A Pilot Trial of Adding Oral Hypoglycemic Therapy to Insulin Treatment in Monogenic Variant Carriers of the Joslin 50-Year Medalist Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Glycated hemoglobin (HbA1c)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of adding oral hypoglycemic agents (OHA) to existing insulin treatment in monogenic variant carriers of the Joslin 50-Year Medalist Study ("Medalists"), who are characterized by ≥50 years of insulin-dependent diabetes. Our primary objective is to evaluate whether the presence of human leukocyte antigen (HLA) high-risk alleles for diabetes (DR3 and/or DR4) can affect the effectiveness of OHA in these subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 85 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Existing participants in the Joslin 50-Year Medalist Study
- •Residing in the United States
- •Capable of giving informed consent
- •Known detectable C-peptide >0.05 ng/mL
排除标准
- •Known diagnosis of cancer or active inflammatory disease such as rheumatoid arthritis, lupus, and inflammatory bowel disease
- •Recent history of myocardial infarction, angioplasty, bypass surgery, heart failure, angina, stroke, or uncontrolled hypertension>160/100 during the past 3 months
- •Known diagnosis of cognitive dysfunction, dementia or Alzheimer's disease
- •Pre-existing liver disease or liver function tests (AST or ALT)>3x the upper limit of normal
- •Pre-existing kidney disease (Chronic Kidney Disease Stage IV and below, or estimated glomerular filtration rate<45 mL/min/1.73 m2)
- •Active use of immunosuppressants
- •Recipients of prior islet cell or pancreas transplantation
- •Inability to travel due to frailty or health reasons
- •Donated blood within the previous two (2) months
研究组 & 干预措施
HLA+ Group
Participants who are high-risk HLA-DR3 and/or DR4 (+); monogenic variant (+) with rare exome variant ensemble learner (REVEL) score>0.75; and both glutamic acid decarboxylase (GAD65) and islet antigen (IA2) autoantibody (-)
干预措施: Metformin Extended Release Oral Tablet (Drug)
HLA+ Group
Participants who are high-risk HLA-DR3 and/or DR4 (+); monogenic variant (+) with rare exome variant ensemble learner (REVEL) score>0.75; and both glutamic acid decarboxylase (GAD65) and islet antigen (IA2) autoantibody (-)
干预措施: Sitagliptin (Drug)
HLA- Group
Participants who are high-risk HLA-DR3 and DR4 (-); with known or yet unknown monogenic variants with REVEL score>0.75; and either GAD65 and IA2 autoantibody (-), or autoantibody (+) with titers close to the cutoff
干预措施: Metformin Extended Release Oral Tablet (Drug)
HLA- Group
Participants who are high-risk HLA-DR3 and DR4 (-); with known or yet unknown monogenic variants with REVEL score>0.75; and either GAD65 and IA2 autoantibody (-), or autoantibody (+) with titers close to the cutoff
干预措施: Sitagliptin (Drug)
结局指标
主要结局
Glycated hemoglobin (HbA1c)
时间窗: 3 months and 6 months
Change in HbA1c (%) between the two study groups
次要结局
- Daily insulin dose(3 months and 6 months)
- Total cholesterol(3 months and 6 months)
- Triglycerides(3 months and 6 months)
- Area under the plasma concentration versus time curve (AUC) of C-peptide(6 months)
- Body mass index (BMI)(3 months and 6 months)
- High density lipoprotein (HDL)-cholesterol(3 months and 6 months)
- C-peptide(3 months and 6 months)
- Low density lipoprotein (LDL)-cholesterol(3 months and 6 months)