The Impact of Subcutaneous Glucagon Before, During and After Exercise a Study in Patients With Type 1 Diabetes Mellitus

NCT ID: NCT02882737

Last Updated: 2017-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2017-07-11

Brief Summary

This project is part of several studies exploring situations, where glucagon potential has lesser glucose elevating effect. Exercise can be one of these situations as exercise may reduce liver glycogen depots.

The investigators aims are:

1. To compare the increase in plasma glucose after 200µg glucagon given either after exercise or after resting for 45 minutes.

2. To determine whether a subcutaneous glucagon injection just before exercise has a greater impact on hepatic glucose production and thereby is superior to an injection after exercise in preventing hypoglycemia during and two hours after exercise.

3. To compare the accuracy of two Dexcom G4 continuous glucose monitors, (CGM) placed at either the abdominal wall or on the upper arm.

Detailed Description

Design:

A randomized placebo-controlled single-blinded study will be conducted. The subjects do not know if they get glucagon or placebo but the investigator know if the subject get glucagon or placebo. Study participants have to complete three study days and serve as their own controls. After participants have given an informed consent, they will go through three steps:

1. Screening day

2. Run-in period

3. Three study days in a random order:

• Exercise and glucagon injected after cycling/or during cycling in case of hypoglycemia
• Resting and glucagon after resting
• Exercise and glucagon subcutaneous before cycling

47-49 hours before the study visits one CGM device is placed on the abdominal wall on the participant at least 7 cm from the site of the insulin pump infusion set. One CGM is placed on the non-dominant upper arm between 10 cm from elbow and 10 cm from shoulder on the posterior/lateral side on the arm. The CGMs will be in place for seven days. The CGM readings on the CGM placed at the abdominal wall are not blinded for the participant. The CGM readings on the CGM placed on the arm is blinded for the participant. In the period from the study visits to 4 days after the study visits the participant will do self-monitoring of blood glucose 8 times a day on standardized times.

Conditions

Type 1 Diabetes Mellitus

Study Design

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

Study Groups

Exercise and glucagon before exercise

120 minutes after breakfast; a single subcutaneous bolus of 200µg glucagon is administered by the primary investigator. However, the patient do, not know whether placebo or a glucagon injection is administered.

Exercise: Immediately thereafter, the patient will bicycle for 45 minutes at 50% of the heart rate HR reserve.

When exercise is ended a single subcutaneous bolus of 0.2 ml saline is administered and the exercise session will be suspended. Again, the patient do not know whether placebo or a glucagon is administered.

Group Type: EXPERIMENTAL

Glucagon before exercise

Intervention Type: DRUG

Exercise and glucagon after exercise

120 minutes after breakfast; a single subcutaneous bolus of 0.2 ml saline is administered by the primary investigator. However, the patient do, not know whether placebo or a glucagon injection is administered.

Exercise: Immediately thereafter, the patient will bicycle for 45 minutes at 50% of the heart rate HR reserve.

Low-dose glucagon phase: When exercise is ended or when hypoglycemia occurs (≤3.9 mmol/l); a single subcutaneous bolus of 200μg glucagon is administered and the exercise session will be suspended. Again, the patient do not know whether placebo or a glucagon is administered.

Group Type: ACTIVE_COMPARATOR

Glucagon after exercise

Intervention Type: DRUG

Resting and glucagon after resting

120 minutes after breakfast; a single subcutaneous bolus of 200μg placebo is administered.

Resting: After placebo injection the patient will be resting on a hospital bed for 45 minutes. The patient do not know if placebo or glucagon is administered.

Low-dose glucagon phase: After 45 minutes of resting or when hypoglycemia occurs, a single subcutaneous bolus of 200μg glucagon is administered.

Safety issues: If plasma glucose drops < 2.5 mmol/l at two consecutive measurements with 5 min interval or the patient experiences unbearable symptoms of hypoglycemia even after glucagon administration, 20 g carbohydrate is given orally. If plasma glucose drops< 2.3 mmol/l or doesn't raise sufficient after oral glucose, we will give intravenøs glucose to the patient. The study will then end and a new study day will be planned.

Group Type: ACTIVE_COMPARATOR

Glucagon after resting

Intervention Type: DRUG

Interventions

Glucagon before exercise

Intervention Type: DRUG

Glucagon after exercise

Intervention Type: DRUG

Glucagon after resting

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Type 1 Diabetes ≥ 2 year
• BMI 20-30 kg/m2
• Insulin pump ≥ 1 year.
• HbA1c < 69 mmol/mol (8.5 %)
• Hypoglycemia awareness (reported by Gold et al.)
• Use of carbohydrate counting and the insulin pump bolus calculator for all meals
• Sedentary or mild physical activity: Less than 150 minutes of moderate-intensity aerobic physical activity throughout the week and less than 75 minutes of vigorous-intensity aerobic physical activity throughout the week .

Exclusion Criteria

• Allergy or intolerance to lactose or GlucaGen® (Novo Nordisk, Bagsværd, DK)
• Impaired renal function (eGFR < 60 ml/min/1.73m2)
• Liver disease with ALAT > 2.5 times the upper limit of the reference interval
• Use of anti-diabetic medicine (other than insulin), per oral corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to study start
• Known or suspected alcohol or drug abuse
• Other concomitant medical or psychological condition that according to the investigator's assessment makes the patient unsuitable for study participation
• Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods
• Inability to understand the patient information and to give informed consent
• Physical or mental incapacity to perform exercise
• Chronic use or unable to stop acetaminophen (paracetamol) use
• Allergy to the patch of CGM

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

Sponsors

Technical University of Denmark

OTHER

Sponsor Role: collaborator

Hvidovre University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Isabelle Steineck

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Isabelle Steineck, MD

Role: PRINCIPAL_INVESTIGATOR

Hvidovre Hospital department of endocrinology

Locations

Isabelle Steineck

Hvidovre, , Denmark

Countries

Denmark

References

Steineck IIK, Ranjan A, Schmidt S, Clausen TR, Holst JJ, Norgaard K. Preserved glucose response to low-dose glucagon after exercise in insulin-pump-treated individuals with type 1 diabetes: a randomised crossover study. Diabetologia. 2019 Apr;62(4):582-592. doi: 10.1007/s00125-018-4807-8. Epub 2019 Jan 14.

Reference Type: DERIVED

PMID: 30643924 (View on PubMed)

Other Identifiers

16016762

Identifier Type: -

Identifier Source: org_study_id