Looping Whilst Restricting Carbohydrates

Diabetes Clinical Trial

— LINEAR  

Official title:

Looping Whilst Restricting Carbohydrates (LINEAR) - a Randomised Two-Period Crossover Trial

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03932630
• Other study ID #: LINEAR
• Status: Withdrawn
• Phase: N/A
• Start date: December 2019
• Est. completion date: December 2020

Study information

• Verified date: December 2022
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2020
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Type 1 Diabetes

Intervention

Other:
• Low carbohydrate diet
The study intervention will be an eucaloric low carbohydrate diet (15-20 % of carbohydrates) for 2 weeks.
• balanced diet
The control intervention will be a energy-matched balanced diet (50 % of carbohydrates) for 2 weeks.

Locations

Country	Name	City	State
Switzerland	University Department of Endocrinology, Diabetology, Clinical Nutrition and Metabolism	Bern

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of time in target glucose range (3.9 - 10.0 mmol/L)	The percentage of time in target glucose range will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Percentage of time above target (>10 mmol/L)	The percentage of time below target (>10 mmol/L) will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Percentage of time below target (<3.9 mmol/L)	The percentage of time below target (<3.9 mmol/L) will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Percentage of time in hypoglycemia (<3.0 mmol/L)	The percentage of time in hypoglycemia (<3.0 mmol/L) will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Hypoglycemia burden quantified as the area under the curve (AUC) with glucose < 3 mmol/L	Hypoglycemia burden will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Percentage of time in hyperglycemia (>16.7 mmol/L)	The percentage of time in hyperglycemia (>16.7 mmol/L) will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Mean glucose levels (mmol/l)	Mean sensor glucose levels will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Total daily insulin dose (U)	Total daily insulin dose will be recorded by the insulin pump	2 weeks
Secondary	Daily manual bolus Insulin dose (U)	Daily manual bolus insulin dose will be recorded by the insulin pump	2 weeks
Secondary	2 hour postprandial glucose increment (mmol/)	2 hour postprandial glucose increment will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Within-day standard deviation of glucose (mmol/l)	Within-day standard deviation of glucose will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Within day coefficient of variation of glucose (%)	Within day coefficient of variation of glucose will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Between days coefficient of variation of glucose (%)	Between days coefficient of variation of glucose will be assessed using continuous glucose monitoring (CGM).	2 weeks
Secondary	Night-time percentage of time in target glucose range (3.9 - 10.0 mmol/L)	Percentage of time in target glucose range will be assessed using continuous glucose monitoring (CGM).	Between 00:00-06:00 over 2 weeks
Secondary	Night-time percentage of time above target (> 10.0 mmol/L)	Percentage of time above target will be assessed using continuous glucose monitoring (CGM).	Between 00:00-06:00 over 2 weeks
Secondary	Night-time percentage of time below target (< 3.9 mmol/L)	Percentage of time below target will be assessed using continuous glucose monitoring (CGM).	Between 00:00-06:00 over 2 weeks
Secondary	Night-time percentage of time in hypoglycemia (< 3.0 mmol/L)	Percentage of time in hypoglycemia will be assessed using continuous glucose monitoring (CGM).	Between 00:00-06:00 over 2 weeks
Secondary	Night-time percentage of time in hyperglycemia (> 16.7 mmol/L)	Percentage of time in hyperglycemia will be assessed using continuous glucose monitoring (CGM).	Between 00:00-06:00 over 2 weeks
Secondary	Night-time mean glucose levels	Mean sensor glucose levels will be assessed using continuous glucose monitoring (CGM).	Between 00:00-06:00 over 2 weeks
Secondary	Within night-time standard deviation of glucose (mmol/l)compared to within daytime period (06: - 24:00) standard deviation of glucose (mmol/l)	Standard deviation of glucose will be assessed using continuous glucose monitoring (CGM).	Between 00:00-06:00 over 2 weeks
Secondary	Within nighttime coefficient of variation of glucose(%)	Coefficient of variation of glucose (%) will be assessed using continuous glucose monitoring (CGM).	Between 00:00-06:00 over 2 weeks
Secondary	Change from baseline in lipid profile	Plasma Lipid profile (total Cholesterol, LDL-Cholesterol, HDL-Cholesterol, Triglycerides)	2 weeks
Secondary	Total daily calorie intake (kcal/day)	Total daily calorie intake will be assessed based on photo-documentation of dietary intake	2 weeks
Secondary	Mean beta-hydroxy butyrate level	based on download of blood Ketone meter	2 weeks
Secondary	Change from baseline in fasting plasma metabolome	Fasting serum sampling	2 weeks
Secondary	Incidence of (serious) adverse events	Incidence of severe hypoglycaemia, signficant hyperglycaemia with ketonemia, other SAEs, adverse events, adverse defice effects and device deficiencies	12 weeks
Secondary	Percentage of time when pump was in Auto-mode	Based on pump data download	2 weeks