Clinical trial NCT03932630: Looping Whilst Restricting Carbohydrates
Official title: Looping Whilst Restricting Carbohydrates (LINEAR) - a Randomised Two-Period Crossover Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Diabetes
Type 1 Diabetes
Keywords: artificial pancreas
hybrid closed-loop
low carbohydrate diet
glucose control
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2019-05-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To investigate the efficacy, safety and utility of hybrid closed-loop glucose control during a low carbohydrate vs. iso-energetic balanced diet in individuals with type 1 diabetes.

Detailed description: Closed-loop systems combining an insulin pump, a glucose sensor and a dosing algorithm that adjusts insulin delivery in a glucose-responsive manner achieve significantly better glucose control than conventional therapy in type 1 diabetes. Achieving satisfactory postprandial glucose control, however, continues to be challenging. The main limitation is the delayed pharmacokinetics and -dynamics of subcutaneously administered insulin with peak actions between 1 and 2 hours. Conversely, glucose levels typically rise within 10minutes following carbohydrate intake. This mismatch largely explains the inability of current closed-loop systems to control postprandial glucose excursions and the increased risk of late postprandial hypoglycaemia in response to both user-derived meal bolus administration and reactive algorithm-driven insulin infusion.

Restricting carbohydrate may therefore significantly improve post-prandial glucose control whilst reducing hypoglycaemia. The efficacy of hybrid closed-loop operation in individuals with type 1 diabetes adhering to a low carbohydrate compared to a iso-caloric balanced diet has not been investigated to date.

Eligibility criteria: Inclusion Criteria:

* Female and male subjects aged 18 years or older
* Diabetes mellitus Type 1 as definded by WHO for at least 2 years or C-peptide negative (\<100 pmol/L with concomitant blood glucose \> 4 mmol/L)
* hybrid-closed-loop Insulin therapy (Minimed 670G) for at least 2 months
* HbA1c \<= 9 %
* The subject is willing and capable of adhering to the diet plan.

Exclusion Criteria:

* Physical or psychological condition likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator.
* Excess alcohol consumption (\> 3 units/day for men, \> 2 units/day for women)
* Pregnancy, planned pregnancy or breast feeding
* Current participation in another clinical trial
* Total daily insulin dose \>2 IU/kg/day
* Nephrolithiasis
* Hereditary dyslipidemia
* Liver steatosis

Primary outcomes:
measure: Percentage of time in target glucose range (3.9 - 10.0 mmol/L)
timeFrame: 2 weeks
Secondary outcomes:
measure: Percentage of time above target (>10 mmol/L)
timeFrame: 2 weeks
measure: Percentage of time below target (<3.9 mmol/L)
timeFrame: 2 weeks
measure: Percentage of time in hypoglycemia (<3.0 mmol/L)
timeFrame: 2 weeks
measure: Hypoglycemia burden quantified as the area under the curve (AUC) with glucose < 3 mmol/L
timeFrame: 2 weeks
measure: Percentage of time in hyperglycemia (>16.7 mmol/L)
timeFrame: 2 weeks
measure: Mean glucose levels (mmol/l)
timeFrame: 2 weeks
measure: Total daily insulin dose (U)
timeFrame: 2 weeks
measure: Daily manual bolus Insulin dose (U)
timeFrame: 2 weeks
measure: 2 hour postprandial glucose increment (mmol/)
timeFrame: 2 weeks
measure: Within-day standard deviation of glucose (mmol/l)
timeFrame: 2 weeks
measure: Within day coefficient of variation of glucose (%)
timeFrame: 2 weeks
measure: Between days coefficient of variation of glucose (%)
timeFrame: 2 weeks
measure: Night-time percentage of time in target glucose range (3.9 - 10.0 mmol/L)
timeFrame: Between 00:00-06:00 over 2 weeks
measure: Night-time percentage of time above target (> 10.0 mmol/L)
timeFrame: Between 00:00-06:00 over 2 weeks
measure: Night-time percentage of time below target (< 3.9 mmol/L)
timeFrame: Between 00:00-06:00 over 2 weeks
measure: Night-time percentage of time in hypoglycemia (< 3.0 mmol/L)
timeFrame: Between 00:00-06:00 over 2 weeks
measure: Night-time percentage of time in hyperglycemia (> 16.7 mmol/L)
timeFrame: Between 00:00-06:00 over 2 weeks
measure: Night-time mean glucose levels
timeFrame: Between 00:00-06:00 over 2 weeks
measure: Within night-time standard deviation of glucose (mmol/l)compared to within daytime period (06: - 24:00) standard deviation of glucose (mmol/l)
timeFrame: Between 00:00-06:00 over 2 weeks
measure: Within nighttime coefficient of variation of glucose(%)
timeFrame: Between 00:00-06:00 over 2 weeks
measure: Change from baseline in lipid profile
timeFrame: 2 weeks
measure: Total daily calorie intake (kcal/day)
timeFrame: 2 weeks
measure: Mean beta-hydroxy butyrate level
timeFrame: 2 weeks
measure: Change from baseline in fasting plasma metabolome
timeFrame: 2 weeks
measure: Incidence of (serious) adverse events
timeFrame: 12 weeks
measure: Percentage of time when pump was in Auto-mode
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: University Department of Endocrinology, Diabetology, Clinical Nutrition and Metabolism
Study officials:
affiliation: Inselspital, Bern University Hospital, University of Bern
name: Lia Bally, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: