Looping Whilst Restricting Carbohydrates (LINEAR)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Diabetes; Type 1 Diabetes
• Intervention / Treatment: Other: Low carbohydrate diet; Other: balanced diet

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • University Department of Endocrinology, Diabetology, Clinical Nutrition and Metabolism

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study intervention	Other: Low carbohydrate diet; The study intervention will be an eucaloric low carbohydrate diet (15-20 % of carbohydrates) for 2 weeks.
Active Comparator: Control intervention	Other: balanced diet; The control intervention will be a energy-matched balanced diet (50 % of carbohydrates) for 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Mean glucose levels (mmol/l)	Mean sensor glucose levels will be assessed using continuous glucose monitoring (CGM).	2 weeks
Total daily insulin dose (U)	Total daily insulin dose will be recorded by the insulin pump	2 weeks
Daily manual bolus Insulin dose (U)	Daily manual bolus insulin dose will be recorded by the insulin pump	2 weeks
2 hour postprandial glucose increment (mmol/)	2 hour postprandial glucose increment will be assessed using continuous glucose monitoring (CGM).	2 weeks
Within-day standard deviation of glucose (mmol/l)	Within-day standard deviation of glucose will be assessed using continuous glucose monitoring (CGM).	2 weeks
Within day coefficient of variation of glucose (%)	Within day coefficient of variation of glucose will be assessed using continuous glucose monitoring (CGM).	2 weeks
Between days coefficient of variation of glucose (%)	Between days coefficient of variation of glucose will be assessed using continuous glucose monitoring (CGM).	2 weeks
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
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
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
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
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
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
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
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
Change from baseline in lipid profile	Plasma Lipid profile (total Cholesterol, LDL-Cholesterol, HDL-Cholesterol, Triglycerides)	2 weeks
Total daily calorie intake (kcal/day)	Total daily calorie intake will be assessed based on photo-documentation of dietary intake	2 weeks
Mean beta-hydroxy butyrate level	based on download of blood Ketone meter	2 weeks
Change from baseline in fasting plasma metabolome	Fasting serum sampling	2 weeks
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
Percentage of time when pump was in Auto-mode	Based on pump data download	2 weeks

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: April 28, 2019
• First Submitted That Met QC Criteria: April 28, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): December 19, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: artificial pancreas; glucose control; low carbohydrate diet; hybrid closed-loop
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: LINEAR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No