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

• ClinicalTrials.gov Identifier: NCT05058859
• Recruitment Status: Not yet recruiting
• First Posted: September 28, 2021
• Last Update Posted: September 21, 2023
• Sponsor: University of California, San Francisco
• Information provided by (Responsible Party): University of California, San Francisco

Tracking Information

• First Submitted Date: September 17, 2021
• First Posted Date: September 28, 2021
• Last Update Posted Date: September 21, 2023
• Estimated Study Start Date: August 1, 2024
• Estimated Primary Completion Date: August 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 17, 2021)

Change in cystine stone size over time (1 year and 3 months) [ Time Frame: 1 year and 3 months ]

The change in cystine stone size in mm will be measured over time using routine, standard-of-care imaging obtained during the management of patients with cystinuria.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long Term Clinical Efficacy of Sodium-glucose Cotransporter-2 (SGLT-2) Inhibitor in Cystinurics
• Official Title: Long Term Clinical Efficacy of Sodium-glucose Cotransporter-2 (SGLT-2) Inhibitor in Cystinurics

Brief 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.

Detailed Description

This is a single center, prospective cohort trial designed to assess the effect of daily oral administration of dapagliflozin 10 mg on cystine stone formation across routine imaging obtained during management of this disease. 25 subjects are planned, each with previously diagnosed cystinuria and without current treatment except with potassium citrate medication.

Each patient identified in the clinic as a potential participant will be screened to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be entered into the study. Consent will be obtained. The therapy under investigation, dapagliflozin 10 mg, will then be administered orally to each participant daily for one year. Each subject will be contacted 1 week by the study team after treatment begins to check compliance, tolerability, and side effects with SGLT-2 inhibitor therapy. Each subject will then be contacted every 8 weeks by the study team for follow-up and to continue checks on compliance, tolerability, and side effects with SGLT-2 inhibitor therapy. Each subject will subsequently undergo routine care with no further alterations or interruptions to their typical care with routine follow up appointments with a study doctor every 3-4 months.

Routine standard-of-care surveillance imaging for their cystinuria and formation of cystine stones will also occur as part of the treatment and management of each participant's kidney stone disease. This routine care will continue to be performed during the study period, the only difference being the collection of data with regard to ongoing stone burden for the cystinuria patients receiving treatment with daily oral dapagliflozin 10 mg on each routine imaging scan. Tolerability of the study therapy will be assessed at each routine visit during the participant's usual care. Participants who require operative intervention for their kidney stones during the treatment period will be removed from the study. No placebo will be used during this study.

Total duration of subject participation with be up to 1 year and 3 months. Total duration of the study is expected to be up to 1 year and 3 months.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cystinuria

Intervention

Drug: Dapagliflozin

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

Other Name: FARXIGA

Study Arms

Experimental: Study Drug

The study drug is Dapagliflozin

Intervention: Drug: Dapagliflozin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: September 17, 2021): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 1, 2026
• Estimated Primary Completion Date: August 1, 2025 (Final data collection date for primary outcome measure)

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)
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Victoria Hogue; 415-302-7443; Victoria.Hogue@ucsf.edu

Contact: Marshall Stoller, MD; Marshall.Stoller@ucsf.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05058859
• Other Study ID Numbers: SGLT2 1 Year
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of California, San Francisco
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, San Francisco
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Marshall Stoller, MD; University of California, San Francisco

• PRS Account: University of California, San Francisco
• Verification Date: September 2023