary, we demonstrate that the use of empagliflozin was associated with an approximate 40% reduced risk of renal stone disease as compared with placebo.

2. nature.com nature.com/articles/s41591-024-03330-x

Empagliflozin in nondiabetic individuals with calcium and ... In conclusion, empagliflozin significantly improved the urinary lithogenic risk profile in nondiabetic patients with calcium and UA kidney ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04911660

Impact of the SGLT2 Inhibitor Empagliflozin on Urinary ... Interestingly, in pooled analyses of phase I, II and III trials, the rate of kidney stone events tended to be 30-50 % lower in patients treated with 10 or 25 ...

4. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2814491

SGLT2 Inhibitors and Nephrolithiasis Risk in Type 2 Diabetes However, a study of healthy volunteers treated with empagliflozin, 10 mg, reported lower urinary pH after 4 weeks of treatment. Third, SGLT2i ...

5. journalrip.com journalrip.com/Inpress/jrip-32292.pdf

The effect of SGLT2 inhibitors on kidney stones Primary outcome​​ SGLT2 inhibitors administration reduced the risk of kidney calculi by 20% and prevented kidney stone disease (OR = 0.80, 95% CI ...

6. diabetesjournals.org diabetesjournals.org/care/article/48/2/193/157601/Risk-of-Nephrolithiasis-Associated-With-SGLT2

Risk of Nephrolithiasis Associated With SGLT2 Inhibitors ... Over a mean of 654 days, the risk of nephrolithiasis was lower in SGLT2i initiators than in DPP4i initiators: 0.65 vs. 1.12 events per 100 ...

7. auajournals.org auajournals.org/doi/10.1097/JU.0000000000004578

Endourology and Nephrolithiasis While these drugs seem to reduce stone risk, they are associated with an increased risk of UTI and genital skin infections. References. 1.