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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

Tracking Information
First Submitted Date  ICMJE June 24, 2020
First Posted Date  ICMJE June 29, 2020
Last Update Posted Date June 29, 2020
Estimated Study Start Date  ICMJE June 23, 2020
Estimated Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2020)
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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2020)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low-dose Dasiglucagon for Prevention of Insulin-Induced Hypoglycemia in People With Type 1 Diabetes
Official Title  ICMJE Low-dose Dasiglucagon for Prevention of Insulin-Induced Hypoglycemia in People With Type 1 Diabetes
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Type 1 Diabetes
  • Hypoglycemia
Intervention  ICMJE
  • Drug: Dasiglucagon
    Abdominal s.c. administration
  • Other: Carbohydrate (dextrose tablets)
    Oral administration
Study Arms  ICMJE
  • Experimental: 80 µg s.c. dasiglucagon
    80 µg of dasiglucagon will be administered subcutaneously when plasma glucose levels reach 4.5 mmol/l
    Intervention: Drug: Dasiglucagon
  • Experimental: 120 µg s.c. dasiglucagon
    120 µg of dasiglucagon will be administered subcutaneously when plasma glucose levels reach 4.5 mmol/l
    Intervention: Drug: Dasiglucagon
  • 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
    Intervention: Other: Carbohydrate (dextrose tablets)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 26, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 1, 2021
Estimated Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christian Laugesen, MD +45 51642387 christian.laugesen@regionh.dk
Contact: Ajenthen Ranjan, MD, PhD +45 26196604 ajenthen.ranjan@regionh.dk
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04449692
Other Study ID Numbers  ICMJE H-20013256
2020-000551-12 ( EudraCT Number )
H-20013256 ( Registry Identifier: Regional Scientific Ethics Committee )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Steno Diabetes Center Copenhagen
Study Sponsor  ICMJE Steno Diabetes Center Copenhagen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christian Laugesen, MD MD, PhD Candidate
PRS Account Steno Diabetes Center Copenhagen
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP