Combination Adjunctive Therapy to Address Multiple Metabolic Imbalances in Type 1 Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Change in HbA1c
研究概览
简要总结
This is a single site, double-blind, placebo-controlled, crossover trial to quantify the effects of combination adjunctive therapy on glycemic control, ketogenesis during insulinopenia, insulin resistance, and diabetes burden and quality of life.
详细描述
This is a single site, double-blind, placebo-controlled, crossover trial to quantify the effects of combination adjunctive therapy on glycemic control, ketogenesis during insulinopenia, insulin resistance, and diabetes burden and quality of life.
Up to 22 adult participants with type 1 diabetes (T1D) will be enrolled with at least 16 participants completing the study in full. After screening, baseline data (A1c, CGM, ambulatory insulin dosing, ambulatory ketones [fasting and after infusion set change], and psychosocial questionnaires) will be collected and participants will complete an insulin withdrawal test (IWT) and a hyperinsulinemic-euglycemic clamp (HEC) with indirect calorimetry (IDC). Participants will then receive 12-week insulin-adjunctive treatments with both: (1) SGLTi (sotagliflozin 200 mg daily) + Placebo and (2) SGLTi + GRA (volagidemab 35 mg weekly), in a random-order, cross-over design with a 14-week washout period between treatment periods. Throughout the treatment periods subjects will be seen weekly in clinic for medication dosing (GRA or placebo) and download/review of CGM, insulin, and ketone data. At the end of each treatment period, the baseline studies will be repeated. Subjects will return for a safety follow up visit 6 weeks after the final GRA or placebo dose.
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
- Double (Participant, Investigator)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women between the ages of 18 and 70 years old, inclusive, at the time of screening;
- •Females of non-childbearing potential must be ≥ 1 year post-menopausal or documented as being surgically sterile. Females of childbearing potential must agree to use two methods of contraception during the entire study and for an additional 3 months after the end of dosing with the investigational product;
- •Male subjects must be willing to use clinically acceptable method of contraception during the entire study and for an additional 6 months after the end of the treatment period;
- •Diagnosed with Type 1 diabetes 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 continuous subcutaneous insulin infusion (CSII) via an insulin pump or hybrid closed loop system;
- •Currently using a Continuous Glucose Monitoring (CGM) system;
- •A1c > 7% and ≤ 10%
- •eGFR ≥ 60 mL/min/1.73m²;
- •Able to provide written informed consent approved by an Institutional Review Board (IRB).
排除标准
- •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;
- •History of pancreatitis, medullary thyroid carcinoma or liver disease;
- •Clinically significant diagnosis of anemia (Hemoglobin < 9 g/dl at screening);
- •Body Mass Index (BMI) < 18.5 kg/m2 and/or weight <50kg;
- •Body Mass Index (BMI) > 35 kg/m2
- •Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Donations of plasma, packed RBCs, platelets or quantities less than 500 mL are allowed at investigator discretion;
- •Current or recent (within 1 month of screening) use of diabetes medications other than insulin; (examples include GLP-1 RA, SGLT-2i, Pramlintide, Metformin);
- •Women who are pregnant or lactating/breastfeeding;
- •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
sotagliflozin 200 mg
Each participant will receive 12-week insulin-adjunctive treatment with both: (1) SGLTi (sotagliflozin 200 mg PO each day) + Placebo and (2) SGLTi + GRA (volagidemab 35 mg subcutaneously each week), in a random-order, cross-over design with a 14-week washout period between treatment periods.
Sotagliflozin is a dual sodium-glucose co-transporter-1 and sodium-glucose co-transporter-2 (SGLT1/2) inhibitor.
干预措施: Sotagliflozin (Drug)
volagidemab 35 mg
Each participant will receive 12-week insulin-adjunctive treatment with both: (1) SGLTi (sotagliflozin 200 mg PO each day) + Placebo and (2) SGLTi + GRA (volagidemab 35 mg subcutaneously each week), in a random-order, cross-over design with a 14-week washout period between treatment periods.
Volagidemab is a human monoclonal antibody glucagon receptor antagonist (GRA).
干预措施: Volagidemab (Drug)
Placebo
Each participant will receive 12-week insulin-adjunctive treatment with both: (1) SGLTi (sotagliflozin 200 mg PO each day) + Placebo and (2) SGLTi + GRA (volagidemab 35 mg subcutaneously each week), in a random-order, cross-over design with a 14-week washout period between treatment periods.
干预措施: Volagidemab (Drug)
结局指标
主要结局
Change in HbA1c
时间窗: 12 weeks
Quantify the effects of combination adjunctive therapy on glycemic control. Though it has limitations, the HbA1c remains the gold standard measurement of glycemic control in diabetes.
次要结局
- Change in percent time in range (70-180 mg/dl) by CGM(12 weeks)
- Change in subject self reported ambulatory insulin dosing(12 weeks)
研究者
Schafer Boeder
Assistant Professor of Medicine
University of California, San Diego