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The Effect of Rapid and Slow Glucose Fall on the Subsequent Glucose Production in People With Type 1 Diabetes (RaSlo-19)

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ClinicalTrials.gov Identifier: NCT04098549
Recruitment Status : Completed
First Posted : September 23, 2019
Last Update Posted : June 25, 2020
Sponsor:
Collaborator:
University of Copenhagen
Information provided by (Responsible Party):
Steno Diabetes Center Copenhagen

Brief Summary:
In the effort of better understanding the glucose control in people with type 1 diabetes, in-depth insight into the physiology of hepatic glucose production and its influencing factors is essential. Previously, a number of potential influencing factors of hepatic glucose production have been investigated, including insulin-on-board, low carbohydrate diet, preceding ethanol intake, exercise and multiple stimulations of hepatic glucose production. Previous post-hoc analysis of dual-hormone closed-loop systems has indicated that the rate of fall in blood glucose influences the following stimulation of hepatic glucose response. However, the rate of fall in blood glucose is highly related to insulin levels, which may explain those findings. Thus, in this study the investigators want to examine whether the different rates of fall in blood glucose with similar insulin levels on board affect the hepatic glucose response in individuals with type 1 diabetes. In the study, which will be conducted at Steno Diabetes Center Copenhagen, participants will complete two study visits. On each visit, a hypoglycemic clamp technique will be used to lower the blood glucose levels of the participants (using either a rapid or slow decline rate), whereupon hepatic glucose production will be stimulated using low-dose glucagon. The study days are divided into four phases: 1) preparation phase, 2) hyperinsulinemic euglycemic phase (stabilization of blood glucose), 3) hyperinsulinemic hypoglycemic phase (rapid or slow decline in blood glucose) and 4) post-glucagon administration phase. This design will allow the investigators to examine whether differences in hepatic glucose response exist depending on preceding rate of fall in blood glucose. We hypothesize that the rate of fall in blood glucose does not affect the hepatic glucose production.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Blood Glucose, Low Glucose Metabolism Disorders Other: Rapid lowering of plasma glucose Other: Slow lowering of plasma glucose Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: The Effect of Rapid and Slow Glucose Fall on the Subsequent Glucose Production in People With Type 1 Diabetes
Actual Study Start Date : September 12, 2019
Actual Primary Completion Date : January 15, 2020
Actual Study Completion Date : January 15, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Dextrose

Arm Intervention/treatment
Experimental: Rapid-Slow
This arm will begin with intervention "rapid" (rapid rate of fall in plasma glucose) for the first study visit and proceed to intervention "slow" (slow rate of fall in plasma glucose) for the second study visit.
Other: Rapid lowering of plasma glucose
Rapid lowering of plasma glucose using hypoglycemic clamp technique

Other: Slow lowering of plasma glucose
Slow lowering of plasma glucose using hypoglycemic clamp technique

Experimental: Slow-Rapid
This arm will begin with intervention "slow" (slow rate of fall in plasma glucose) for the first study visit and proceed to intervention "rapid" (rapid rate of fall in plasma glucose) for the second study visit.
Other: Rapid lowering of plasma glucose
Rapid lowering of plasma glucose using hypoglycemic clamp technique

Other: Slow lowering of plasma glucose
Slow lowering of plasma glucose using hypoglycemic clamp technique




Primary Outcome Measures :
  1. Positive incremental area under the glucose curve (PI-AUC) (using the plasma glucose concentration before glucagon administration as basal level) [ Time Frame: from 0-120 minutes after glucagon administration ]

Secondary Outcome Measures :
  1. Total area under the glucose curve (AUC) [ Time Frame: from 0-120 minutes after glucagon administration ]
  2. Peak plasma glucose [ Time Frame: from 0-120 minutes after glucagon administration ]
  3. Incremental plasma glucose peak [ Time Frame: from 0-120 minutes after glucagon administration ]
  4. Time-to-peak plasma glucose [ Time Frame: from 0-120 minutes after glucagon administration ]
  5. Plasma glucose level [ Time Frame: 120 minutes after glucagon administration ]
  6. Duration of plasma glucose above 4.0 mmol/l [ Time Frame: from 0-120 minutes after glucagon administration ]
  7. Duration of plasma glucose above baseline [ Time Frame: from 0-120 minutes after glucagon administration ]
  8. Number of subjects who, after reaching a plasma glucose value > 3.9 mmol/l following glucagon administration, maintain a plasma glucose level in the range of 3.9-10 mmol/l [ Time Frame: throughout phase 4 (until 120 minutes after glucagon administration) ]
  9. Number of subjects who, after reaching a PG > 3.9 mmol/l following glucagon administration, maintain a plasma glucose level in the range of 3.9-7.8 mmol/l [ Time Frame: throughout phase 4 (until 120 minutes after glucagon administration) ]
  10. Time from glucagon administration to reaching a plasma glucose level > 3,9 mmol/l [ Time Frame: from 0-120 minutes after glucagon administration ]
  11. Duration of a plasma glucose level in the range of 3.9-10 mmol/l [ Time Frame: from 0-120 minutes after glucagon administration ]
  12. Duration of a plasma glucose level in the range of 3.9-7.8 mmol/l [ Time Frame: from 0-120 minutes after glucagon administration ]
  13. Change in insulin levels (measured as area under the curve) [ Time Frame: 0-120 minutes after glucagon administration ]
  14. Change in insulin levels (measured as peak change) [ Time Frame: from baseline to 120 minutes after glucagon administration ]
  15. Change in glucagon levels (measured as area under the curve) [ Time Frame: 0-120 minutes after glucagon administration ]
  16. Change in glucagon levels (measured as peak change) [ Time Frame: 0-120 minutes after glucagon administration ]
  17. Average changes in Edinburgh Hypoglycemia Scale [ Time Frame: measured at baseline, 5 minutes prior to the end of phase 2, 5 minutes prior to the end of phase 3 and 30 and 115 minutes after glucagon administration ]
  18. Average change in visual analogue scale score for nausea, headache, stomach ache and palpitations [ Time Frame: measured at baseline, 5 minutes prior to the end of phase 2, 5 minutes prior to the end of phase 3 and 30 and 115 minutes after glucagon administration ]
  19. Number of subjects experiencing vomiting [ Time Frame: from 0-120 minutes after glucagon administration ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-70 years
  • Duration of Type 1 Diabetes ≥ 3 years
  • Insulin pump use > 6 months

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
  • Allergy or intolerance to lactose or GlucaGen (Novo Nordisk, Bagsværd, DK)
  • Use of medications that are known to cause QT interval prolongation
  • Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods
  • Females who have different basal insulin pattern depending on their menstrual cycle
  • 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): NCT04098549


Locations
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Denmark
Steno Diabetes Center Copenhagen
Gentofte, Denmark, 2820
Sponsors and Collaborators
Steno Diabetes Center Copenhagen
University of Copenhagen
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Responsible Party: Steno Diabetes Center Copenhagen
ClinicalTrials.gov Identifier: NCT04098549    
Other Study ID Numbers: H-19034585
First Posted: September 23, 2019    Key Record Dates
Last Update Posted: June 25, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol

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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
Glucose Metabolism
Hypoglycemia
Glucagon
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Metabolic Diseases
Glucose Metabolism Disorders
Hypoglycemia
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases