This trial is evaluating whether Dapagliflozin will improve 1 primary outcome in patients with Cystinuria. Measurement will happen over the course of Samples collected at Initial visit and Day 7 visit, preserved and stored; mass spectometry analysis done over the course of 6 months.
This trial requires 10 total participants across 2 different treatment groups
This trial involves 2 different treatments. Dapagliflozin is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 2 and have already been tested with other people.
The data suggest that renal cystinosis can be cured for at least 1 year after the termination of treatment. Patients should be instructed about the recurrence of cystinosis during follow-up visits.
Although not a cure, an individual with cystinuria may avoid most complications with a low-ysine diet and can minimize the impact of the disease by eliminating the risk factors for worsening the disease. Therefore, management of this disease should start with eliminating the risk factors early.
About 1,100,000 Caucasian children in the United States in ages 5-19 (9.4% of population; 9.1% of men and 10% of women) may have Cystinuria, making them the third-most prevalent urological cause in this demographic. This finding does not take into account the prevalence of cystinuria in the elderly population (10% of males and 15% of females in age 65 and above). These studies are limited by the absence of cystinuria data in all states, and by the use of only laboratory tests to diagnose cystinuria. The prevalence of cystinuria in adult population seems uncertain.
Inherited risk of developing cystinuria has been demonstrated and may be due to a combination of genetic and environmental factors. We hypothesize that cystinuria has a genetically determined defect of the proximal tubule of the nephron. We suggest a multifactorial approach to cystinuria treatment and emphasize that pharmacological treatments are not necessarily required.
All children with unexplained developmental delay or motor skill disturbance should be questioned, including about urination problems, appetite impairment, or weight loss. Cystinuria should be suspected if the serum cystine level is less than the upper limit of the reference range, and this can be confirmed by the urine cystine-to- creatinine ratio. Children with cystinuria commonly present with developmental delay, but children with autosomal recessive cystinosis commonly present with symptoms of nephrocalcinosis and Fanconi's syndrome.
The major diagnostic criterion for cystinuria remains the demonstration of high urinary cystine levels (≥ 75 μmol/min). However, these levels could be missed in about 20% of cases. There is now a test (Diaz's cystine test) that shows an excellent diagnostic performance, even in those cases with borderline values. Cystinuria is an almost exclusively renal condition and should be considered only when the symptoms and the signs of deterioration are present.
Findings from a recent study suggest that the pharmacokinetics of dapagliflozin are influenced by CYP2C19 phenotype; a minor allele of CYP2C19 can lead to increased exposure to dapagliflozin. Because the pharmacokinetics and efficacy profile of dapagliflozin is maintained across CYP2C19 phenotypes, it appears to have no significant effect on clinical efficacy.
Clinical trials can play a role in determining treatments for Cystinuria but only by conducting clinical trials and reporting outcomes can Cystinuria be truly understood. Clinical trials can help patients to determine the best treatment regimen that will help minimize their symptoms but will help with the treatment of Cystinuria in general.
Dapagliflozin is safe for women who are pregnant, breastfeeding, have kidney disease or on other DM medications. For people not on DM medications and those who are not pregnant, no firm evidence of increased risk has been found. For people taking other DM medications, risks have not been established. For women taking dapagliflozin, kidney function should be checked regularly with a test that measures urinary albumin excretion. Women who have polycystic ovary syndrome (PCOS) should not take dapagliflozin but rather other options [such as metformin or metformin/gliflozin].
The most commonly occurring non-serious adverse events include constipation, headache, fatigue, vomiting, and a rash. The magnitude of these effects was generally mild to moderate, and no deaths or serious adverse events were reported.
There have been a small number of reports regarding CYSU in the last few years, but their overall findings have not influenced treatment; thus, there is no necessity to change treatment. Additional studies are warranted.
The vast majority of patients who are receiving DAP and concomitant CYP3A inhibitors are not receiving additional treatment. A minority of patients are being treated with one or more additional antidiabetes medications. The concurrent use of CYP3A inhibitors with DAP may have pharmacodynamic or pharmacokinetic implications if not carefully evaluated, which deserves further analysis.