Co-administration of Pramlintide and Insulin Via an Automated Dual-hormone Artificial Pancreas System in Adults With Type 1 Diabetes

Type 1 Diabetes Clinical Trial

Official title:

Co-administration of Pramlintide and Insulin Via an Automated Dual-hormone Artificial Pancreas System to Regulate Glucose Levels in Adults Living With Type 1 Diabetes: a Randomized, Controlled, Crossover Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04243629
• Other study ID #: 2020-6258
• Status: Recruiting
• Phase: N/A
• Start date: November 12, 2021
• Est. completion date: April 2024

Study information

• Verified date: March 2023
• Source: McGill University
• Contact: Elisa Cohen, BSs
• Phone: 6472372366
• Email: elisa.cohen[@]mail.mcgill.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 rapid insulin in an artificial pancreas system will improve glycemic control in adults with Type 1 Diabetes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 26
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed and dated written informed consent

2. Males and females = 18 years of age

3. HbA1c = 11% (this is so we also include patient that are potentially missing some meal boluses)

4. Insulin pump use for at least 6 months and actively performing carbohydrate counting

5. Clinical diagnosis of 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:

1. Current total daily dose < 0.4 units/kg (we wish to exclude participants who would still be considered in honeymoon period).

2. Current or = 1 month use of other antihyperglycemic agents (SGLT2 inhibitors, GLP-1 agonists, Metformin, Acarbose, etc.…).

3. Current use of glucocorticoid medication (except low stable dose and inhaled steroids).

4. Anticipated need to use acetaminophen during study participation

5. Use of medication that alters gastrointestinal motility.

6. Planned or ongoing pregnancy.

7. Breastfeeding individuals.

8. Severe hypoglycemic episode within 3 months of admission.

9. Severe diabetes ketoacidosis episode within 3 months of admission.

10. Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.

11. Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.

12. Known hypersensitivity to any of the study drugs or their excipients.

13. Individuals with confirmed gastroparesis.

14. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.

15. In the opinion of the investigator, a participant who is unable or unwilling to observe the contraindications of the study devices.

16. Unable to travel to research center within 3h if needed during study interventions

17. Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc.).

Discontinuation Criteria:

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.

4. The subject wants to withdraw consent to participate

5. The subject needs to take any medications that are contraindicated in the study

6. The subject can no longer be treated with the study medication for other reasons

7. The subject experiences severe hypoglycaemia requiring hospitalization or repeated hypoglycaemia requiring assistance to treat.

8. The subject fails to follow instructions given about the trial

9. The Study Team has decided to discontinue or terminate the clinical trial prematurely

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hyperglycemia
• Postprandial Hyperglycemia
• Type 1 Diabetes

Intervention

Drug:
• Rapid-Acting Insulin
Novorapid or Humalog insulin delivered in a basal-bolus manner.
• Placebo
Placebo (saline) delivered in a basal-bolus manner at a fixed ratio with insulin.
• Pramlintide Acetate
Pramlintide acetate delivered in a basal-bolus manner at a fixed ratio with insulin.

Device:
• Artificial Pancreas
Tandem insulin pump, Dexcom G6 sensor, study smartphone running the iMAP algorithm.

Locations

Country	Name	City	State
Canada	McGill University Health Centre	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
McGill University	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time in target range	Time each participant spent with glucose level in target range (3.9 - 10.0 mmol/L)	4 weeks
Secondary	Time between 3.9 - 7.8 mmol/L	Percentage of time each participant spent with glucose levels between 3.9 - 7.8 mmol/L	4 weeks
Secondary	Time below 3,9, 3.3, and 2.8 mmol/L	Percentage of time each participant spent with glucose levels below 3.9, 3.3, and 2.8 mmol/L	4 weeks
Secondary	Time above 7.8, 10.0, 13.9, 16.7 mmol/L	Percentage of time each participant spent with glucose levels above 7.8, 10.0, 13.9, and 16.7 mmol/L	4 weeks
Secondary	Mean glucose level	Each participant's mean glucose level	4 weeks
Secondary	Total insulin delivery	Each participant's total insulin delivery	4 weeks
Secondary	Standard deviation and coefficient of variance	Each participant's standard deviation and coefficient of variance of glucose levels as a measure of glucose variability	4 weeks
Secondary	Gastrointestinal symptoms	Number of each participant's gastrointestinal symptoms	4 weeks
Secondary	Number of hypoglycemia events	Each participant's number of hypoglycemia events defined as at least 15 min below 3.0 mmol/L with the end of the event being 15 minutes > 3.9 mmol/L.	4 weeks