A Randomized, Three-way, Crossover Study to Assess the Efficacy of Fast-acting Insulin-plus-pramlintide Closed-loop Co-administration, Regular Insulin-plus-pramlintide Closed-loop Co-administration, and Fast-acting Insulin-alone Closed-loop Infusion in Regulating Glucose Levels Over a 24-hour Period in Adults With Type 1 Diabetes in Inpatient Settings.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Percentage of time of plasma glucose levels spent in target range. Target range is defined to be between 3.9 and 10.0 mmol/L of regular insulin-plus-pramlintide closed-loop delivery vs. fast-acting insulin-alone closed-loop delivery.
研究概览
简要总结
The closed-loop delivery system is composed of an insulin pump, a continuous glucose sensor and a dosing algorithm that calculates the insulin dose to infuse based on sensor readings. Pramlintide is a drug and an analog of amylin, a hormone that is co-secreted with insulin in healthy individuals, and is deficient in people with type 1 diabetes. Co-injection of pramlintide with insulin at meal times improves glucose control in type 1 diabetes. Literature data suggests that regular insulin may better match the effect of pramlintide compared to rapid insulin in regulating post-prandial glucose levels.
The purpose of this study is to compare the effectiveness of 3 strategies to control your day-and-night glucose levels:
- rapid insulin-alone closed-loop delivery;
- rapid insulin-plus-pramlintide closed-loop delivery;
- regular insulin-plus-pramlintide closed-loop delivery.
The primary hypotheses are:
- During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and fast-acting insulin improves glucose control compared to fast-acting insulin-alone infusion.
- During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and regular insulin improves glucose control compared to fast-acting insulin-alone infusion.
详细描述
The closed-loop delivery system is composed of an insulin pump, a continuous glucose sensor and a dosing algorithm that calculates the insulin dose to infuse based on sensor readings. Pramlintide is a drug and an analog of amylin, a hormone that is co-secreted with insulin in healthy individuals, and is deficient in people with type 1 diabetes. Co-injection of pramlintide with insulin at meal times improves glucose control in type 1 diabetes.
Literature data suggests that the pharmacodynamics of regular insulin may better match the effect of pramlintide compared to the pharmacodynamics of fast-acting insulin. Moreover, the cost of regular insulin is significantly lower than fast-acting insulin. Therefore, if a similar (or better) glucose profile can be achieved with regular insulin-plus-pramlintide compared to fast-acting insulin-plus-pramlintide, then a co-formulation employing regular insulin should be prioritized.
Therefore, in this protocol, we aim to assess the effect of the simultaneous, closed-loop, basal-bolus infusion of pramlintide with insulin at a fixed ratio in controlling glucose levels. In the first experimental arm, we propose to infuse pramlintide with fast-acting insulin. In the second experimental arm, pramlintide will be infused with regular insulin. The control arm will be fast-acting insulin-alone closed-loop system.
The aim of the study is to assess the efficacy of the simultaneous, closed-loop, basal-bolus infusion of pramlintide with fast-acting insulin at a fixed ratio and pramlintide with regular insulin at a fixed ratio in controlling glucose levels compared to fast-acting insulin-alone closed-loop infusion.
The investigators aim to conduct a randomized, three-way, crossover trial to compare the efficacy of 1) fast-acting insulin-plus-pramlintide closed-loop delivery, 2) regular insulin-plus-pramlintide closed-loop delivery, and 3) fast-acting insulin-alone closed-loop delivery in regulating glucose levels over a period of 24 hours in a study on adults in inpatient settings. Insulin (fast-acting and regular) and pramlintide are given with fixed ratio (6 µg of pramlintide for each unit of insulin).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females ≥ 18 years of age.
- •Clinical diagnosis of type 1 diabetes for at least 12 months. (The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.)
- •The subject will have been on insulin pump therapy for at least 6 months.
- •HbA1c ≤ 10%.
排除标准
- •Current or ≤ 1 month use of other antihyperglycemic agents (SGLT2, GLP-1, Metformin, Acarbose, etc....).
- •Severe hypoglycemic episode within one month of screening.
- •Severe diabetes keto-acidosis episode within one month of screening.
- •Planned or ongoing pregnancy.
- •Known or suspected allergy to the study drugs.
- •Gastroparesis.
- •Use of prokinetic drugs that stimulate gastric emptying (domperidone, cisapride, metoclopramide).
- •Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
- •Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
- •Current use of glucocorticoid medication.
- •Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
- •Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc.).
研究组 & 干预措施
Rapid Insulin-alone closed-loop delivery
Rapid Insulin will be delivered by subcutaneous infusion. Interventions: 24-hour inpatient intervention Drug: Rapid acting Insulin (aspart, lispro, glulisine)
干预措施: 24-hour inpatient intervention (Other)
Rapid Insulin-plus-pramlintide closed-loop delivery
Rapid insulin and pramlintide will be delivered by subcutaneous infusion using a fixed ratio (6 µg pramlintide/unit insulin).
Interventions: 24-hour inpatient intervention Drug: Rapid acting Insulin (aspart, lispro, glulisine) Drug: Pramlintide
干预措施: 24-hour inpatient intervention (Other)
Regular Insulin-plus-pramlintide closed-loop delivery
Regular insulin and pramlintide will be delivered by subcutaneous infusion using a fixed ratio (6 µg pramlintide/unit insulin).
Interventions: 24-hour inpatient intervention Drug: Regular Insulin (humulin R) Drug: Pramlintide
干预措施: 24-hour inpatient intervention (Other)
结局指标
主要结局
Percentage of time of plasma glucose levels spent in target range. Target range is defined to be between 3.9 and 10.0 mmol/L of regular insulin-plus-pramlintide closed-loop delivery vs. fast-acting insulin-alone closed-loop delivery.
时间窗: Up to 24 hours
Percentage of time of plasma glucose levels spent in target range. Target range is defined to be between 3.9 and 10.0 mmol/L of fast-acting insulin-plus-pramlintide closed-loop delivery vs. fast-acting insulin-alone closed-loop delivery.
时间窗: Up to 24 hours
次要结局
- Total pramlintide delivery.(Up to 24 hours)
- Standard deviation of glucose levels as a measure of glucose variability.(Up to 24 hours)
- Mean plasma amylin concentration.(Up to 24 hours)
- Total insulin delivery.(Up to 24 hours)
- Mean plasma glucose level during: a. the overall study period; b. overnight period.(Up to 24 hours)
- Percentage of time (8:00-8:00) of plasma glucose levels spent: a. 3.9-7.8 mmol/L; b. 3.9-10 mmol/L; c. <3.9 mmol/L; d. <3.3 mmol/L; e. <2.8 mmol/L; f. >7.8 mmol/L; g. >10 mmol/L; h. >13.9 mmol/L; i. >16.7 mmol/L(Up to 24 hours)
- Mean plasma glucagon concentration.(Up to 24 hours)
- Number of subjects experiencing hypoglycemia requiring oral treatment during: a. the overall study period; b. the night.(Up to 24 hours)
- Percentage of time of plasma glucose levels spent in target range, comparing fast-acting insulin-plus-pramlintide closed-loop delivery vs. regular insulin-plus-pramlintide closed-loop delivery.(Up to 24 hours)
- Percentage of overnight time (23:00-8:00) of plasma glucose levels: a. 3.9-7.8 mmol/L; b. 3.9-10 mmol/L; c. <3.9 mmol/L; d. <3.3 mmol/L; e. <2.8 mmol/L; f. >7.8 mmol/L; g. >10 mmol/L; h. >13.9 mmol/L; i. >16.7 mmol/L(Up to 24 hours)
- Mean plasma insulin concentration.(Up to 24 hours)
- Gastrointestinal symptoms during the treatment optimization (i.e., the minimum 10 days prior to the 24-hour closed-loop visits) and during the 24-hour closed-loop visits.(Up to 24 hours)
研究者
Ahmad Haidar
Assistant Professor
McGill University