Triple Therapy for Type 1 Diabetes With Insulin, Semaglutide, and Dapagliflozin
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 78
- 试验地点
- 2
- 主要终点
- Change in HbA1c following dapagliflozin
研究概览
简要总结
To assess whether the addition of dapagliflozin to semaglutide and insulin (triple therapy) improves glycemic control in patients with type 1 diabetes compared with semaglutide and insulin (dual therapy) and insulin only (standard) treatment.
详细描述
This will be a 52 week study for type 1 diabetics looking into the effect of semaglutide and dapagliflozin on HbA1c and glycemic control.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This will be a two-center, randomized, open-label then double-blind, parallel group, placebo and standard of care controlled prospective study in type 1 diabetes.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 Diabetes for at least 1 year on staple use of continuous subcutaneous insulin infusion (CSII) or multiple daily (four or more) injections (MDI) of insulin for last 3 months.
- •C-peptide <0.23 nM
- •Minimum dose of insulin in Units/kg at entry: 0.5 U/kg for MDI and 0.4 U/kg for CSII
- •Regularly measuring blood sugars four or more times daily.
- •HbA1c of >7.5%.
- •Well versed in CHO counting*
- •Age 18-70 years.
- •BMI ≥25 kg/m2.
排除标准
- •Type 1 diabetes for less than 12 months, type 2 diabetes, chronic pancreatitis, MODY
- •Previous use of any agent other than insulin for treatment of diabetes in the last 3 months.
- •History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 3 month prior to the screening visit
- •Frequent episodes of severe hypoglycemia as defined by more than one episode requiring medical assistance, emergency care (paramedics or emergency room care), and/or glucagon therapy administered by a third-party individual within 1 month prior to the screening visit
- •Symptoms of poorly controlled diabetes that would preclude participation in this trial
- •Subjects on a commercial weight loss program with ongoing weight loss, or on an intensive exercise program
- •History of bariatric surgery or lap-band procedure within 12 months prior to screening
- •History of Addison's disease or chronic adrenal insufficiency
- •History of diabetes insipidus
- •Hepatic disease or cirrhosis with Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN) and/or Alanine aminotransferase (ALT) > 3X ULN
- •Serum Total Bilirubin > 2X ULN unless exclusively caused by Gilbert's Syndrome
- •Hemoglobin < 11.0 g/dL (110 g/L) for men; hemoglobin < 10.0 g/dL (100 g/L) for women.
- •Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 3 months or patients with congestive heart failure.
- •ESRD on hemodialysis; and or e-GFR < 60 ml/min/1.73m2
- •HIV or Hepatitis B/C positive status
- •Any other life-threatening, noncardiac disease
- •History of pancreatitis
- •Women who are pregnant or women of childbearing potential who are not using adequate contraception or who are breast feeding
- •Inability to give informed consent
- •History of gastroparesis
- •History of medullary thyroid carcinoma or MEN 2 syndrome
- •History of serious hypersensitivity reaction to these agents
- •Painful gallstones
- •Hypertriglyceridemia (>500 mg/dl)
- •Recurrent genital mycotic infection.
- •Hypovolemic patients or with chronic renal insufficiency.
- •Patients with any malignancy except treated in situ malignancy and basal cell carcinoma of the skin
- •Unexplained hematuria
- •Patients with a history of diabetic retinopathy
- •Use of an investigational agent or therapeutic regimen within 30 days of study
- •Participation in any other concurrent interventional clinical trial
研究组 & 干预措施
Control
Standard of care insulin will be used as an active comparator arm for 1/3 of patients (38 patients) for the entire duration of the study.
干预措施: Insulin (Drug)
Dual Therapy
Once a week injection of Semaglutide (a GLP-1 receptor agonist) in addition to standard of care insulin for the first six months in 2/3 of patients (76 patients). Semaglutide is a clear, colorless solution that contains 2 mg of semaglutide in a 1.5 mL (1.34 mg/mL) pre-filled, disposable, single-patient-use pen injector. Semaglutide will be started at the 0.25 mg dose for the first two weeks, then increased to 0.5 mg at week 2, and then yet again increased to 1.0 mg at week 4.
干预措施: Semaglutide (Drug)
Triple therapy
Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of Dapagliflozin (an SGLT-2 inhibitor) added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)). Dapagliflozin will be started at 5 mg for one week, and then increased to 10 mg for the remainder of the study
干预措施: Insulin (Drug)
Triple therapy
Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of Dapagliflozin (an SGLT-2 inhibitor) added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)). Dapagliflozin will be started at 5 mg for one week, and then increased to 10 mg for the remainder of the study
干预措施: Semaglutide (Drug)
Triple therapy
Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of Dapagliflozin (an SGLT-2 inhibitor) added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)). Dapagliflozin will be started at 5 mg for one week, and then increased to 10 mg for the remainder of the study
干预措施: Dapagliflozin (Drug)
Triple therapy control
Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of the Placebo form of Dapagliflozin added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)).
干预措施: Semaglutide (Drug)
Dual Therapy
Once a week injection of Semaglutide (a GLP-1 receptor agonist) in addition to standard of care insulin for the first six months in 2/3 of patients (76 patients). Semaglutide is a clear, colorless solution that contains 2 mg of semaglutide in a 1.5 mL (1.34 mg/mL) pre-filled, disposable, single-patient-use pen injector. Semaglutide will be started at the 0.25 mg dose for the first two weeks, then increased to 0.5 mg at week 2, and then yet again increased to 1.0 mg at week 4.
干预措施: Insulin (Drug)
Triple therapy control
Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of the Placebo form of Dapagliflozin added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)).
干预措施: Insulin (Drug)
Triple therapy control
Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of the Placebo form of Dapagliflozin added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)).
干预措施: Placebo to Dapagliflozin (Drug)
结局指标
主要结局
Change in HbA1c following dapagliflozin
时间窗: 6 months
Change in HbA1c at 6 months following dapagliflozin or placebo therapy in addition to combined semaglutide and insulin treatment.
次要结局
- body weight assessment following triple therapy(12 months)
- Urinary ketones assessment(12 months)
- Blood pressure medication use(12 months)
- Change in HbA1c with semaglutide(6 months)
- Assessment of hypoglycemia(12 months)
- Fructosamine indices(12 months)
- Insulin requirement indices(12 months)
- Severe (level 3) hypoglycemia assessment(12 months)
- Weekly fasting glucose indices(12 months)
- Systolic Blood pressure assessment after triple therapy(12 months)
- Assessment of hyperglycemia level 1(12 months)
- Assessment of hyperglycemia level 2(12 months)
- Assessment of percent time glucose in range(12 months)
- body weight assessment following dapagliflozin(6 months)
- body weight assessment following semaglutide(6 months)
- Level 1 hyperglycemia assessment(12 months)
- serum ketones assessment(12 months)
- Diabetic ketoacidosis assessment(12 months)
- Change in HbA1c with triple therapy(12 months)
- Diastolic Blood pressure assessment(12 months)
- Level 2 hypoglycemia assessment(12 months)
- Level 2 hyperglycemia assessment(12 months)
研究者
paresh Dandona
SUNY Distinguished Professor, Head of Endocrinology, Diabetes, and Metabolism, State University of New York
State University of New York at Buffalo