Clinical trial NCT04163874: Alleviating Carbohydrate Counting for Patients With Type 1 Diabetes Using a Novel Insulin-plus-pramlintide Artificial Pancreas
Official title: Alleviating Carbohydrate Counting for Patients With Type 1 Diabetes Using a Novel Insulin-plus-pramlintide Artificial Pancreas: a Randomized Controlled Crossover Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Type 1 Diabetes Mellitus
Hyperglycemia, Postprandial
Keywords: type 1 diabetes
artificial pancreas
pramlintide
fiasp
hyperglycemia
closed-loop
Lead sponsor: McGill University
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2019-11-15
Enrollment: 36
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a three-way, randomized, blinded, crossover trial to compare the following strategies:

(i) Fiasp-plus-Pramlintide closed-loop delivery with a simple meal announcement (pressing a button, no carbohydrate counting) (ii) Fiasp-plus-placebo closed-loop delivery with conventional carbohydrate counting (iii) Fiasp-plus-placebo closed-loop delivery with a simple meal announcement
Primary purpose: TREATMENT

Brief summary: One of the main challenges in maintaining tight glucose control in a closed-loop system occurs at meal times. Amylin is a gluco-regulatory beta-cell hormone that is co-secreted with insulin in response to nutrient stimuli, and is deficient in patients with type 1 diabetes. Amylin, in the postprandial period, contributes to regulating glucose levels by delaying gastric emptying, suppressing nutrient-stimulated glucagon secretion, and increasing satiety. Pramlintide is a synthetic analog of the hormone amylin. A closed-loop system that delivers both insulin and pramlintide, based on glucose sensor readings, has the potential to better normalize glucose levels, especially during the post-prandial period.

The aim of this project is to assess whether co-administration of pramlintide with the improved insulin aspart formulation - Fiasp, in an artificial pancreas system, will alleviate the need for carb counting by replacing it with a simple meal announcement, without degrading the quality of glycemic control in a closed-loop therapy.


Eligibility criteria: Inclusion Criteria:

1. Signed and dated written informed consent
2. Males and females ≥ 12 years of age
3. HbA1c ≤ 12%
4. Insulin pump use for at least 3 months
5. Clinical diagnosis with type 1 diabetes for at least 12 months. The diagnosis of T1D is based on the investigator's clinical judgment; C peptide level and antibody determinations are not planned.
6. Women of child-bearing potential must be ready and able to use a highly effective method of birth control. Women of childbearing potential are females who have experienced \[the first occurrence of menstruation\] and do not meet the criteria for women not of childbearing potential. Women not of childbearing potential are females who are permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.

Exclusion Criteria:

Participants who meet any of the following criteria are not eligible for the study:

1. Current or ≤ 1 month use of other antihyperglycemic agents (SGLT2 inhibitors, GLP-1 agonists, Metformin, Acarbose, etc....).
2. Current use of glucocorticoid medication.
3. Use of medication that alters gastrointestinal motility.
4. Planned or ongoing pregnancy.
5. Breastfeeding individuals.
6. Severe hypoglycemic episode within one month of admission.
7. Severe diabetes ketoacidosis episode within one month of admission.
8. Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
9. Recent (\< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
10. Known hypersensitivity to any of the study drugs or their excipients.
11. Individuals with confirmed gastroparesis.
12. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
13. Unable to travel to research center within 3h if needed during study interventions
14. Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc.).

Study Discontinuation/Withdrawal

1. Failure to comply with the protocol.
2. Pregnancy.
3. After an event which the PI believes it is not in the best interest for the patient to continue the trial.

Primary outcomes:
measure: Each participant's time in target range
timeFrame: 12 days
measure: Mean score of the Emotional Burden section of the Diabetes Distress Scale
timeFrame: 12 days
Secondary outcomes:
measure: Each participant's percentage of time of glucose levels spent between 3.9 and 7.8 mmol/L
timeFrame: 12 days
measure: Each participant's percentage of time of glucose levels spent between 3.9 and 10 mmol/L
timeFrame: 12 days
measure: Each participant's percentage of time of glucose levels spent below 3.9, 3.3, and 2.8 mmol/L
timeFrame: 12 days
measure: Each participant's percentage of time of glucose levels spent above 7.8, 10, 13.9 and 16.7 mmol/L
timeFrame: 12 days
measure: Each participant's mean glucose level
timeFrame: 12 days
measure: Each participant's standard deviation of glucose levels as a measure of glucose variability
timeFrame: 12 days
measure: Each participant's number of hypoglycemia events defined as at least 15 min below 3.0 mmol/L
timeFrame: 12 days
measure: Each participant's number of Gastrointestinal symptoms
timeFrame: 12 days
measure: Each participant's total insulin delivery
timeFrame: 12 days
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: 3555 University Street
state: Quebec
Study officials:
References: