Long Term Clinical Efficacy of Sodium-glucose Cotransporter-2 (SGLT-2) Inhibitor in Cystinurics

• Status: Not yet recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Cystinuria is an inherited autosomal recessive disorder of the kidney that is the result of an inability to reabsorb dibasic amino acids, including 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. The hypothesis suggests that administration of this drug to patients with cystinuria will introduce sufficient glucose into the urine to prevent or reverse 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Treatments: Dapagliflozin

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• prior diagnosis of diabetes mellitus (type I or type II)

• 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