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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the diabetes drug Dapagliflozin, an SGLT-2 inhibitor, can help treat cystinuria, a condition where the kidneys produce painful cystine stones. Researchers propose that Dapagliflozin might prevent these stones by increasing glucose in the urine, potentially preventing or breaking apart cystine crystals. Individuals with a history of cystinuria and cystine kidney stones might be suitable candidates for this trial. The trial seeks to determine if this existing medication can offer a new method to reduce stone formation and associated pain. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that dapagliflozin, the drug under study, is generally safe for people. Other studies have demonstrated a good safety record for this drug. For instance, in patients with chronic kidney disease (CKD), dapagliflozin reduced the risk of serious kidney problems by 39%. Another study found that adding dapagliflozin to current treatments lowered protein levels in urine without causing harmful effects.

The FDA has already approved dapagliflozin for treating diabetes and heart failure, indicating it is usually well-tolerated. Although no published data exists on its effectiveness specifically for cystinuria, the dosage and use would match its approved treatments. This information supports the idea that dapagliflozin is safe for those considering joining this clinical trial. ^{1 2 3 4 5}

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

Most treatments for cystinuria, like high fluid intake and certain medications to alkalinize urine, aim to reduce cystine stone formation by managing cystine concentration. But dapagliflozin works differently, offering a fresh approach. It's a SGLT-2 inhibitor traditionally used for diabetes, and researchers are excited because it might reduce cystine stone formation by altering cystine handling in the kidneys. This unique mechanism could provide a novel way to manage cystinuria, potentially improving patient outcomes compared to current options.

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

Research shows that dapagliflozin, the study drug in this trial, may help with kidney problems. Studies have found it can lower the risk of serious kidney issues by 39% in people with chronic kidney disease (CKD). Although specific data on its use for cystinuria is lacking, its mechanism suggests potential benefits. By increasing sugar in the urine, dapagliflozin could prevent cystine stones from forming by breaking the cystine bond. This concept is based on its approved use for diabetes and heart failure, where it aids by altering sugar levels in the kidney. ^{4 5 6 7 8}

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 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.

I have had cystine kidney stones in the past.

You have been diagnosed with cystinuria based on tests of your urine or kidney stones.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 (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 (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, 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/PMC10370422/

Clinical Efficacy of Dapagliflozin in the Treatment ...

This study aimed to analyze the clinical efficacy of dapagliflozin in the treatment of diabetic kidney disease and its impact on proteinuria levels in patients.

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.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8729835/

Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease

Among 136 (62%) patients with baseline UACR>30 mg/g, dapagliflozin 5 mg and 10 mg resulted in relative reductions in UACR of 47% (21% to 65%) and 38% (10% to ...

7.

journals.lww.com

journals.lww.com/jasn/fulltext/2024/10001/efficacy_and_safety_of_dapagliflozin_in_the.2422.aspx

Efficacy and Safety of Dapagliflozin in the Treatment of...

Dapagliflozin in addition to optimized RAAS inhibition significantly reduced proteinuria in patients with IgAN over 6 months without evidence of adverse events.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8966174/

The clinical efficacy and safety of dapagliflozin in patients ...

A large cardiovascular outcome trial demonstrated that dapagliflozin also significantly reduced the risks of heart failure and progression of ...