Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes: a Randomized, Placebo-controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Number of symptomatic hypoglycemia
研究概览
简要总结
This study is to analyze whether the SGLT2-inhibitor empagliflozin or the IL-1 receptor antagonist anakinra may improve postprandial hypoglycemia in subjects with prediabetes.
详细描述
Subjects with prediabetes may develop postprandial hypoglycemia. This is probably due to a dysfunction of the insulin producing β-cell characterized by a delayed and exaggerated insulin secretion leading to an initial peak in glycaemia followed by a rapid fall and eventually resulting in hypoglycemia. The latter occurring typically within 1 to 3 hours after food intake.
In patients with gastric bypass surgery and postprandial hypoglycemia the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra reduced postprandial insulin release and prevented hypoglycemia. This study is to analyze whether a similar therapeutic approach using empagliflozin and anakinra may also improve postprandial hypoglycemia in subjects with prediabetes.
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)
盲法说明
Participants, investigators and study nurses will be blinded to the study drug.
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
- •Subjects with prediabetes defined by Glycosylated haemoglobin A1c (HbA1c) 5.7-6.4 % or fasting plasma glucose 6.1-6.9 mmol/l) or plasma glucose 2 h following 75 glucose ingestion of 7.8-11.0 mmol/l.
- •Hypoglycemia occuring 1 to 3 h following ingestion of a standardized liquid mixed-meal (75 g carbohydrates) and fulfilling the Whipple's triad (glucose below 3.0 mmol/l).
- •Age ≥ 18 years
- •For subjects with reproductive potential, willingness to use contraceptive measures adequate to prevent the subject from becoming pregnant during the study
排除标准
- •Upper gastrointestinal surgery
- •Diagnosis of any type of diabetes mellitus
- •Signs of current infection
- •Use of investigational drug up to one week prior to start of treatment phase
- •Glucocorticoid therapy
- •Neutropenia (leukocyte count < 1.5 × 109/L or absolute neutrophil count (ANC) < 0.5 × 109/L)
- •Anemia (hemoglobin < 11 g/dL for males, < 10 g/dL for females)
- •Clinically significant kidney or liver disease (creatinine > 1.5 mg/dL, aspartate aminotransferase (AST)/ALT > 2 × ULN, alkaline phosphatase > 2 × ULN, or total bilirubin [tBili] > 1.5 × ULN)
- •Uncontrolled disease
- •Currently pregnant or breastfeeding
- •No subjects meeting the criteria for vulnerability
- •Participation in another study with investigational drug within the 30 days preceding and during the present study.
研究组 & 干预措施
Group 1 (anakinra; placebo; empagliflozin)
Group 1:
study day 1: anakinra; study day2: placebo; study day 3: empagliflozin
干预措施: empagliflozin (Drug)
Group 1 (anakinra; placebo; empagliflozin)
Group 1:
study day 1: anakinra; study day2: placebo; study day 3: empagliflozin
干预措施: anakinra (Drug)
Group 1 (anakinra; placebo; empagliflozin)
Group 1:
study day 1: anakinra; study day2: placebo; study day 3: empagliflozin
干预措施: saline subcutaneous (s.c.) (placebo) (Other)
Group 1 (anakinra; placebo; empagliflozin)
Group 1:
study day 1: anakinra; study day2: placebo; study day 3: empagliflozin
干预措施: tablet per oral (p.o.) (placebo) (Other)
Group 2 (placebo; anakinra; empagliflozin)
study day 1: placebo; study day2: anakinra; study day 3: empagliflozin
干预措施: empagliflozin (Drug)
Group 2 (placebo; anakinra; empagliflozin)
study day 1: placebo; study day2: anakinra; study day 3: empagliflozin
干预措施: anakinra (Drug)
Group 2 (placebo; anakinra; empagliflozin)
study day 1: placebo; study day2: anakinra; study day 3: empagliflozin
干预措施: saline subcutaneous (s.c.) (placebo) (Other)
Group 2 (placebo; anakinra; empagliflozin)
study day 1: placebo; study day2: anakinra; study day 3: empagliflozin
干预措施: tablet per oral (p.o.) (placebo) (Other)
Group 3 (empagliflozin; placebo; anakinra)
study day 1: empagliflozin; study day2: placebo; study day 3: anakinra
干预措施: empagliflozin (Drug)
Group 3 (empagliflozin; placebo; anakinra)
study day 1: empagliflozin; study day2: placebo; study day 3: anakinra
干预措施: anakinra (Drug)
Group 3 (empagliflozin; placebo; anakinra)
study day 1: empagliflozin; study day2: placebo; study day 3: anakinra
干预措施: saline subcutaneous (s.c.) (placebo) (Other)
Group 3 (empagliflozin; placebo; anakinra)
study day 1: empagliflozin; study day2: placebo; study day 3: anakinra
干预措施: tablet per oral (p.o.) (placebo) (Other)
Group 4 (empagliflozin; anakinra; placebo)
study day 1: empagliflozin; study day2: anakinra; study day 3: placebo
干预措施: empagliflozin (Drug)
Group 4 (empagliflozin; anakinra; placebo)
study day 1: empagliflozin; study day2: anakinra; study day 3: placebo
干预措施: anakinra (Drug)
Group 4 (empagliflozin; anakinra; placebo)
study day 1: empagliflozin; study day2: anakinra; study day 3: placebo
干预措施: saline subcutaneous (s.c.) (placebo) (Other)
Group 4 (empagliflozin; anakinra; placebo)
study day 1: empagliflozin; study day2: anakinra; study day 3: placebo
干预措施: tablet per oral (p.o.) (placebo) (Other)
Group 5 (placebo; empagliflozin; anakinra)
study day 1: placebo; study day2: empagliflozin; study day 3: anakinra
干预措施: empagliflozin (Drug)
Group 6 (anakinra; empagliflozin; placebo)
study day 1:anakinra; study day2: empagliflozin; study day 3: placebo
干预措施: saline subcutaneous (s.c.) (placebo) (Other)
Group 5 (placebo; empagliflozin; anakinra)
study day 1: placebo; study day2: empagliflozin; study day 3: anakinra
干预措施: anakinra (Drug)
Group 5 (placebo; empagliflozin; anakinra)
study day 1: placebo; study day2: empagliflozin; study day 3: anakinra
干预措施: saline subcutaneous (s.c.) (placebo) (Other)
Group 5 (placebo; empagliflozin; anakinra)
study day 1: placebo; study day2: empagliflozin; study day 3: anakinra
干预措施: tablet per oral (p.o.) (placebo) (Other)
Group 6 (anakinra; empagliflozin; placebo)
study day 1:anakinra; study day2: empagliflozin; study day 3: placebo
干预措施: empagliflozin (Drug)
Group 6 (anakinra; empagliflozin; placebo)
study day 1:anakinra; study day2: empagliflozin; study day 3: placebo
干预措施: anakinra (Drug)
Group 6 (anakinra; empagliflozin; placebo)
study day 1:anakinra; study day2: empagliflozin; study day 3: placebo
干预措施: tablet per oral (p.o.) (placebo) (Other)
结局指标
主要结局
Number of symptomatic hypoglycemia
时间窗: up to 3 hours after ingestion of the liquid mixed-meal
Incidence of symptomatic hypoglycemia following a standardized mixed-meal test defined by appearance of typical symptoms, blood glucose level below 3.0 mmol/l and relief of symptoms when the glucose level is raised (Whipple's triad).
次要结局
- Nadir plasma glucose (mmol/l)(up to 3 hours after ingestion of the liquid mixed-meal)
- Change in inflammatory state(at baseline and 60 min after ingestion of the mixed meal)
- Change in RNA sequencing (RNAseq) in peripheral PBMC(at baseline and 60 min after ingestion of the mixed meal)
- Change in proinsulin to insulin ratio in serum(at baseline and 60 min after ingestion of the mixed meal)
- Severity of symptoms of hypoglycemia according to the Edinburgh Hypoglycemia Scale(up to 3 hours after ingestion of the liquid mixed-meal)