Dual-hormone Closed-loop Glucose Control in Type 1 Diabetes

NCT04053712 | Completed Phase 4 DMC

• 5 other identifiers: H-190263312019-001631-3120190435282019043269CIV-19-04-028465
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Despite recent pharmacological and technological advantages, hypoglycemia remains to be the key limiting factor in achieving optimal glycemic control in people with type 1 diabetes. State-of-the-art treatment for type 1 diabetes is insulin in pens or pumps that focus on reducing hyperglycemia after relative insulin deficiency e.g. after food intake. In recent years, we focused on adding low-dose glucagon to insulin therapies for the treatment and prevention of hypoglycemia - referred to as "dual-hormone treatment". We have shown that low-dose glucagon is efficient in treating mild hypoglycemia and that several factors may affect its glucose response. Our next step is to test whether the combined delivery of insulin and glucagon can improve glucose control in individuals with type 1 diabetes. In this proposal, we want to test the efficacy, safety and feasibility of a dual-hormone closed-loop system, also known as an artificial pancreas. The closed-loop system involves automatic infusion of glucagon and insulin based on continuous glucose measurements. The system will be tested in a 33-hour in-clinic study comparing the glucose control by the combined automatic delivery of insulin and glucagon with the automatic delivery of insulin-only. The study is performed at Steno Diabetes Center Copenhagen (SDCC) in collaboration with the Technical University of Denmark (DTU). We expect that the study will clarify whether low-dose glucagon added to insulin therapy can improve the glucose control in adults with type 1 diabetes. We believe that the utilization of glucagon will allow for a weight neutral optimization of glucose control, reduce risk of hypoglycemia and reduce disease burden that will reduce diabetes complications and cardiovascular diseases.

Conditions

Type 1 Diabetes; Hypoglycemia

Keywords

Closed-loop; Dual-hormone; Glucagon; FiAsp; Artificial pancreas

Outcome Measures

Primary Outcomes (2)

• Percentage of time with glucose values < 3.9 mmol/l as measured by glucose sensor

  33 hours

• Number of carbohydrate interventions to treat hypoglycemia

  Carbohydrate interventions are predefined and provided in case of hypoglycemia

  33 hours

Secondary Outcomes (32)

• Percentage of time with glucose values < 3.9 mmol/l as measured by venous plasma glucose

  33 hours

• Percentage of participants achieving (A) time in range (3.9-10 mmol/l) > 70 %, (B) time in alert hypoglycemia (<3.9 mmol/l) < 4 %, and (C) time in clinical hypoglycemia (<3.0 mmol) < 1% as measured by glucose sensor and venous plasma glucose

  33 hours

• Mean blood glucose value measured by glucose sensor and venous plasma glucose

  33 hours

• Percentage of time with glucose values in the range 3.9-8.0 mmol/l measured by glucose sensor and venous plasma glucose

  33 hours

• Percentage of time with glucose values in the range 3.9-10.0 mmol/l measured by glucose sensor and venous plasma glucose

  33 hours

Study Arms (2)

Single-hormone

PLACEBO COMPARATOR

FiAsp (R) - Saline

Device: Closed-loop system

Dual-hormone

ACTIVE COMPARATOR

FiAsp(R) - GlucaGen(R)

Drug: Glucagon; Device: Closed-loop system

Interventions

Glucagon DRUG

GlucaGen(R), Novo Nordisk, DK

Dual-hormone

Closed-loop system DEVICE

Closed-loop system comprise of two DANA RS (R) insulin pumps (FiAsp-GlucaGen vs FiAsp-saline), one DexCom G6 sensor, and a smartphone for the control algorithm.

Dual-hormone; Single-hormone

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• T1D ≥ 2 years
• Insulin pump therapy ≥ 1
• Currently treated with FiAsp® - insulin

You may not qualify if:

• Pregnancy or nursing
• Inability and willingness to comply with all protocol procedures, e.g. exercise, sleeping, blood sampling, and meal consumption
• 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
• Withdrawal criteria
• In case of pregnancy (or desire for pregnancy), female subjects are withdrawn
• Lack of compliance to any of the important study procedures in the discretion of the investigator
• Unacceptable adverse effects in the discretion of the investigator
• Withdrawal on participants request will be accepted at any time without further justification

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• Technical University of Denmark: collaborator
• University of Copenhagen: collaborator
• Danish Diabetes Academy: collaborator

Study Sites (1)

Steno Diabetes Center Copenhagen

Gentofte Municipality, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Interventions

Glucagon

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Ajenthen G Ranjan, MD, PhD

  Steno Diabetes Center Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized single-blinded placebo-controlled cross-over 33-hour in-clinic study in adults with type 1 diabetes.

Study Record Dates

• First Submitted: August 8, 2019
• First Posted: August 12, 2019
• Study Start: July 16, 2019
• Primary Completion: March 19, 2021
• Study Completion: March 19, 2021
• Last Updated: August 18, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

DK (1)