Effect of Basal-Bolus Closed-Loop Co-Administration of Insulin and Pramlintide on Improving the Glycemic Control in Type 1 Diabetes

NCT02814123 | Completed Phase 2

• 1 other identifier: MAP-1
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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:

1. 1.rapid insulin-alone closed-loop delivery;
2. 2.rapid insulin-plus-pramlintide closed-loop delivery;
3. 3.regular insulin-plus-pramlintide closed-loop delivery.
4. 4.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.
5. 5.During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and regular insulin improves glucose control compared to fast-acting insulin-alone infusion.

Conditions

Diabetes Mellitus, Type 1

Keywords

Diabetes Mellitus, Type 1; Pramlintide; Artificial Pancreas; Closed-Loop System; Insulin

Outcome Measures

Primary Outcomes (2)

• 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.

  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 regular insulin-plus-pramlintide closed-loop delivery vs. fast-acting insulin-alone closed-loop delivery.

  Up to 24 hours

Secondary Outcomes (12)

• 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 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

• 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

• Standard deviation of glucose levels as a measure of glucose variability.

  Up to 24 hours

• Total insulin delivery.

  Up to 24 hours

Study Arms (3)

Rapid Insulin-alone closed-loop delivery

ACTIVE COMPARATOR

Rapid Insulin will be delivered by subcutaneous infusion. Interventions: 24-hour inpatient intervention Drug: Rapid acting Insulin (aspart, lispro, glulisine)

Other: 24-hour inpatient intervention

Rapid Insulin-plus-pramlintide closed-loop delivery

EXPERIMENTAL

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

Other: 24-hour inpatient intervention

Regular Insulin-plus-pramlintide closed-loop delivery

EXPERIMENTAL

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

Other: 24-hour inpatient intervention

Interventions

24-hour inpatient intervention OTHER

Subjects will be admitted at the research facility at 7:30. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. Each 24-hour intervention visit includes 3 standardized meals (8:00, 12:00, and 17:00), an evening snack (21:00) and an overnight stay. The glucose level as measured by the real time sensor will be entered manually into the computer every 10 minutes. The insulin and pramlintide pumps' infusion rates will then be changed manually based on the computer generated recommendation, while still maintaining the ratio. The computer generated recommendations are based on a predictive algorithm.

Rapid Insulin-alone closed-loop delivery; Rapid Insulin-plus-pramlintide closed-loop delivery; Regular Insulin-plus-pramlintide closed-loop delivery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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.).

Sponsors & Collaborators

• McGill University: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

McGill University Health Centre

Montreal, Quebec, Canada

Location

Related Publications (2)

• Haidar A, Tsoukas MA, Bernier-Twardy S, Yale JF, Rutkowski J, Bossy A, Pytka E, El Fathi A, Strauss N, Legault L. A Novel Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Randomized Controlled Crossover Trial. Diabetes Care. 2020 Mar;43(3):597-606. doi: 10.2337/dc19-1922. Epub 2020 Jan 23.

  PMID: 31974099 DERIVED

• Tsoukas M, Rutkowski J, El-Fathi A, Yale JF, Bernier-Twardy S, Bossy A, Pytka E, Legault L, Haidar A. Accuracy of FreeStyle Libre in Adults with Type 1 Diabetes: The Effect of Sensor Age. Diabetes Technol Ther. 2020 Mar;22(3):203-207. doi: 10.1089/dia.2019.0262. Epub 2020 Jan 23.

  PMID: 31613140 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Study Officials

• Ahmad Haidar

  McGill University

  PRINCIPAL INVESTIGATOR

• Laurent Legault

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 22, 2016
• First Posted: June 27, 2016
• Study Start: January 13, 2017
• Primary Completion: July 8, 2018
• Study Completion: July 8, 2018
• Last Updated: February 17, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)