SGLT-2 Inhibitor for Cystinuria

Overseen By Victoria Hogue

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

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: 5

Duration: 1 year

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests whether taking dapagliflozin daily can help people with cystinuria, a genetic kidney disorder that causes painful kidney stones. Dapagliflozin increases sugar levels in the urine, which may help stop or break down the stones. The study will monitor patients to see if this treatment works.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Dapagliflozin for treating cystinuria?

Dapagliflozin, a drug that helps lower blood sugar in type 2 diabetes, has shown benefits for kidney health and reducing heart-related risks in people with chronic kidney disease. While it is not directly studied for cystinuria, its kidney-protective effects might be relevant. ^{1 2 3 4 5}

Is dapagliflozin generally safe for humans?

Dapagliflozin, used for type 2 diabetes and chronic kidney disease, is generally safe but may cause mild urinary tract infections and mycotic genital infections, especially in women. ^{1 2 6 7 8}

How is the drug Dapagliflozin unique for treating cystinuria?

Dapagliflozin is unique because it is an SGLT-2 inhibitor, originally used to lower blood sugar in diabetes by preventing glucose reabsorption in the kidneys, which may also help in managing kidney-related conditions like cystinuria by promoting the excretion of substances through urine. ^{1 2 3 9 10}

Research Team

Marshall Stoller, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults over 18 with a history of cystine kidney stones and confirmed cystinuria. Participants must be able to consent and not have diabetes, be pregnant or likely to become so without birth control, seriously ill, non-English speaking, incarcerated, or unable to give informed consent.

Inclusion Criteria

I have had cystine kidney stones in the past.

Able and willing to provide consent

I have had cystine kidney stones in the past.

Exclusion Criteria

You have a serious illness that is likely to cause death within the next 5 years.

Anticipation of pregnancy during the study duration

I am unable to understand and agree to the study's procedures and risks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Daily oral administration of dapagliflozin 10 mg to prevent or reverse cystine stone formation

1 year

1 visit (in-person) at start, followed by contact every 8 weeks

Follow-up

Participants are monitored for safety, compliance, and effectiveness after treatment

3 months

Routine follow-up appointments every 3-4 months

Treatment Details

Interventions

• Dapagliflozin

Trial Overview The trial tests if Dapagliflozin, an FDA-approved drug for diabetes and heart failure that increases urine glucose levels can prevent or dissolve cystine stones in the kidneys by introducing enough glucose into the urine.

Participant Groups

Group I: Study Drug Experimental Treatment 1 Intervention

The study drug is Dapagliflozin

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+

Findings from Research

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]

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]

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]

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]

Dapagliflozin (DAPA) is an effective SGLT2 inhibitor for treating type 2 diabetes, showing favorable pharmacokinetics and pharmacodynamics that help lower blood sugar levels while having beneficial effects on other metabolic risk factors.

While DAPA is generally safe, it carries an increased risk of genital and urinary infections, and concerns about bladder cancer and cardiovascular safety remain, prompting the FDA to seek further data on these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Maranghi, M., Carnovale, A., Durante, C., et al.[2021]

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]

Dapagliflozin (Forxiga) is no longer authorized for the treatment of type 1 diabetes mellitus, indicating a significant change in its regulatory status.

This decision reflects safety concerns or efficacy issues that may have arisen from clinical evaluations or post-marketing surveillance, emphasizing the importance of ongoing drug safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin no longer licensed for type 1 diabetes. [2022]

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]

References

1. Belgium pubmed.ncbi.nlm.nih.gov

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

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

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

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

Sodium-glucose co-transporter 2 inhibitors in patients with chronic kidney disease. [2023]

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

Effects of sodium-glucose cotransporter 1 and 2 inhibitors on cardiovascular and kidney outcomes in type 2 diabetes: A meta-analysis update. [2021]

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

SGLT2-inhibitors: a novel class for the treatment of type 2 diabetes introduction of SGLT2-inhibitors in clinical practice. [2021]

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

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]

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

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Dapagliflozin no longer licensed for type 1 diabetes. [2022]

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

SGLT2 Inhibition and Uric Acid Excretion in Patients with Type 2 Diabetes and Normal Kidney Function. [2023]

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

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