SGLT2 Inhibitors for Cystinuria

Overseen By Max Bowman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: SGLT-2 inhibitors

Disqualifiers: Diabetes, Pregnancy, Serious illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called dapagliflozin to determine if it can treat cystinuria, a condition where the kidneys can't properly process cystine, leading to painful kidney stones. Researchers believe dapagliflozin, already used for diabetes, might prevent these stones by increasing glucose in the urine. The trial seeks participants with a history of cystine kidney stones who are ready to try a new treatment option. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently taking SGLT-2 inhibitors, you cannot participate in the trial.

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

Previous studies have shown dapagliflozin to be safe for humans. The FDA has already approved this drug for treating diabetes and heart failure. Research suggests it is generally safe, though some individuals might experience mild side effects like urinary tract infections or yeast infections.

Studies involving patients with chronic kidney disease have demonstrated that dapagliflozin can help protect the kidneys. This finding is promising for individuals with kidney issues, such as cystinuria. Overall, the drug is well-tolerated, and its approval for other conditions supports its safety in humans. ^{1 2 3 4 5}

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

Unlike standard treatments for cystinuria, which often focus on hydration, dietary changes, and medications like potassium citrate to manage stone formation, dapagliflozin offers a novel approach. Dapagliflozin is unique because it works as an SGLT2 inhibitor, a mechanism typically used to treat diabetes, that helps reduce the reabsorption of substances in the kidneys. Researchers are excited because this could potentially decrease cystine stone formation by altering kidney function in a new way, providing a fresh avenue for managing this challenging condition.

What evidence suggests that this treatment might be an effective treatment for cystinuria?

Research has shown that dapagliflozin, a type of medication, can lower the risk of serious kidney problems by 39% in people with chronic kidney disease. This drug increases the amount of sugar in the urine, which can prevent the formation of harmful substances that lead to kidney stones. For those who frequently develop kidney stones, dapagliflozin treatment is associated with a 25% reduction in the excretion of harmful oxalate in the urine. Although specific data on its effectiveness for cystinuria is lacking, the mechanism of dapagliflozin suggests it might help prevent cystine stones by increasing sugar in the urine. This increase may stop cystine from forming stones. Participants in this trial will receive 10 mg of dapagliflozin taken orally once daily for 4 weeks to evaluate its potential benefits for cystinuria. ^{1 3 4 6 7}

Who Is on the Research Team?

Marshall Stoller, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with cystinuria, documented by urine tests or stone analysis, and a history of cystine kidney stones. It's not for non-English speakers, pregnant or lactating individuals without birth control, those unable to consent, prisoners, diabetics, current or recent SGLT-2 inhibitor users, or anyone with serious illness likely to cause death within 5 years.

Inclusion Criteria

Able and willing to provide consent

able and willing to provide consent

You have been diagnosed with cystinuria based on a urine test or stone analysis.

Exclusion Criteria

I am currently taking SGLT-2 inhibitors.

Non-English primary language

Pregnancy, lactation, or child-bearing age without birth control devices

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive daily oral administration of dapagliflozin to assess its effect on cystine formation in urine

4 weeks

Initial visit, Day 7 visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin

Trial Overview The study is testing if Dapagliflozin (an FDA-approved diabetes drug) can prevent the formation of cystine stones in the kidneys by increasing glucose levels in urine. This preliminary study will explore whether this treatment could be an effective option for patients with cystinuria.

How Is the Trial Designed?

Group I: 10 mg Dapagliflozin taken orally once daily for 4 weeks Experimental Treatment 1 Intervention

10 mg of the study drug Dapagliflozin taken orally once daily for 4 weeks

Dapagliflozin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Forxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in United States as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in Canada as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

SGLT2 inhibitors significantly reduce the risk of acute kidney injury (RR 0.75) and show a trend towards lower severe hypoglycemia risk (RR 0.86), indicating a safety benefit in patients with chronic diseases.

However, SGLT2 inhibitors are associated with increased risks of diabetic ketoacidosis (RR 2.57), genital infections (RR 3.75), and volume depletion (RR 1.14), suggesting that these specific adverse events should be closely monitored in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of four SGLT2 inhibitors in three chronic diseases: A meta-analysis of large randomized trials of SGLT2 inhibitors. Qiu, M., Ding, LL., Zhang, M., et al.[2022]

SGLT-2 inhibitors, originally designed to lower blood sugar, have shown significant efficacy and safety in protecting cardiovascular and renal health in patients with chronic kidney disease (CKD), beyond just their glucose-lowering effects.

The review highlights five specific SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, and sotagliflozin) that have been tested in cardiovascular outcome trials and are approved for use in Europe and North America, demonstrating their potential benefits in managing heart failure and CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium-glucose co-transporter 2 inhibitors in patients with chronic kidney disease. Solomon, J., Festa, MC., Chatzizisis, YS., et al.[2023]

Dapagliflozin effectively lowers blood sugar levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, with a low risk of hypoglycemia and additional benefits like weight loss and reduced blood pressure.

While it is generally safe, dapagliflozin can increase the risk of genital infections, particularly in women, and its efficacy may be reduced in patients with kidney issues; ongoing trials are investigating its potential cardiovascular and renal protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. Scheen, AJ.[2021]

SGLT-2 inhibitors have shown potential nephroprotective effects, particularly in diabetic patients with chronic kidney disease (CKD), as confirmed by the CREDENCE study which demonstrated reduced progression to dialysis in patients with impaired kidney function.

The DAPA-CKD study was halted early due to significant nephroprotective effects of dapagliflozin in CKD patients, leading to new treatment guidelines recommending SGLT-2 inhibitors as standard care for diabetic CKD patients, despite their current lack of approval for those with severely reduced kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antidiabetic SGLT-2 inhibitors prevent progression of chronic kidney disease]. Heine, GH.[2021]

SGLT2 inhibitors represent a promising treatment for type 1 and type 2 diabetes by blocking glucose reabsorption in the kidneys, leading to increased glucose and energy loss through urine, which can help manage hyperglycemia and obesity.

Research indicates that SGLT2 inhibitors are generally safe for kidney function, as evidenced by individuals with familial renal glycosuria who maintain normal kidney health, suggesting that these medications may not adversely affect renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium-glucose co-transporter-2 inhibitors: an emerging new class of oral antidiabetic drug. Idris, I., Donnelly, R.[2021]

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

Dapagliflozin, an SGLT2 inhibitor, significantly reduced the risk of severe kidney outcomes by 39% in patients with chronic kidney disease (CKD), demonstrating its effectiveness regardless of diabetes status.

In addition to its renal benefits, dapagliflozin also lowered the risk of cardiovascular events and all-cause mortality by 29% and 31%, respectively, although there is a noted risk of adverse effects like ketoacidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin for the treatment of chronic kidney disease. Kurata, Y., Nangaku, M.[2022]

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

SGLT2-inhibitors, like dapagliflozin, represent a promising new class of oral medications for type 2 diabetes, effectively lowering HbA1c levels without increasing the risk of hypoglycemia, and also contributing to weight loss and reduced blood pressure.

However, there are safety concerns associated with SGLT2-inhibitors, including an increased risk of genital and urinary tract infections, as well as potential links to bladder and breast cancer, which have led to regulatory scrutiny and the need for further large-scale trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2-inhibitors: a novel class for the treatment of type 2 diabetes introduction of SGLT2-inhibitors in clinical practice. Cuypers, J., Mathieu, C., Benhalima, K.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04818034?cond=Cystinuria&viewType=Table&rank=10

The Effect of Sodium-glucose Cotransporter (SGLT) 2 ... This is a single center, proof of concept prospective cohort trial designed to assess the effect of daily oral administration of dapagliflozin on cystine ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12021238/

Dapagliflozin treatment in recurring kidney stone patients Dapagliflozin therapy is associated with a reduction of oxalate excretion in 24-hour urine by at least 25% compared to the baseline value in ...

3. withpower.com withpower.com/trial/phase-3-cystinuria-8-2021-aebf8

SGLT2 Inhibitors for Cystinuria · Info for Participants Dapagliflozin, an SGLT2 inhibitor, significantly reduced the risk of severe kidney outcomes by 39% in patients with chronic kidney disease (CKD), demonstrating ...

4. thelancet.com thelancet.com/journals/lanepe/article/PIIS2666-7762(24)00013-9/fulltext

Long-term benefits of dapagliflozin on renal outcomes ... New-users of dapagliflozin had significantly lower rates of new-onset CKD, loss of kidney function, and a composite renal outcome. Results were ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024816

Dapagliflozin in Patients with Chronic Kidney Disease The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.

6. withpower.com withpower.com/trial/phase-3-cystinuria-11-2021-a861a

SGLT-2 Inhibitor for Cystinuria · Info for Participants Dapagliflozin, used for type 2 diabetes and chronic kidney disease, is generally safe but may cause mild urinary tract infections and mycotic genital infections ...

7. academic.oup.com academic.oup.com/ckj/article/18/1/sfae396/7915991

Efficacy and safety of dapagliflozin in patients with CKD Albuminuria declined by 25.1% (95%CI 23.0–27.2) from 500 mg/day [IQR 225–1425] to 320 mg/day [IQR 100–900]. Albuminuria reduction was ≥30% in 48.3% of patients, ...