Clinical trial NCT04818034: The Effect of Sodium-glucose Cotransporter (SGLT) 2 Inhibitors on Cystine Stone Formation: A Preliminary Study
Official title: The Effect of Sodium-glucose Cotransporter (SGLT) 2 Inhibitors on Cystine Stone Formation: A Preliminary Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cystinuria
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2021-03-26
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This is a single center, proof of concept prospective cohort trial designed to assess the effect of daily oral administration of dapagliflozin on cystine formation in freshly voided urine. Five subjects are planned, each with previously diagnosed cystinuria and without current treatment except with potassium citrate medication.

Total duration of subject participation with be up to four weeks. Total duration of the study is expected to be 6 months.

Eligibility 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)
* 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.

Primary outcomes:
measure: Change in cysteine level in freshly voided urine
timeFrame: Samples collected at Initial visit and Day 7 visit, preserved and stored; mass spectometry analysis done over the course of 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Marshall Stoller
role: PRINCIPAL_INVESTIGATOR
References: