Chronic Kidney Disease, Chronic Kidney Disease (CKD) With Diabetes Mellitus (DM), Diabetic Ketoacidosis, Ketones, Type 1 Diabetes Mellitus
Conditions
Keywords
Type 1 Diabetes, Chronic Kidney Disease, Continuous Glucose Monitoring, Diabetic Ketoacidosis, Continuous Ketone Monitoring
Brief summary
The goal of this clinical trial is to develop and evaluate a novel diabetes ketoacidosis risk mitigation strategy to support the safe use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) therapy in participants with type 1 diabetes (T1D) and mild to moderate chronic kidney disease (CKD). The main objectives of this study are to: 1. Evaluate how ketone metrics differ between participants no chronic kidney disease (CKD), moderate risk CKD and high or very high-risk CKD in three time periods. 2. Identify potentially modifiable ketosis risk factors. 3. Use continuous dual ketone and glucose monitoring (DGK) data prior to and following treatment to determine ketosis risk factors and gain knowledge to further refine reporting of risk factors and determine which factors in the Ketone Action Plan (KAP) were most valuable. 4. Gather information on how participants and clinicians like and use the DGK reports. Participants will be asked to: * Meet with study investigators to determine if they are eligible * Sign written informed consent * Take a pregnancy test, if applicable * Have blood taken to assess kidney function and hemoglobin A1c * Take the study medication, following the study team instructions * Wear the study provided sensor throughout participation. * Complete 5 in person visits, and 11 phone check ins over a nine-month period * Provide feedback on their experience, usefulness of CGM/CKM reports, and the most valuable factors of the Ketone Action Plan (KAP).
Detailed description
Sodium-glucose cotransporter 2 (SGLT2) inhibitors and similar medications can prevent progression of heart and kidney disease but strategies to safely use these medications in people with type 1 diabetes (T1D) have not yet been developed. We will conduct an open-label trial of sotagliflozin (an SGLT 1/2 inhibitor) in 80 people with T1D with no chronic kidney disease (CKD), moderate risk CKD and high or very high risk CKD. Through the use of continuous ketone monitoring, we will characterize ketone levels in both individuals with chronic kidney disease (CKD) and T1D, compared to those with T1D without CKD, before and after starting sotagliflozin. We will improve our understanding of the risk factors for developing elevated ketone levels and optimize prevention of diabetes ketoacidosis through the development and refinement of an enhanced combined continuous glucose and ketone monitoring data visualization report.
Interventions
DRUGSotagliflozin initiation
All patients will be started on sotagliflozin at a dose of 200mg/d. After 3 months of sotagliflozin 200 mg/d, patients who do not achieve good glycemic control (TIR \>60%) and who have moderate or no CKD (eGFR \>60) will be offered the option to increase sotagliflozin to 400mg/d. The decision to increase sotagliflozin dose will be a shared decision between the study subject and the study investigators. All other participants will continue taking 200 mg sotagliflozin daily. After completing all study visits, all participants will stop taking sotagliflozin and continue care with their healthcare provider(s).
Sponsors
HealthPartners Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study intervention is an open label trial of 80 individuals with type 1 diabetes all wearing a continuous DGK sensor, divided into 3 cohorts based on renal function (no chronic kidney disease (CKD), moderate risk CKD and high or very high-risk CKD). All 80 participants will be evaluated for glucose control (CGM metrics and HbA1c) and ketone levels (continuous ketone sensor) over 3 study periods, each 3 months long. Period one - no study drug, blinded DGK sensor, period 2 on low starting dose of study drug, 200 mg sotagliflozin, and period 3 on either high dose of study drug, 400 mg sotagliflozin, or continuing low dose study drug). Study drug is oral sotagliflozin, 200 mg or 400 mg once daily. Study visits will be conducted in person at a dedicated study clinical research unit.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of signed and dated informed consent form. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Males and females; Ages 18-75. 4. Diagnosis of type 1 diabetes, based on a clinical diagnosis with onset at least 3 months prior to screening. 5. Using an automated insulin delivery system (AID) or multiple daily injections (MDI), (defined by use of rapid analogue with meals and approved long-acting analogue (e.g. detemir or glargine)). 6. Most recent eGFR ≥25 (and within prior 12 months). 7. HbA1c 7-\<-9%. 8. Have never used SGLT2i medications. 9. Must be willing and able to wear a DGK device and willing to follow the study protocol. 10. Must be able to read and speak English. 11. Use of adequate contraception for the duration of the study be the women of childbearing potential. 12. Access to necessary resources for participating in a technology-based intervention (i.e., computer, smartphone, internet access).
Exclusion criteria
1. Pregnant, lactating, or planning to become pregnant or unwillingness to be on contraception during the trial. 2. Any form of diabetes other than T1D. 3. Any history of use of sodium-glucose cotransporter inhibitors and use of other non-insulin glucose lowering medication within the last 6 months. 4. Chronic systemic corticosteroids (\>4 consecutive weeks) within 6 months before screening or planned use during the study period. 5. History of diabetic ketoacidosis within 3 months of screening or 2 or more episodes of DKA within the last year. 6. History of multiple (≥ 3 infections) genital mycotic or bacterial infections within 6 months of screening or any history of necrotizing fasciitis. 7. Hypotension at screening as defined as, systolic blood pressure \< 90 and diastolic blood pressure \< 60 with symptoms of low blood pressure (confusion, dizziness, lightheadedness, fainting, heart palpitations). 8. History of a level 3 hypoglycemic event (as defined by ADA criteria) within 3 months of screening. 9. Recent myocardial infarction, stroke, hospitalization for unstable angina or heart failure within 3 months prior to screening. 10. New York Heart Association Class IV heart failure. 11. CKD-EPI estimated glomerular filtration rate (eGFR) \<25 mL/min/1.73m2. 12. Impairment of systems and organs that may increase their risk of participating in the intervention study or compromise the results (for example: end stage kidney disease, active liver dysfunction, gastroparesis, anemia, organ transplant). 13. Active Hepatitis B or C, or tuberculosis. 14. Abnormal liver function at screening defined as any of the following: aspartate aminotransferase (AST) \>2X upper limit of the normal reference range (ULN), ALT \>2X ULN, serum total bilirubin (TB) \>1.5X ULN. 15. History of severe acquired immune deficiency syndrome or human immunodeficiency virus (HIV) infection or severely immunocompromised status, in the opinion of the investigator, including, but not limited to patients who have undergone organ or bone marrow transplantation. HIV positive patients who are on stable immunosuppressive therapy and have undetectable viral load may be eligible for inclusion in the study, subject to the investigator's discretion. 16. Current or past history of decompensated cirrhosis (defined as variceal bleeding, ascites or hepatic encephalopathy), and/or known diagnosis of cirrhosis. 17. 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. 18. History of kidney transplant. 19. Chronic kidney disease (CKD) from a known cause other than T1D. 20. Current or clinically significant history of an eating disorder. 21. BMI \<22 at time of screening. 22. Adherence to a very low carbohydrate or ketogenic diet (\<100g carbohydrate /day) and unwilling to change during study participation. 23. History of foot amputation. 24. Non-healing wounds of extremities. 25. Documented medical adhesive allergy, as evaluated by investigator. 26. Inability to perform the study follow up or unwilling to wear the DGK device. 27. Heavy alcohol use (for men, ≥5 drinks on any day or ≥15 drinks per week; for women, ≥4 drinks on any day or ≥8 drinks per week) at screening, history of alcohol use disorder or binge drinking. 28. Participation in another treatment or intervention study within the past six weeks. 29. Any condition or factor that would compromise the participant's safety or conduct of the study (for example: cognitive impairment, bipolar disorder, or eating disorder) or any other reason the PI deems that the patient should not be included.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in time in ketone range >1.5/mmol/L | 3 months, 6 months, 9 months |
| Number of episodes of diabetic ketoacidosis (DKA) | 6 months, 9 months |
Secondary
| Measure | Time frame |
|---|---|
| Number of episodes (>=15 minutes) at >0.6 mmol/L | 6 months, 9 months |
| Number of prolonged episodes (>=2 hours) at >0.6 mmol/L | 6 months, 9 months |
| Change in time in ketone level >1.0/mmol/L | 3 months, 6 months, 9 months |
| Number of episodes (>=15 minutes) at >1.0 mmol/L | 6 months, 9 months |
| Change in mean ketone level | 3 months, 6 months, 9 months |
| Highest ketone level in time period | 6 months, 9 months |
| Number of severe hypoglycemia episodes | 3 months, 6 months |
| Number of episodes (>=15 minutes) at >1.5 mmol/L | 6 months, 9 months |
| Number of prolonged episodes (>=2 hours) at >1.5 mmol/L | 6 months, 9 months |
| Change in time in ketone level >3.0/mmol/L | 3 months, 6 months, 9 months |
| Number of episodes (>=15 minutes) at >3.0 mmol/L | 6 months, 9 months |
| Number of prolonged episodes (>=2 hours) at >3.0 mmol/L | 6 months, 9 months |
| Change in time in ketone level >2.5/mmol/L | 3 months, 6 months, 9 months |
| Number of episodes (>=15 minutes) at >2.5 mmol/L | 6 months, 9 months |
| Number of prolonged episodes (>=2 hours) at >2.5 mmol/L | 6 months, 9 months |
| Change in time in ketone level >2.0/mmol/L | 3 months, 6 months, 9 months |
| Number of episodes (>=15 minutes) at >2.0 mmol/L | 6 months, 9 months |
| Number of prolonged episodes (>=2 hours) at >1.0 mmol/L | 6 months, 9 months |
| Number of prolonged episodes (>=2 hours) at >2.0 mmol/L | 6 months, 9 months |
| Change in time in ketone level >0.6/mmol/L | 3 months, 6 months, 9 months |
Countries
United States
Contacts
CONTACTKelsea Forrester, Dietitian
CONTACTRebecca Passi
PRINCIPAL_INVESTIGATORRichard Bergenstal, MD
HealthPartners/Park Nicollet International Diabetes Center
Outcome results
None listed