DiaCon Dual-Hormone Closed-Loop Glucose Control

Study Overview
=================
Brief Summary
-----------------
The ultimate T1D treatment tool is a closed-loop glucose control system, i.e. a fully automated system for intensive insulin treatment. Such system will ease the burden of constant treatment decision-making and at the same time it has the potential to safely intensify insulin therapy such that more patients can reach treatment goals. Currently, no off-the-shelf closed-loop system exists but research efforts in this field have been intensified and resulted in great progress in recent years. Most closed-loop systems consist of an insulin pump, a CGM, and a control algorithm residing on a mobile computer that continuously (every 5-15 min) computes the optimal insulin dosage from the CGM values. For daytime blood glucose control, however, we believe that the system needs to be further advanced. Consequently, we have extended our single-hormone closed-loop system such that it now includes a second pump for glucagon delivery and correspondingly we have further developed our control algorithm to compute both insulin and glucagon dosages. We hypothesize that we have developed a safe and effective dual-hormone closed-loop system for patients with type 1 diabetes and that this system is superior to single-hormone closed-loop therapy. The aims of this two-phase project are to 1) demonstrate proof-of-concept and 2) to compare dual-hormone with single-hormone closed-loop glucose control.

Official Title
-----------------
Dual-Hormone Closed-Loop Glucose Control in Type 1 Diabetes

Conditions
-----------------
Type 1 Diabetes

Intervention / Treatment
-----------------
* Device: DiaCon dual-hormone closed-loop glucose control algorithm
* Device: DiaCon single-hormone closed-loop glucose control algorithm


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: T1D ≥ 2 years Insulin pump therapy with rapid-acting analog insulin ≥ 1 year HbA1c ≤ 8.5% (69 mmol/mol) Ability and willingness to comply with all protocol procedures Exclusion Criteria: Pregnancy or nursing Plan to become pregnant or sexually active and not using adequate contraceptive methods (sterilization, intrauterine device, contraceptive pill, patch or injection) Hypoglycemia unawareness (self-reported lack of hypoglycemia symptoms when blood glucose is < 3.0 mmol/l) Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during or within 30 days prior to study participation History of coronary artery disease or congestive heart failure Abnormal ECG suggestive of coronary artery disease and increased risk of malignant arrhythmia Allergy to glucagon or lactose Pheochromocytoma Other concomitant medical or psychological condition that according to the investigator's assessment makes the patient unsuitable for study participation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Single-hormone closed-loop control<br>Closed-loop glucose control by use of insulin only by use of DiaCon single-hormone closed-loop glucose control algorithm | Device: DiaCon single-hormone closed-loop glucose control algorithm<br>* Single-hormone closed-loop glucose control<br>|
| Experimental: Dual-hormone closed-loop control<br>Closed-loop glucose control by use of insulin and glucagon by use of DiaCon dual-hormone closed-loop glucose control algorithm | Device: DiaCon dual-hormone closed-loop glucose control algorithm<br>* Dual-hormone closed-loop glucose control<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time with glucose values < 3.9 mmol/l as measured by Continuous Glucose Monitoring and Yellow Spring Instruments |  | Every 5 minutes for 33 hours (total duration of each study arm) | 
| Number of CHO interventions to treat hypoglycemia |  | 33 hours (total duration of each study arm) |