Low-dose Dasiglucagon for Prevention of Insulin-Induced Hypoglycemia in People With Type 1 Diabetes

NCT ID: NCT04449692

Last Updated: 2021-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-02
• Study Completion Date: 2021-01-04

Brief Summary

The aim of the study is to compare the efficacy of low-dose dasiglucagon (Zealand Pharma, Denmark) to oral carbohydrate consumption for prevention of s.c. insulin-induced hypoglycemia in CSII- and MDI-treated people with type 1 diabetes.

Detailed Description

Near-normalization of blood glucose levels through intensive insulin therapy has shown to reduce the risk of diabetes late complications, but the approach is associated with two major side effects: hypoglycemia and weight gain. Although management of hypoglycemia through oral carbohydrate consumption is generally effective, the approach can lead to excessive carbohydrate intake and cause rebound hyperglycemia. It has previously been demonstrated that subcutaneous (s.c.) low-dose glucagon can be utilized to effectively treat mild hypoglycemia in people with type 1 diabetes. However, the instability in aqueous solution of currently available glucagon and the need for reconstitution with sterile water immediately prior to administration has limited its clinical role outside emergency settings. Due to the stability and ready-to-use formulation, dasiglucagon does not hold the limitations known for the currently available glucagon preparations.

The aim of this randomized, partially single-blinded, three-arm cross-over study is to compare the efficacy of low-dose dasiglucagon (80 and 120 μg) to oral carbohydrate (15 g) consumption for prevention of s.c. insulin-induced hypoglycemia in CSII- and MDI-treated people with type 1 diabetes. On each study visit (separated by ≥ 3 days), an initial insulin bolus will be administered (at t = 0) aiming for a plasma glucose (PG) level of 3.0 mmol/l. When reaching 4.5 mmol/l, the intervention (s.c. dasiglucagon or oral carbohydrates) will be administered (t-intervention = 0), whereafter PG will me monitored for an additional 180 min.

Conditions

Type 1 Diabetes; Hypoglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

80 µg s.c. dasiglucagon

80 µg of dasiglucagon will be administered subcutaneously when plasma glucose levels reach 4.5 mmol/l

Group Type: EXPERIMENTAL

Dasiglucagon

Intervention Type: DRUG

Abdominal s.c. administration

120 µg s.c. dasiglucagon

120 µg of dasiglucagon will be administered subcutaneously when plasma glucose levels reach 4.5 mmol/l

Group Type: EXPERIMENTAL

Dasiglucagon

Intervention Type: DRUG

Abdominal s.c. administration

15 g oral carbohydrate (dextrose tablets)

15 g of oral carbohydrate (dextrose tablets) will be administered when plasma glucose levels reach 4.5 mmol/l

Group Type: ACTIVE_COMPARATOR

Carbohydrate (dextrose tablets)

Intervention Type: OTHER

Oral administration

Interventions

Dasiglucagon

Abdominal s.c. administration

Intervention Type: DRUG

Carbohydrate (dextrose tablets)

Oral administration

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age 18-64 years
• Duration of T1D ≥ 3 years
• Use of CSII or MDI therapy for ≥ 6 months
• Current use of Novorapid (change from another fast-acting insulin to Novorapid prior to study initiation is allowed)
• HbA1c ≤ 8.0%
• Regular use of carbohydrate counting in the judgement of the investigator

Exclusion Criteria

• Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to study start
• History of allergy or intolerance to glucagon or glucagon-like products
• Patients with pheochromocytoma
• Clinically significant ECG abnormalities
• Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (sterilization, intrauterine device, contraceptive pill, patch or injection)
• Inability to understand the individual information and to give informed consent
• Current participation in another clinical trial that, in the judgment of the principle investigator, will compromise the results of the study or the safety of the subject
• Other concomitant medical or psychological condition that, according to the investigator's assessment, makes the individual unsuitable for study participation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Laugesen, MD

Role: PRINCIPAL_INVESTIGATOR

MD, PhD Candidate

Locations

Steno Diabetes Center Copenhagen

Gentofte Municipality, , Denmark

Countries

Denmark

References

Laugesen C, Ranjan AG, Schmidt S, Norgaard K. Low-Dose Dasiglucagon Versus Oral Glucose for Prevention of Insulin-Induced Hypoglycemia in People With Type 1 Diabetes: A Phase 2, Randomized, Three-Arm Crossover Study. Diabetes Care. 2022 Jun 2;45(6):1391-1399. doi: 10.2337/dc21-2304.

Reference Type: DERIVED

PMID: 35475907 (View on PubMed)

Other Identifiers

2020-000551-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

H-20013256

Identifier Type: REGISTRY

Identifier Source: secondary_id

H-20013256

Identifier Type: -

Identifier Source: org_study_id