The Effect of Sodium-glucose Cotransporter (SGLT) 2 Inhibitors on Cystine Stone Formation: A Preliminary Study

NCT04818034 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SGLT2
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Cystinuria is an inherited autosomal recessive disorder of the kidney that is the result of an inability to reabsorb cystine from the urine. Supersaturation of cystine in the urine produces crystals that precipitate and form stones in the kidney, which can be a cause of obstruction, infection, and chronic kidney disease. Cystine stones constitute a major health challenge for affected individuals with cystinuria because of the frequent recurrence of painful symptoms and the current absence of effective, patient-accepting treatment. A mainstay of therapy is breaking or preventing the cystine bond on the molecular level such that cystine (which is formed from the joining of two cysteine amino acids and their corresponding sulfur atoms) cannot precipitate in the urine. It is hypothesized that a glucose molecule may be able to do this if introduced into the urine. SGLT-2 inhibitors are a class of drug that are FDA approved to treat diabetes mellitus (DM) and heart failure by inhibiting an enzyme in the kidney that allows for reabsorption of glucose from the urine. This effectively increases the concentration of glucose in the urine. Our hypothesis suggests that administration of this drug to patients with cystine will introduce sufficient glucose into the urine to prevent the formation of cystine stones. To date, there has been no published data on the effectiveness of this therapy for this indication, although the dosage and administration would be identical to that already approved by the FDA for the treatment of DM and heart failure.

Conditions

Cystinuria

Outcome Measures

Primary Outcomes (1)

• 24hr Urine Measurements of the Effect of SGLT-2 Inhibitor Therapy on Cystine Production in Urine in Patients With Cystinuria

  The primary efficacy endpoint will be assessed by comparing previous 24hr urine cystine concentration data collected prior to study participation and 24hr urine concentration data collected after being on the study drug, specifically examining the content of cystine in the urine but not exclusively.

  1 month

Study Arms (1)

10 mg Dapagliflozin taken orally once daily for 4 weeks

EXPERIMENTAL

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

Drug: Dapagliflozin

Interventions

Dapagliflozin DRUG

Dapagliflozin is to lower blood sugar levels in adults with type 2 diabetes.

Also known as: FARXIGA

10 mg Dapagliflozin taken orally once daily for 4 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• males and females age 18 or older
• documented cystinuria on prior 24-hour urine collection and/or stone analysis
• history of previous cystine kidney stones
• able and willing to provide consent

You may not qualify if:

• prior diagnosis of diabetes mellitus (type I or type II)
• current SGLT-2 inhibitor administration at the time of screening
• SGLT-2 inhibitor administration within the last year prior to screening
• vulnerable populations including incarceration status
• anticipation of pregnancy during the study duration
• unable to give informed consent
• non-English primary language
• pregnancy, lactation, or child- bearing age without birth control devices
• serious illness likely to cause death within the next 5 years.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Cystinuria

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Renal Aminoacidurias; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

Our study has several important limitations. First, this was a retrospective study with a limited follow up duration on SGLT2 inhibitors. Second, treating the stone event rate as its own control may introduce healthcare utilization bias as interfacing with the medical system could have led to improved dietary habits which had a major impact on stone event rates. Third, patients with cystinuria are known to develop symptomatic calculi in clusters for unknown reasons. The sample size is small.

Results Point of Contact

• Title: Marshall Stoller
• Organization: University of California, San Francisco

victoria.hogue@ucsf.edu

415-514-0918

Study Officials

• Marshall Stoller

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2021
• First Posted: March 26, 2021
• Study Start: August 30, 2021
• Primary Completion: December 13, 2021
• Study Completion: April 28, 2022
• Last Updated: October 16, 2025
• Results First Posted: October 8, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)