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

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ClinicalTrials.gov Identifier: NCT04818034
Recruitment Status : Not yet recruiting
First Posted : March 26, 2021
Last Update Posted : March 26, 2021
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

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.


Condition or disease Intervention/treatment Phase
Cystinuria Drug: Dapagliflozin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Sodium-glucose Cotransporter (SGLT) 2 Inhibitors on Cystine Stone Formation: A Preliminary Study
Estimated Study Start Date : June 1, 2021
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : June 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Study Drug
The study drug Dapagliflozin
Drug: Dapagliflozin
Dapagliflozin is to lower blood sugar levels in adults with type 2 diabetes.
Other Name: FARXIGA




Primary Outcome Measures :
  1. Change in cysteine level in freshly voided urine [ Time Frame: Samples collected at Initial visit and Day 7 visit, preserved and stored; mass spectometry analysis done over the course of 6 months ]
    Utilizing mass spectrometry, the research team will determine the effect of SGLT-2 inhibitor therapy on quantitative sulfur as a surrogate for presence of cysteine in freshly voided urine in patients with cystinuria. This will be assessed by comparing the qualitative and quantitative differences between the mass spectrometry output data between the participants' freshly voided urine at the initial visit and at the follow up visit after initiation of SGLT-2 inhibitor therapy, specifically examining the quantitative sulfur content between the two samples as a surrogate for cysteine in the urine.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04818034


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

Locations
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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Contact: Victoria Hogue    415-302-7443    victoria.hogue@ucsf.edu   
Principal Investigator: Marshall Stoller, MD         
Sub-Investigator: Max Bowman, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
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Principal Investigator: Marshall Stoller University of California, San Francisco
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04818034    
Other Study ID Numbers: SGLT2
First Posted: March 26, 2021    Key Record Dates
Last Update Posted: March 26, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Cystinuria
Renal Aminoacidurias
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs