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临床试验/NCT02527993
NCT02527993已完成4 期

Treatment of Hypoglycemia Following Gastric Bypass Surgery

Zealand University Hospital0 个研究点目标入组 11 人开始时间: 2015年10月最近更新:
适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
已完成
入组人数
11
主要终点
Changes in blood glucose (mmol/L) assessed by continuous glucose monitoring (CGM).

研究概览

简要总结

Obesity is increasing worldwide and consequently the need for efficient treatment opportunities. Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed bariatric procedures used in the treatment of severe obesity. The surgery results in significant and sustained weight loss and has a beneficial effect on blood glucose regulation.

However, some patients experience the syndrome postprandial hyperinsulinemic hypoglycemia years after the operation, with symptoms varying from mild dizziness to confusion, loss of consciousness and seizures. Larger insulin and glucagon-like peptide 1 (GLP-1) responses to an oral glucose load are believed to play a role in the syndrome, which is not yet fully understood. There are no current treatment guidelines beside dietary recommendations.

The purpose of this study is to compare different pharmacological treatments on daily blood glucose variations as well as postprandial hormonal and autonomous changes in subjects with symptoms of postprandial hyperinsulinemic hypoglycemia after RYGB.

详细描述

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed bariatric procedures used in the treatment of severe obesity. RYGB has in several studies been shown to result in significant and sustained weight loss. Moreover, RYGB has a beneficial effect on obese subjects with type 2 diabetes by improving blood glucose regulation, resulting in remission or partial remission of type 2 diabetes already days after surgery.

The changes of the anatomy of the stomach and small intestine cause a faster and more abrupt increase in blood glucose after a meal. As a consequence of the changed glucose absorption after RYGB and the increased insulin secretion, some subjects experience the condition named postprandial hyperinsulinemic hypoglycemia. Postprandial hyperinsulinemic hypoglycemia is typically seen years after RYGB and the symptoms vary from mild dizziness to confusion, loss of consciousness and seizures. The condition is characterized by large postprandial blood glucose variations accompanied by exaggerated insulin and glucagon-like peptide 1 (GLP-1) responses. Continuous glucose monitoring (CGM) have shown that subjects suffering from postprandial hyperinsulinemic hypoglycemia presents large variations in blood glucose from values below 3.5 mmol/L to diabetic values above 11.1 mmol/L within the first hour after a meal.

At present, there are no treatment guidelines beside dietary recommendations. Experimental treatment includes diet modifications, pharmaceutical treatments and surgical procedures. Several pharmaceutical agents have been attempted in the management of postprandial hyperinsulinemic hypoglycemia, but overall the existing studies consist of few case reports and case series evaluated primarily by relief of symptoms and not by CGM and hormonal analyses.

The study is designed as a randomized, non-blinded cross-over study including five treatment arms. The pharmaceutical agents are: a) Glucobay, b) Januvia, c) Verapamil, d) Victoza and e) Signifor. The treatment duration is 1 - 3 weeks, except for Signifor, which is administered for one day only. Each treatment period is separated by a wash out period of 7-10 days.

Sixteen none diabetic women are included in the study. They have undergone RYGB and have symptoms of postprandial hyperinsulinemic hypoglycemia. Moreover, former CGM has shown fluctuations in blood glucose of more than 5 mmol/L during daily living and with at least one blood glucose reading below 3.5 mmol/L.

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
None

入排标准

年龄范围
25 Years 至 60 Years(Adult)
性别
Female
接受健康志愿者

入选标准

  • symptoms of postprandial hyperinsulinemic hypoglycemia.
  • fluctuations in blood glucose of more than 5 mmol/L during daily living
  • at least one blood glucose reading below 3.5 mmol/L.
  • More than 18 months since RYGB
  • HbA1c < 40 mmol/L
  • Hemoglobin > 7,3 mmol/L
  • Ferritin > 30 µg/L
  • Cobalamin > 150 picomol/L
  • Creatinine < 105 mmol/L
  • C peptide > 1,0 nmol/L
  • Insulin > 35 pmol/L
  • Normal EKG
  • Negative human chorionic gonadotropin (hCG) urine test
  • Females of reproductive age: use of safe contraception

排除标准

  • Treatment for cardiovascular disease
  • Treatment with antipsychotics, antidepressants or anxiolytics
  • Treatment for thyroid disease
  • Prior medical treatment of postprandial hyperinsulinemic hypoglycemia
  • Allergy for the study medicine

研究组 & 干预措施

Glucobay

Experimental

Tablet Glucobay (acarbose) 50 mg x 6 daily for 7 days.

干预措施: Continuous glucose monitoring (CGM) (Device)

Glucobay

Experimental

Tablet Glucobay (acarbose) 50 mg x 6 daily for 7 days.

干预措施: Glucobay (acarbose) (Drug)

Glucobay

Experimental

Tablet Glucobay (acarbose) 50 mg x 6 daily for 7 days.

干预措施: Meal tolerance test (MTT) (Dietary Supplement)

Januvia

Experimental

Tablet Januvia (sitagliptin) 100 mg orally O.D for 7 days.

干预措施: Januvia (sitagliptin) (Drug)

Januvia

Experimental

Tablet Januvia (sitagliptin) 100 mg orally O.D for 7 days.

干预措施: Continuous glucose monitoring (CGM) (Device)

Januvia

Experimental

Tablet Januvia (sitagliptin) 100 mg orally O.D for 7 days.

干预措施: Meal tolerance test (MTT) (Dietary Supplement)

Verapamil

Experimental

Tablet Verapamil 120 mg orally O.D for 7 days.

干预措施: Verapamil HEXAL (verapamil) (Drug)

Verapamil

Experimental

Tablet Verapamil 120 mg orally O.D for 7 days.

干预措施: Continuous glucose monitoring (CGM) (Device)

Verapamil

Experimental

Tablet Verapamil 120 mg orally O.D for 7 days.

干预措施: Meal tolerance test (MTT) (Dietary Supplement)

Victoza

Experimental

Subcutaneous injection of Victoza (liraglutide) 0,6-1,2 mg O.D for three weeks.

干预措施: Victoza (liraglutide) (Drug)

Victoza

Experimental

Subcutaneous injection of Victoza (liraglutide) 0,6-1,2 mg O.D for three weeks.

干预措施: Continuous glucose monitoring (CGM) (Device)

Victoza

Experimental

Subcutaneous injection of Victoza (liraglutide) 0,6-1,2 mg O.D for three weeks.

干预措施: Meal tolerance test (MTT) (Dietary Supplement)

Signifor

Experimental

Subcutaneous injection of Signifor (pasireotide) 300 µg as a single dose prior to a meal tolerance test.

干预措施: Signifor (pasireotide) (Drug)

Signifor

Experimental

Subcutaneous injection of Signifor (pasireotide) 300 µg as a single dose prior to a meal tolerance test.

干预措施: Meal tolerance test (MTT) (Dietary Supplement)

结局指标

主要结局

Changes in blood glucose (mmol/L) assessed by continuous glucose monitoring (CGM).

时间窗: 6 days CGM will be performed at week 1, 3, 5, 7 and 11.

次要结局

  • Changes in glucose (mmol/L) in response to a meal tolerance test (MTT)(From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.)
  • Changes heart rate (beats/min) during the course of a meal tolerance test (MTT)(From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.)
  • Changes in insulin (pmol/L) in response to a meal tolerance test (MTT)(From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.)
  • Changes in Insulin-like growth factor 1 (nmol/L) in response to a meal tolerance test (MTT)(From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.)
  • Changes in glucagon (pmol/L) in response to a meal tolerance test (MTT)(From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.)
  • Changes in C-peptide (nmol/L) in response to a meal tolerance test (MTT)(From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.)
  • Changes in epinephrine (pmol/L) in response to a meal tolerance test (MTT)(From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.)
  • Changes in gastric inhibitory peptide (pmol/L) in response to a meal tolerance test (MTT)(From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.)
  • Changes in norepinephrine (pmol/L) in response to a meal tolerance test (MTT)(From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.)
  • Changes in glucagon-like peptide 1 (pmol/L) in response to a meal tolerance test (MTT)(From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Caroline Christfort Øhrstrøm

MD, clinical assistant

Zealand University Hospital

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