The Effect of Rapid and Slow Glucose Fall on the Subsequent Glucose Production in People With Type 1 Diabetes

Type 1 Diabetes Clinical Trial

— RaSlo-19  

Official title:

The Effect of Rapid and Slow Glucose Fall on the Subsequent Glucose Production in People With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04098549
• Other study ID #: H-19034585
• Status: Completed
• Phase: N/A
• Start date: September 12, 2019
• Est. completion date: January 15, 2020

Study information

• Verified date: June 2020
• Source: Steno Diabetes Center Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 15, 2020
• Est. primary completion date: January 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Blood Glucose, Low
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Glucose Metabolism Disorders
• Hypoglycemia
• Metabolic Diseases
• Type 1 Diabetes

Intervention

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

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center Copenhagen	Gentofte

Sponsors (2)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen	University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive incremental area under the glucose curve (PI-AUC) (using the plasma glucose concentration before glucagon administration as basal level)		from 0-120 minutes after glucagon administration
Secondary	Total area under the glucose curve (AUC)		from 0-120 minutes after glucagon administration
Secondary	Peak plasma glucose		from 0-120 minutes after glucagon administration
Secondary	Incremental plasma glucose peak		from 0-120 minutes after glucagon administration
Secondary	Time-to-peak plasma glucose		from 0-120 minutes after glucagon administration
Secondary	Plasma glucose level		120 minutes after glucagon administration
Secondary	Duration of plasma glucose above 4.0 mmol/l		from 0-120 minutes after glucagon administration
Secondary	Duration of plasma glucose above baseline		from 0-120 minutes after glucagon administration
Secondary	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		throughout phase 4 (until 120 minutes after glucagon administration)
Secondary	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		throughout phase 4 (until 120 minutes after glucagon administration)
Secondary	Time from glucagon administration to reaching a plasma glucose level > 3,9 mmol/l		from 0-120 minutes after glucagon administration
Secondary	Duration of a plasma glucose level in the range of 3.9-10 mmol/l		from 0-120 minutes after glucagon administration
Secondary	Duration of a plasma glucose level in the range of 3.9-7.8 mmol/l		from 0-120 minutes after glucagon administration
Secondary	Change in insulin levels (measured as area under the curve)		0-120 minutes after glucagon administration
Secondary	Change in insulin levels (measured as peak change)		from baseline to 120 minutes after glucagon administration
Secondary	Change in glucagon levels (measured as area under the curve)		0-120 minutes after glucagon administration
Secondary	Change in glucagon levels (measured as peak change)		0-120 minutes after glucagon administration
Secondary	Average changes in Edinburgh Hypoglycemia Scale		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
Secondary	Average change in visual analogue scale score for nausea, headache, stomach ache and palpitations		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
Secondary	Number of subjects experiencing vomiting		from 0-120 minutes after glucagon administration