Glucagon Dose-Response in Patients With Post-Bariatric Hypoglycemia
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Incremental change in plasma glucose levels after administration of exogenous glucagon for each dose.
研究概览
简要总结
The purpose of the study is to determine how blood sugar levels in individuals with and without hypoglycemia after bariatric surgery respond to different doses of glucagon, a hormone that is usually present in your body that regulates blood sugar levels. In this study, there will be 4 visits to the clinical research center. In the first visit, medical history and physical exam will be performed, and blood samples will be taken to assess overall health. During visit 2, a continuous glucose monitor will be placed under the skin. (This may be combined with visit 1, depending on the schedule of visits.) In visit 3, we will test the effect of a total of 4 different doses of glucagon, in increasing doses. In visit 4, we will test the effect of a total of 3 doses of glucagon, in decreasing doses. For both visit 3 and 4, we will infuse labeled stable glucose to allow us to measure how much glucose the body is making, and will measure levels of hormones which regulate glucose, such as insulin and glucagon.
详细描述
Visit 1 (Screening) This visit will last about 2 hours.
You will be instructed to come to Joslin Diabetes Center after fasting for at least 8 hours (nothing but water for eight hours before your visit).
During the screening visit, a study team member will go over the informed consent form with you and they will help explain why this study is being done and the study procedures involved. You will have to sign the consent form before any study related procedures take place. After you sign the consent, the following tests and procedures will be done to ensure you are eligible and it is safe for you to continue study participation. These include the following:
- Review medical history and medications. There are certain medications that you may not be able to take during the study. Any changes to your medications will be reviewed with the study doctor and information will be provided to you in writing.
- Physical examination and vital signs (blood pressure, heart rate, temperature, height and weight).
- Blood tests (about one tablespoon of blood) to check your blood counts, liver and kidney tests and blood sugar
- Urine test to check for pregnancy (if you are a female of child bearing potential) that must be negative in order to continue participation.
- Surveys regarding frequency and symptoms of your low blood sugar levels (hypoglycemia)
- If you experience low blood sugars (hypoglycemia), we will ask you to complete a log including information about: prior meal, exercise (if any), what symptoms you experienced, how you treated it, and blood sugar at that moment if you checked it.
- An Electrocardiogram (ECG or EKG) will be performed.
- You will have some sticky patches applied to your chest and sometimes your arms and legs to help record electrical activity of you heart.
- Each sticky patch has a wire that is attached to a monitor.
- The ECG will only take a few minutes to complete; you need to lie still on your back until the ECG is completed.
Any changes to your medications will be reviewed with the study doctor and will be provided to you in writing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-70 years of age, inclusive, at screening.
- •Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits.
- •Males or females diagnosed with ongoing PBH, at least 2 years following Roux-en-Y gastric bypass (RYGB), with documented episodes of hypoglycemia, and history of fulfillment of Whipple's triad.
排除标准
- •Documented hypoglycemia occurring only in the fasting state (>12 hours fast);
- •Current diabetes, defined as hemoglobin A1c >6.5% or use of diabetes medications, except for acarbose or miglitol;
- •Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
- •Hepatic disease, including serum ALT or AST greater than 2 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, NYHA class II, III or IV;
- •History of myocardial infarction, unstable angina or revascularization within the past 6 months.
- •Two or more risk factors for coronary artery disease including diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, and active tobacco use.
- •History of recurrent syncope (unrelated to hypoglycemia) or active diagnosis of a cardiac arrhythmia;
- •Current administration of β-blocker therapy;
- •History of a cerebrovascular accident;
- •Seizure disorder (other than with suspect or documented hypoglycemia);
- •Active treatment with long-acting (LAR) octreotide or pasireotide;
- •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;
- •Major surgical operation within 30 days prior to screening;
- •Clinically significant anemia as defined as a 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 before any procedures.
- •Not enrolled in another study that uses an investigational drug for this condition.
- •Exclusion Criteria:
研究组 & 干预措施
ascending doses of glucagon
Participants will receive sequential ascending doses of glucagon, 75, 150, 300, 450 micrograms during the course of the study visit.
干预措施: Glucagon for Injection (Fresenius Kabi USA) (Drug)
descending doses of glucagon
Participants will receive sequential descending doses of glucagon - 300, 150, 75 micrograms
干预措施: Glucagon for Injection (Fresenius Kabi USA) (Drug)
结局指标
主要结局
Incremental change in plasma glucose levels after administration of exogenous glucagon for each dose.
时间窗: Measurement of glucose levels will occur at baseline, and then every 5 minutes, for 60 minutes.
Glycemic response to exogenous glucagon for doses, as measured by incremental change in plasma glucose levels at each 30 minute step of the dose escalation protocol. AUC will be compared in each of the 2 study visits (escalation vs. deescalation).
Endogenous glucose production (EGP) after administration of exogenous glucagon.
时间窗: Measurement of glucose levels will occur at visit 2, at baseline, and then every 5 minutes after the first dose of glucagon, for 120 minutes
Response to exogenous glucagon as measured by the incremental change in EGP from baseline during dose escalation or deescalation protocol.
次要结局
- Incremental change in plasma insulin levels during glucagon dose escalation protocol(Measurement of insulin levels will occur at baseline, and then every 30 minutes after each dosetes.)
- Insulin secretion rate in response to exogenous glucagon(Measurement of insulin secretion rates will occur at visit 2, at baseline, and then 30 minutes after each dose of glucagon)
- Incremental change in GLP1 levels during glucagon dosing protocol(Measurement will occur at visit 2, at baseline, and then every 30 minutes after each dose of glucagon)