Effect of Basal-Bolus Closed-Loop Co-Administration of Insulin and Pramlintide on Improving the Glycemic Control in Type 1 Diabetes
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About
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.
Full description
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).
Before each 24-hour intervention visit, the participant's insulin therapy (basal rates and insulin-to-carbohydrate ratios) will be optimized for a minimum of 10 days, with a target of 14 days.
There will be a wash-out period of 0 to 42 days between the three intervention arms (termination of 24-hr intervention and start of next optimization period).
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.
Enrollment
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Volunteers
Inclusion criteria
- 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%.
Exclusion criteria
- 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.).
Trial design
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Interventional model
Masking
28 participants in 3 patient groups
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Data sourced from clinicaltrials.gov
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