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Sotagliflozin to Slow Kidney Function Decline in Persons With Type 1 Diabetes and Diabetic Kidney Disease

RecruitingPhase 3Ages 18 Years - 75 YearsAllAlessandro Doria
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In plain words

What the trial is, and whether it could suit you

Powerful new drugs that can prevent or delay end stage kidney disease (ESKD) - so called sodium-glucose cotransporter-2 inhibitors (SGLT2i) - are now available for patients with type 2 diabetes. Whether these drugs have similar effects in patients with type 1 diabetes (T1D) remains unknown because of the few studies in this population, due to concerns about the increase in risk of diabetic ketoacidosis (DKA, a serious, potentially fatal acute complication of diabetes due to the accumulation of substances called ketone bodies) observed with SGLT2i therapy in T1D. One of the few T1D studies conducted to date showed that implementing an enhanced DKA prevention plan can reduce the risk of DKA associated with the SGLT2i sotagliflozin (SOTA) to very low levels. In the present study, a similar DKA prevention program will be used to carry-out a 3-year trial to test the kidney benefit of SOTA in

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📋 Eligibility rules (as published)
Inclusion Criteria: * Type1 diabetes (T1D) continuously treated with insulin within one year from diagnosis. * Duration of T1D ≥ 8 years; * eGFR based on serum creatinine and cystatin c (2021 serum creatinine-cystatin C CKD-EPI equation) between 20 and 60 ml/min/1.73 m2 at screening (with the option of a second eGFR measurement within 4 weeks from the first one if the eGFR was in the range of \>60 to ≤65 or ≥16 to \<20 ml/min/1.73 m2); * a. First morning void urinary albumin creatinine ratio (UACR) ≥200 mg/g at Screening or on repeat measurement within 4 weeks from the first one, or b. First morning void urinary UACR ≥100 mg/g at Screening or on repeat measurement within 4 weeks and at least one uACR \>=30 in the previous 2 years while treated with RASB at a stable dose; * HbA1c at screening \<10% (with the option of a second HbA1c measurement within 4 weeks from the first one if the HbA1c was ≤10.2%); * Receiving standard of care, including renin angiotensin system blockers (RASB) at a clinically appropriate dose, unless contraindicated or not tolerated. * Willing and able to comply with schedule of events and protocol requirements, including written informed consent, and willing to wear a continuous glucose monitoring (CGM) device for the entire duration of the study. * a. Blood pressure ≤155/95 mmHg at screening, or b. BP ≤155/95 mmHg at the end of the run-in period, or c. consistent BP ≤155/95 mmHg on home monitoring during the run-in period, as determined by study site investigator, despite BP values \>155/95 mmHg in clinic. Exclusion Criteria: * Type 2 diabetes or monogenic forms of diabetes or diabetes secondary to pancreatic disease; * Use of automated insulin delivery devices that are not approved by health regulatory agencies, or used in ways that do not align with manufacturer recommendations; * Use of any SGLT inhibitor in the previous 2 months; * Use of dual medication RASB therapy (spironolactone, eplerenone, finerenone are allowed in combination with RASB therapy); * Use of GLP-1 receptor agonists and other non-insulin glucose-lowering agents if not on stable dose for \> 2 months at screening (patients can be rescreened after being on stable dose for \> 2 months); * Use of anti tumor necrosis factor (TNF) alpha biologic medications at screening; * Known allergies, hypersensitivity, or intolerance to SOTA; * History of ≥3 severe hypoglycemic events (requiring third-party assistance for correction) within 3 months of screening; * History of diabetic ketoacidosis (DKA) or non-ketotic hyperosmolar state within 3 months of screening OR \>1 episode of DKA or non-ketotic hyperosmolar state within 12 months of screening; * Blood beta-hydroxybutyrate (BHB) \>0.6 mmol/L for \>2 hours on \>2 occasions during the Run-in period; * Inadequate beta hydroxybutyrate (BHB) testing (\<50% of the prescribed measurements) during Run-in; * History of primary renal glycosuria; * History of biopsy-proven non-diabetic chronic kidney disease (CKD); * History of kidney transplant or currently on chronic dialysis; * Current or past history of decompensated cirrhosis (defined as variceal bleeding, ascites or hepatic encephalopathy), and/or known diagnosis of cirrhosis based on liver biopsy, imaging, or elastography, and/or aspartate aminotransferase (AST) or alanine transaminase (ALT) at screening \>2 times upper limit of normal, and/or total bilirubin at screening \>1.3 times upper limit of normal). * History of severe acquired immune deficiency syndrome or human immunodeficiency virus (HIV) infection or severely immunocompromised status; * Cancer treatment (excluding non-melanoma skin cancer treated by excision, carcinoma in situ of the cervix or uterus, ductal breast cancer in situ, resected non-metastatic breast or prostate cancer) within one year of screening. * Illicit drug abuse within 6 months of screening; * Heavy alcohol use (for men, 5 drinks or more on any day or 15 drinks or more per week; for women, 4 drinks or more on any day or 8 drinks or more per week); * Participation in another interventional clinical research study within 30 days of screening; * Breastfeeding, pregnancy, or unwillingness to be on contraception during the trial; * Presence of a clinically significant medical history, physical examination, or laboratory finding that may interfere with any aspect of study conduct or interpretation of results; * Any condition that may render the patient unable to comply with study requirements and/or complete the study.
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What it tests

  • Sotagliflozin
  • Placebo
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Where

19 sites
Stanford University Medical Center
Stanford, United States
Barbara Davis Center / University of Colorado Denver
Aurora, United States
AdventHealth
Orlando, United States
Northwestern University Feinberg School of Medicine
Chicago, United States
Joslin Diabetes Center
Boston, United States
Washington University
St Louis, United States
SUNY Upstate Medical University
Syracuse, United States
Albert Einstein College of Medicine / Montefiore Medical Center
The Bronx, United States

…and 11 more on ClinicalTrials.gov.

🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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