Clinical trial NCT03497260: Fructose in Exercising Individuals With Type 1 Diabetes Using Insulin Degludec
Official title: Fructose to Reduce Exercise-associated Hypoglycaemia in Individuals With Type 1 Diabetes Treated With Insulin Degludec: Questioning a Paradigm and Offering a Novel Strategy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Diabetes Complications
Keywords: Type 1 Diabetes, Fructose, Exercise, Hypoglycaemia, Degludec
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2018-04-13
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: To determine and compare the time-to-hypoglycaemia (defined as plasma glucose \<3.9mmol/L) in individuals with type 1 diabetes treated with ultra-Long acting insulin degludec during aerobic exercise with or without prior ingestion of a single oral fructose load.

Detailed description: Glycaemic control remains complex and demanding during exercise for type 1 diabetes (T1D) patients. Traditional treatment guidelines for exercise emphasizing the reduction of insulin doses and/or ingestion of additional carbohydrates are of limited applicability for patients treated with ultra-long acting basal insulin analogues. Dose reductions may require two to three days for modern basal insulin analogues in order to achieve an adapted steady state, hereby increasing the risk of inadequate insulin-following exercise. If T1D patients engage in recreational exercise - as recommended by every international treatment guideline - current treatment strategies may simply not be sufficient.

As a consequence for patients treated with modern basal insulin analogues, it seems more adequate not to modify insulin doses but to apply alternative strategies for recreational exercise. The ingestion of fructose, an insulin-independent carbohydrate, which increases lipid oxidation but attenuates the dependency on carbohydrates may offer a novel strategy. Up to date, only preliminary data for fructose have been produced regarding clinical effectiveness and underlying mechanisms in the prevention of hypoglycaemia. The present comprehensive study aims to investigate the clinical efficacy, feasibility, and safety of a pre-exercise oral fructose load without modification of insulin degludec in T1D patients.

Eligibility criteria: Inclusion Criteria:

* Type 1 diabetes as defined by the World Health Organization (WHO) for at least 1 year or confirmed negative C-peptide (\<100pmol/l with concomitant blood glucose \>4 mmol/l)
* Male subjects aged between 18-45 years
* HbA1c \<8.0% (64mmol/mol) based on analysis from the central laboratory unit of the University Hospital Bern.
* Basal/Bolus-insulin regimen with insulin degludec for at least 3 months, with good knowledge of insulin self-management
* Regular physical activity (at least 30 min of moderate exercise 3 times weekly)
* Written informed consent

Exclusion Criteria:

* Relevant diabetic complications as judged by the investigator
* Total daily insulin dose \>2 IU/kg/day
* Hypoglycaemia unawareness (Gold score \> 4) or any episode of severe hypoglycaemia as defined by the American Diabetes Association within the last 6 months
* Physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
* Current treatment with drugs known to interfere with metabolism, e.g. systemic corticosteroids, statins etc.
* Known fructose-intolerance or malabsorption
* Known allergy to one of the study drugs

Primary outcomes:
measure: Time (in minutes) to hypoglycaemia (plasma glucose <3.9mmol/l)
timeFrame: From time point 0 minutes (initiation of exercise) to time point 60 minutes (completion of exercise) or development of hypoglycaemia
Secondary outcomes:
measure: Glucose levels before exercise
timeFrame: Time point -30 minutes until time point 0 minutes (initiation of exercise)
measure: Glucose levels during exercise
timeFrame: From time point 0 minutes until time point 60 minutes (completion of exercise) or development of hypoglycaemia
measure: Glucose levels after exercise
timeFrame: From time point 0 minutes until time point 90 minutes
measure: Lactate levels before exercise
timeFrame: From time point -30 minutes until time point 0 minutes (initiation of exercise)
measure: Lactate levels during exercise
timeFrame: From time point 0 minutes until time point 60 minutes (completion of exercise) or development of hypoglycaemia
measure: Lactate levels after exercise
timeFrame: From time point 0 minutes until time point 90 minutes
measure: Insulin levels before exercise
timeFrame: Time point -30 minutes until time point 0 minutes (initiation of exercise)
measure: Insulin levels during exercise
timeFrame: From time point 0 minutes until time point 60 minutes (completion of exercise) or development of hypoglycaemia
measure: Insulin levels after exercise
timeFrame: From time point 0 minutes until time point 150 minutes
measure: Heart rate before exercise
timeFrame: Time point -30 minutes until time point 0 minutes (initiation of exercise)
measure: Heart rate during exercise
timeFrame: From time point 0 minutes until time point 60 minutes (completion of exercise) or development of hypoglycaemia
measure: Oxygen consumption before exercise
timeFrame: Between 15 minutes and 5 minutes before initiation of exercise
measure: Oxygen consumption during exercise
timeFrame: Between 15 minutes and 20 minutes during exercise
measure: Carbon dioxide production before exercise
timeFrame: Between 15 minutes and 5 minutes before initiation of exercise
measure: Carbon dioxide production during exercise
timeFrame: Between 15 minutes and 20 minutes during exercise
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Division of Endocrinology, Diabetes and Clinical Nutrition, Bern University Hospital
Study officials:
affiliation: Inselspital, Bern University Hospital, University of Bern
name: Christoph Stettler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kosinski C, Herzig D, Laesser CI, Nakas CT, Melmer A, Vogt A, Vogt B, Laimer M, Bally L, Stettler C. A Single Load of Fructose Attenuates the Risk of Exercise-Induced Hypoglycemia in Adults With Type 1 Diabetes on Ultra-Long-Acting Basal Insulin: A Randomized, Open-Label, Crossover Proof-of-Principle Study. Diabetes Care. 2020 Sep;43(9):2010-2016. doi: 10.2337/dc19-2250. Epub 2020 Jun 26.