Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <65 mg/dL
研究概览
简要总结
To assess the efficacy of a closed loop glucagon system to prevent and treat hypoglycemia occurring in patients with Post-Bariatric Hypoglycemia (PBH) in response to meals and exercise.
详细描述
A control system for sensor-guided delivery was previously developed and tested in a Proof-of-Concept (POC) study in a clinical research setting during 9 mixed meal tolerance tests in 8 unique patients with severe hypoglycemia following bariatric surgery. This optimized algorithm will now be implemented to deliver stable glucagon in a closed-loop system.
A randomized, placebo-controlled, masked trial will be conducted to assess the efficacy of the closed loop system to prevent and treat hypoglycemia occurring in patients with PBH in response to meals (part 1). Part 2 will test whether the closed loop system can also prevent and treat hypoglycemia in patients with PBH in response to exercise. A manufacturing program from our collaborating team at Xeris Pharmaceuticals will continue to produce supplies of glucagon for the clinical trial in a current good manufacturing practice (cGMP) facility, with continued shelf-life stability testing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Study medication will be provided in vials which are labeled with randomization information only but not contents of vial.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females diagnosed with ongoing 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.
- •Age 18-65 years of age, inclusive, at screening.
- •Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits.
排除标准
- •Documented hypoglycemia occurring in the fasting state (> 12 hours fast);
- •Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
- •Hepatic disease, including serum alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0;
- •Congestive heart failure, New York Heart Association (NYHA )class II, III or IV;
- •History of myocardial infarction, unstable angina or revascularization within the past 6 months or 2 or more risk factors for coronary artery disease including diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, and active tobacco use;
- •History of cardiac arrhythmia or arrhythmia detected by EKG during the screening visit;
- •History of syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia
- •Concurrent administration of β-blocker therapy;
- •History of a cerebrovascular accident;
- •Seizure disorder (other than with suspect or documented hypoglycemia);
- •Active treatment with any diabetes medications except for acarbose;
- •Active malignancy, except basal cell or squamous cell skin cancers;
- •Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease);
- •Known insulinoma or glucagonoma;
- •Major surgical operation within 30 days prior to screening;
- •Hematocrit < 33%;
- •Bleeding disorder, treatment with warfarin, or platelet count <50,000;
- •Blood donation (1 pint of whole blood) within the past 2 months;
- •Active alcohol abuse or substance abuse;
- •Current administration of oral or parenteral corticosteroids;
- •Pregnancy and/ or Lactation: For women of childbearing potential: there is a requirement for a negative urine pregnancy test and for agreement to use contraception during the study and for at least 1 month after participating in the study. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an intrauterine device (IUD), the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence;
- •Use of an investigational drug within 30 days prior to screening;
- •Current use of anticholinergic medications;
- •Allergy to a component of the study drug.
研究组 & 干预措施
Study drug (glucagon) first, placebo second
Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session.
干预措施: glucagon (Drug)
Study drug (glucagon) first, placebo second
Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session.
干预措施: Closed loop glucagon pump (Device)
Placebo first, study drug (glucagon) second
Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session.
干预措施: Closed loop glucagon pump (Device)
结局指标
主要结局
Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <65 mg/dL
时间窗: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
A primary endpoint for this study is the prevention of meal provoked hypoglycemia, defined as sensor glucose levels below \<65 mg/dl, comparing study drug to control.
Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <65 mg/dL
时间窗: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
A primary endpoint for this study is prevention of meal provoked hypoglycemia, defined as plasma glucose levels below \<65 mg/dl, comparing study drug to control
次要结局
- Number of Participants With Hypoglycemia Rescue Administered(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Percent Time Plasma Glucose in Range After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <60 mg/dL(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Number of Participants With Rebound Hyperglycemia (Defined as Glucose Levels Above 180 mg/dl).(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge will be conducted within two weeks of the first.)
- Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <60 mg/dL(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <55 mg/dL(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Meal Provoked Nadir Sensor Glucose(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Time to Nadir Plasma Glucose After Mixed Meal (Min)(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Time to Alarm During Mixed Meal Testing (Minutes)(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Sensor Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL)(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <55 mg/dL(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Time to Delivery (Min)(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Pain Score at Time of First Dose Delivery of Study Drug, Versus Pain Score at Time of First Dose Delivery of Placebo (Comparing First Delivery Pain Scores for Visit Where Participant Received Study Drug vs. Visit Where Participant Received Placebo).(The two study visits where participants were administered either study drug or placebo took place over 2 weeks (there was a 1 to 2 week washout period between visits).)
- Percent Time Sensor Glucose in Range After Drug Delivery After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Meal Provoked Nadir Plasma Glucose(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Time to Nadir Sensor Glucose After Mixed Meal (Min)(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Capillary Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL)(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Capillary Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL)(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Sensor Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL)(Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.)
- Pain Score at Time of Second Dose Delivery of Study Drug, Versus Pain Score at Time of Second Dose Delivery of Placebo (Comparing Second Delivery Pain Scores for Visit Where Participant Received Study Drug vs. Visit Where Participant Received Placebo).(The two study visits where participants were administered either study drug or placebo took place over 2 weeks (there was a 1 to 2 week washout period between visits).)