Utilizing Continuous Ketone Monitors to Enable Safe Use of SGLT Inhibitors in Patients With Type 1 Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- BHB Time Above 0.6mmol/L - 200mg
研究概览
简要总结
This research study is being conducted to learn if wearing a combination continuous glucose monitor/continuous ketone monitor (CGM/CKM) can reduce the side effects of taking sotagliflozin (study drug) in people with type 1 diabetes.
详细描述
The study is a phase 3, single-site, double-blind, random-order, cross-over study to evaluate the use of continuous ketone monitoring (CKM) in participants with type 1 diabetes taking sotagliflozin.
There will be 2 main groups in the study, participants on Hybrid Closed Loop insulin pumps (HCL), n=26, and participants on Multiple Daily Injections (MDI), n=26. There will also be 2 doses of sotagliflozin examined in the study, 200 milligram (mg) once daily and 400mg once daily. Therefore, there will be 4 treatment groups in the study:
- MDI participants who receive 200mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 400mg sotagliflozin for 6 weeks;
- MDI participants who receive 400mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 200mg sotagliflozin for 6 weeks;
- HCL participants who receive 200mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 400mg sotagliflozin for 6 weeks;
- HCL participants who receive 400mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 200mg sotagliflozin for 6 weeks.
In addition, there will be an open-label extension study for the HCL group. In the extension study, the 26 participants in the HCL group will remain on their insulin pump, receive a low-dose, open-label, once daily injection of long-acting insulin and complete an additional 6 weeks of dosing with open-label 400 mg sotagliflozin.
For MDI participants there will be a total of 12 visits over approximately 22 weeks. For HCL participants there will be a total of 16 visits over approximately 28 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All individuals between the ages of >18 years old, inclusive, at the time of screening;
- •Individuals able to become pregnant must:
- •be ≥1 year post-menopausal or documented as being surgically sterile, or
- •agree to use two methods of contraception during the entire study and for an additional 2 weeks after the end of dosing with the investigational product;
- •Individuals able to cause a pregnancy must be willing to use clinically acceptable method of contraception during the entire study and for an additional 2 weeks after the end of the treatment period;
- •Diagnosed with Type 1 diabetes ≥ 1 year prior to screening, based on clinical history or as defined by the current American Diabetes Association (ADA) criteria;
- •Treatment with a stable insulin regimen for at least 8 weeks before screening with:
- •a continuous subcutaneous insulin infusion (CSII) via a hybrid closed loop system, or
- •multiple daily insulin injections;
- •Currently using a Continuous Glucose Monitoring (CGM) system;
- •Hemoglobin A1c ≤10% at the time of screening;
- •Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2;
- •Agrees and is able to wear the investigational device;
- •Able to provide written informed consent approved by an Institutional Review Board (IRB).
排除标准
- •Individuals who are currently pregnant or lactating/breastfeeding, or planning to become pregnant within 10 months after screening;
- •Any concurrent diagnosis of diabetes other than type 1 diabetes;
- •History or evidence of clinically significant disorder or condition that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;
- •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);
- •Current or recent (within 1 month prior to screening) use of diabetes medications other than insulin; (examples include, Sodium-Glucose Cotransporter 2 (SGLT-2i), Pramlintide, Metformin);
- •Use of glucagon-like-peptide 1 (GLP-1) analogues if not on a stable dose for > 2 months at screening (participants can be rescreened after being on stable dose for > 2 months). Participants on a stable dose of GLP-1 receptor antagonist (RA) and not experiencing frequent vomiting may be included.
- •Chronic systemic corticosteroids use ( > 4 consecutive weeks) within 6 months prior to screening;
- •History of diabetic ketoacidosis within 3 months prior screening;
- •History of a level 3 hypoglycemic event (as defined by ADA criteria) within 3 months of screening.
- •ADA Level 3 Definition - A severe hypoglycemic event characterized by altered mental or physical status requiring the assistance for treatment of hypoglycemia, irrespective of glucose level;
- •History of multiple (≥3 infections) genital mycotic infections within 6 months of screening;
- •Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits;
- •Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent.
研究组 & 干预措施
Treatment Group A
200mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 400mg sotagliflozin for 6 weeks
干预措施: Sotagliflozin Low Dose (Drug)
Treatment Group A
200mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 400mg sotagliflozin for 6 weeks
干预措施: Sotagliflozin High Dose (Drug)
Treatment Group A
200mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 400mg sotagliflozin for 6 weeks
干预措施: Dual Continuous Glucose and Ketone Monitor (Device)
Treatment Group B
400mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 200mg sotagliflozin for 6 weeks
干预措施: Sotagliflozin Low Dose (Drug)
Treatment Group B
400mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 200mg sotagliflozin for 6 weeks
干预措施: Sotagliflozin High Dose (Drug)
Treatment Group B
400mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 200mg sotagliflozin for 6 weeks
干预措施: Dual Continuous Glucose and Ketone Monitor (Device)
结局指标
主要结局
BHB Time Above 0.6mmol/L - 200mg
时间窗: 6 weeks
Beta hydroxybutyrate (BHB) time \> 0.6 millimole per liter (mmol/L) as measured by the DGK during the 200mg dosing period in the MDI vs. HCL groups.
BHB Time Above 0.6mmol/L - 400mg
时间窗: 6 weeks
Beta hydroxybutyrate (BHB) time \> 0.6 mmol/L as measured by the DGK during the 400mg dosing period in the MDI vs. HCL groups.
次要结局
- BHB Time Above 0.6mmol/L - 200mg vs. 400mg(6 weeks)
研究者
Jeremy Pettus, MD
Associate Professor
University of California, San Diego