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

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ClinicalTrials.gov Identifier: NCT04449692
Recruitment Status : Recruiting
First Posted : June 29, 2020
Last Update Posted : June 29, 2020
Sponsor:
Information provided by (Responsible Party):
Steno Diabetes Center Copenhagen

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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Hypoglycemia Drug: Dasiglucagon Other: Carbohydrate (dextrose tablets) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Single-blinded, randomized (using blocks of 3/6 and stratification by treatment modality), three-arm crossover study
Masking: Single (Participant)
Masking Description: Partially single-blinded (oral carbohydrate administration will not be blinded)
Primary Purpose: Treatment
Official Title: Low-dose Dasiglucagon for Prevention of Insulin-Induced Hypoglycemia in People With Type 1 Diabetes
Estimated Study Start Date : June 23, 2020
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : February 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 80 µg s.c. dasiglucagon
80 µg of dasiglucagon will be administered subcutaneously when plasma glucose levels reach 4.5 mmol/l
Drug: Dasiglucagon
Abdominal s.c. administration

Experimental: 120 µg s.c. dasiglucagon
120 µg of dasiglucagon will be administered subcutaneously when plasma glucose levels reach 4.5 mmol/l
Drug: Dasiglucagon
Abdominal s.c. administration

Active Comparator: 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
Other: Carbohydrate (dextrose tablets)
Oral administration




Primary Outcome Measures :
  1. Difference between study visits in time (min) in hypoglycemia (plasma glucose < 3.9 mmol/l) from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]

Secondary Outcome Measures :
  1. Difference between study visits in incidence rate of hypoglycemia (plasma glucose < 3.9 mmol/l) from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  2. Difference between study visits in incidence rate of level 2 hypoglycemia (plasma glucose < 3.0 mmol/l) from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  3. Difference between study visits in incidence rate of rebound hyperglycemia (plasma glucose > 10 mmol/l) from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  4. Difference between study visits in nadir plasma glucose concentration from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  5. Difference between study visits in peak plasma glucose concentration from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  6. Difference between study visits in incremental peak in plasma glucose concentration from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  7. Difference between study visits in mean plasma glucose concentration from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  8. Difference between study visits in time (min) from intervention to first increase in plasma glucose concentration of 1.1 mmol/l [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  9. Difference between study visits in plasma glucose Area Under the Curve (AUC) from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  10. Difference between study visits in time (min) to peak plasma glucose concentration from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  11. Difference between study visits in time (min) in range (plasma glucose ≥ 3.9 mmol/l and 10.0 mmol/l) from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  12. Difference between study visits in time (min) in hyperglycemia (plasma glucose > 10 mmol/l) from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  13. Difference between study visits in time (%) in hypoglycemia (plasma glucose < 3.9 mmol/l) (per protocol) from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  14. Difference between study visits in incidence rate of rescue carbohydrate administration from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  15. Difference between study visits in time (min) to rescue carbohydrate administration from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  16. Difference between study visits in plasma dasiglucagon Area Under the Curve (AUC) from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  17. Difference between study visits in peak plasma dasiglucagon concentration from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  18. Difference between study visits in time to peak plasma dasiglucagon concentration from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  19. Difference between study visits in serum insulin concentration at visit start (t = 0) and immediately before administration of the intervention (t-intervention = 0) [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  20. Difference between study visits in serum insulin AUC from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  21. Difference between study visits in dose (units) of insulin bolus at study start (t = 0) [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  22. Difference between study visits in change in Edinburgh Hypoglycemia Symptoms Scale (EHSS) from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  23. Difference between study visits in change in visual analogue scale (VAS) for nausea, headache, stomach ache, injection site pain, palpitations and hunger from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]
  24. Difference between study visits in incidence rate of vomiting from 0-180 minutes post-intervention [ Time Frame: Study visit 1 (day 1), study visit 2 (estimated day 4) and study visit 3 (estimated day 7) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (for CSII and MDI-treated participants) and Tresiba (for MDI-treated participants).
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04449692


Contacts
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Contact: Christian Laugesen, MD +45 51642387 christian.laugesen@regionh.dk
Contact: Ajenthen Ranjan, MD, PhD +45 26196604 ajenthen.ranjan@regionh.dk

Locations
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Denmark
Steno Diabetes Center Copenhagen Recruiting
Gentofte, Denmark, 2820
Contact: Christian Laugesen, MD    +45 51642387    christian.laugesen@regionh.dk   
Contact: Ajenthen Ranjan, MD, PhD       ajenthen.ranjan@regionh.dk   
Sponsors and Collaborators
Steno Diabetes Center Copenhagen
Investigators
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Principal Investigator: Christian Laugesen, MD MD, PhD Candidate
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Responsible Party: Steno Diabetes Center Copenhagen
ClinicalTrials.gov Identifier: NCT04449692    
Other Study ID Numbers: H-20013256
2020-000551-12 ( EudraCT Number )
H-20013256 ( Registry Identifier: Regional Scientific Ethics Committee )
First Posted: June 29, 2020    Key Record Dates
Last Update Posted: June 29, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Steno Diabetes Center Copenhagen:
Type 1 Diabetes
Hypoglycemia
Dasiglucagon
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases