Closed-Loop Glucagon Administration For The Automated Treatment Of Post-Bariatric Hypoglycemia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Area Over the Curve and <60 mg/dl (CGM) Measured in mg/dl *Min
研究概览
简要总结
This study is to test our automated hypoglycemia prevention and treatment device (glucagon-only bionic pancreas) in subjects that have undergone post-bariatric surgery that are experiencing symptoms of hypoglycemia.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Glucagon and placebo were blinded by the research pharmacy. Subjects were given bags of blinded medication labeled with which day they were to be used, and then were asked to label the bags with which day the medication was actually used. The contents of the bags were verified with the research pharmacy's blinding key upon completion of the study.
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 21 years or older with a gastric bypass for more than 1 year.
- •Post-bariatric hypoglycemia with prior episodes of neuroglycopenia, unresponsive to dietary intervention (low glycemic index, controlled carbohydrate portions) and trial of acarbose therapy at the maximally tolerated dose. Other therapies will not exclude a subject as long as the therapy is continued during the study.
- •Otherwise healthy (mild chronic disease such as asthma, hypertension, and depression will be allowed if well controlled).
- •Self-reported frequency of documented hypoglycemia (BG < 60 mg/dl verified by capillary blood glucose measurements) of at least 2 times per week.
排除标准
- •Unable to provide informed consent.
- •Unable to comply with study procedures.
- •Current participation in another hypoglycemia related clinical trial other than one that is primarily observational in nature.
- •Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception.
- •Use of insulin and/or insulin secretogues as sulfonylurea, metglitides, and glitazones.
- •History of cystic fibrosis, pancreatitis, type 1 diabetes or other pancreatic disease.
- •End stage renal disease on dialysis (hemodialysis or peritoneal dialysis).
- •Any known liver or biliary disease including cirrhosis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, any form of viral hepatitis.
- •Congestive heart failure (established history of CHF, paroxysmal nocturnal dyspnea, or orthopnea).
- •Acute illness or exacerbation of chronic illness at the time of the study.
- •Known insulinoma or predominantly fasting pattern of hypoglycemia
- •Adrenal insufficiency. Congenital hyperinsulinemia presenting with hypoglycemia during infancy.
- •History of pheochromocytoma. Fractionated metanephrines will be tested in patients with history increasing the risk for a catecholamine secreting tumor:
- •Paroxysms of tachycardia, pallor, or headache.
- •Personal or family history of MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau disease.
- •Episodic or treatment refractory (requiring 4 or more medications to achieve normotension) hypertension.
- •Untreated or inadequately treated mental illness (indicators would include symptoms such as psychosis, hallucinations, mania, and/or any psychiatric hospitalization in the last year).
- •Current alcohol abuse (intake averaging > 3 drinks daily in last 30 days) or substance abuse (any use within the last 6 months of controlled substances without a prescription).
- •Unwilling or unable to refrain from drinking more than two drinks in an hour or more than four drinks in a day during the trial.
- •Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference.
- •History of adverse reaction to glucagon (including allergy) besides nausea and vomiting.
- •Unwilling or unable to completely avoid acetaminophen during the study period.
- •Any factors that, in the opinion of the principal investigator, would interfere with the safe completion of the study procedures.
研究组 & 干预措施
Glucagon-only bionic pancreas - glucagon
Subjects will wear the bionic pancreas that consists of a continuous glucose monitor linked to a smartphone running a hypoglycemia prevention algorithm that doses glucagon from an insulin pump through a subcutaneous infusion set.
Subjects will continue to manage any hypoglycemia that occurs according to the current recommendations of their care provider.
干预措施: Glucagon-only bionic pancreas - glucagon (Device)
Glucagon-only bionic pancreas - placebo
Subjects will wear the bionic pancreas that consists of a continuous glucose monitor linked to a smartphone running a hypoglycemia prevention algorithm that doses placebo from an insulin pump through a subcutaneous infusion set.
Subjects will continue to manage any hypoglycemia that occurs according to the current recommendations of their care provider.
干预措施: Glucagon-only bionic pancreas - placebo (Device)
结局指标
主要结局
Area Over the Curve and <60 mg/dl (CGM) Measured in mg/dl *Min
时间窗: 14 days
The measure for area over the curve is used when an integrated assessment (e.g., a measurement of something over a specific amount of time) is more useful in understanding a phenomenon. To calculate this measure, a method of approximation is often used. One way would be to estimate the curve via curve-fitting techniques. For this outcome, using area over the curve and \<60mg/dl provides a more robust method of calculating amount of hypoglycemia (by including more severe degrees of hypoglycemia in the product of mg/dl\*min as opposed to percentage of time below 60mg/dl.
次要结局
- Percentage of Time Spent Within the Glucose Range 70-120 mg/dl(14 days)
- Percentage of Time Spent Within the Glucose Range 70-180 mg/dl(14 days)
- Percentage of Time Spent Within the Glucose Range >180 mg/dl(14 days)
- Number of Carbohydrate Interventions for Hypoglycemia Per Day(14 days)
- Percentage of Time With CGM Glucose Less Than 60 mg/dl During Daytime ( 7:00 AM-11:00 PM)(14 days)
- Percentage of Time With CGM Glucose Less Than 60 mg/dl Overnight (11:00 PM - 7:00 AM)(14 days)
- Total Number of Grams of Carbohydrate Taken for Hypoglycemia Per Day(14 days)
- Number of Symptomatic Hypoglycemia Events Per Day(14 days)
- Number of Days With Nausea(14 days)
- Severity of Nausea on Daily E-mail Survey(14 days)
- Mean Continuous Glucose Monitor (CGM) Glucose(2 weeks)
- Fraction of Time Spent Within the Glucose Range >250 mg/dl(2 weeks)
- Mean Absolute Relative Deviation (MARD) of CGM vs. All StatStrip Xpress BG Measurements(14 days)
- Total Glucagon Dosing (mcg/kg/24 Hours)(2 weeks)
- Percentage of Days When Participants Correctly Guessed Intervention (Glucagon vs Placebo) Out of a Total of 14 Days.(2 weeks)
研究者
Steven J. Russell, MD, PhD
Assistant Professor of Medicine
Massachusetts General Hospital