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

NCT02882737 | Completed DMC

• 1 other identifier: 16016762
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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. 1.To compare the increase in plasma glucose after 200µg glucagon given either after exercise or after resting for 45 minutes.
2. 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. 3.To compare the accuracy of two Dexcom G4 continuous glucose monitors, (CGM) placed at either the abdominal wall or on the upper arm.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is peak plasma glucose achieved within 2 hours after the 200 μg subcutaneous glucagon injection. In the primary analysis, the investigators will compare the peak plasma glucose after exercise and after resting.

  2 hours

Secondary Outcomes (24)

• The time-to-peak value after glucagon injection.

  2 hours

• Duration of the glucagon effect; equal to the time point from glucagon injection to when plasma glucose is below baseline.

  2 hours

• The glycaemic effect, calculated as the total area under the curve (tAUC) after each glucagon injection.

  2 hours

• Changes in plasma ketone bodies after each glucagon injection.

  2 hours

• Changes in plasma lactic acid after each glucagon injection

  2 hours

Study Arms (3)

Exercise and glucagon before exercise

EXPERIMENTAL

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.

Drug: Glucagon before exercise

Exercise and glucagon after exercise

ACTIVE COMPARATOR

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.

Drug: Glucagon after exercise

Resting and glucagon after resting

ACTIVE COMPARATOR

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.

Drug: Glucagon after resting

Interventions

Glucagon before exercise DRUG

Exercise and glucagon before exercise

Glucagon after exercise DRUG

Exercise and glucagon after exercise

Glucagon after resting DRUG

Resting and glucagon after resting

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 .

You may not qualify if:

• 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

Sponsors & Collaborators

• Hvidovre University Hospital: lead
• Technical University of Denmark: collaborator

Study Sites (1)

Isabelle Steineck

Hvidovre, 2650, Denmark

Location

Related Publications (1)

• 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.

  PMID: 30643924 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Isabelle Steineck, MD

  Hvidovre Hospital department of endocrinology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 17, 2016
• First Posted: August 30, 2016
• Study Start: September 1, 2016
• Primary Completion: July 11, 2017
• Study Completion: July 11, 2017
• Last Updated: July 24, 2017

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)