Cystinuria
Conditions
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.
Interventions
DRUGDapagliflozin
Dapagliflozin is to lower blood sugar levels in adults with type 2 diabetes.
Sponsors
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24hr Urine Measurements of the Effect of SGLT-2 Inhibitor Therapy on Cystine Production in Urine in Patients With Cystinuria | 1 month | 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. |
Countries
United States
Participant flow
Recruitment details
The study team will identify the patients being treated for cystinuria within the study team's clinic. The study team will inform these patients of the study and provide them with the study details to allow further discussion and to answer any questions the patients might have.
Pre-assignment details
There is only one arm for this study. Any patient willing to participate in this study will be in that arm and will be given the study drug Dapagliflozin.
Participants by arm
| Arm | Count |
|---|---|
| Study Drug The study drug Dapagliflozin | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Study Drug |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
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.
Time frame: 1 month
Population: The analysis was specifically looking at cystine production in urine but other products were analyzed as well as shown in the table.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug | 24hr Urine Measurements of the Effect of SGLT-2 Inhibitor Therapy on Cystine Production in Urine in Patients With Cystinuria | 999.3 24hr urine cystine concentration (mg) | Standard Deviation 1.1 |
p-value: 0.965paired t-test