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出境医 / 临床实验 / Looping Whilst Restricting Carbohydrates (LINEAR)
Looping Whilst Restricting Carbohydrates (LINEAR)
Study Description
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Diabetes Type 1 Diabetes | Other: Low carbohydrate diet Other: balanced diet | Not Applicable |
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 Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 15 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Looping Whilst Restricting Carbohydrates (LINEAR) - a Randomised Two-Period Crossover Trial |
| Actual Study Start Date : | December 11, 2019 |
| Estimated Primary Completion Date : | December 31, 2020 |
| Estimated Study Completion Date : | December 31, 2020 |
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures :
- Percentage of time in target glucose range (3.9 - 10.0 mmol/L) [ Time Frame: 2 weeks ]The percentage of time in target glucose range will be assessed using continuous glucose monitoring (CGM).
Secondary Outcome Measures :
- Percentage of time above target (>10 mmol/L) [ Time Frame: 2 weeks ]The percentage of time below target (>10 mmol/L) will be assessed using continuous glucose monitoring (CGM).
- Percentage of time below target (<3.9 mmol/L) [ Time Frame: 2 weeks ]The percentage of time below target (<3.9 mmol/L) will be assessed using continuous glucose monitoring (CGM).
- Percentage of time in hypoglycemia (<3.0 mmol/L) [ Time Frame: 2 weeks ]The percentage of time in hypoglycemia (<3.0 mmol/L) will be assessed using continuous glucose monitoring (CGM).
- Hypoglycemia burden quantified as the area under the curve (AUC) with glucose < 3 mmol/L [ Time Frame: 2 weeks ]Hypoglycemia burden will be assessed using continuous glucose monitoring (CGM).
- Percentage of time in hyperglycemia (>16.7 mmol/L) [ Time Frame: 2 weeks ]The percentage of time in hyperglycemia (>16.7 mmol/L) will be assessed using continuous glucose monitoring (CGM).
- Mean glucose levels (mmol/l) [ Time Frame: 2 weeks ]Mean sensor glucose levels will be assessed using continuous glucose monitoring (CGM).
- Total daily insulin dose (U) [ Time Frame: 2 weeks ]Total daily insulin dose will be recorded by the insulin pump
- Daily manual bolus Insulin dose (U) [ Time Frame: 2 weeks ]Daily manual bolus insulin dose will be recorded by the insulin pump
- 2 hour postprandial glucose increment (mmol/) [ Time Frame: 2 weeks ]2 hour postprandial glucose increment will be assessed using continuous glucose monitoring (CGM).
- Within-day standard deviation of glucose (mmol/l) [ Time Frame: 2 weeks ]Within-day standard deviation of glucose will be assessed using continuous glucose monitoring (CGM).
- Within day coefficient of variation of glucose (%) [ Time Frame: 2 weeks ]Within day coefficient of variation of glucose will be assessed using continuous glucose monitoring (CGM).
- Between days coefficient of variation of glucose (%) [ Time Frame: 2 weeks ]Between days coefficient of variation of glucose will be assessed using continuous glucose monitoring (CGM).
- Night-time percentage of time in target glucose range (3.9 - 10.0 mmol/L) [ Time Frame: Between 00:00-06:00 over 2 weeks ]Percentage of time in target glucose range will be assessed using continuous glucose monitoring (CGM).
- Night-time percentage of time above target (> 10.0 mmol/L) [ Time Frame: Between 00:00-06:00 over 2 weeks ]Percentage of time above target will be assessed using continuous glucose monitoring (CGM).
- Night-time percentage of time below target (< 3.9 mmol/L) [ Time Frame: Between 00:00-06:00 over 2 weeks ]Percentage of time below target will be assessed using continuous glucose monitoring (CGM).
- Night-time percentage of time in hypoglycemia (< 3.0 mmol/L) [ Time Frame: Between 00:00-06:00 over 2 weeks ]Percentage of time in hypoglycemia will be assessed using continuous glucose monitoring (CGM).
- Night-time percentage of time in hyperglycemia (> 16.7 mmol/L) [ Time Frame: Between 00:00-06:00 over 2 weeks ]Percentage of time in hyperglycemia will be assessed using continuous glucose monitoring (CGM).
- Night-time mean glucose levels [ Time Frame: Between 00:00-06:00 over 2 weeks ]Mean sensor glucose levels will be assessed using continuous glucose monitoring (CGM).
- Within night-time standard deviation of glucose (mmol/l)compared to within daytime period (06: - 24:00) standard deviation of glucose (mmol/l) [ Time Frame: Between 00:00-06:00 over 2 weeks ]Standard deviation of glucose will be assessed using continuous glucose monitoring (CGM).
- Within nighttime coefficient of variation of glucose(%) [ Time Frame: Between 00:00-06:00 over 2 weeks ]Coefficient of variation of glucose (%) will be assessed using continuous glucose monitoring (CGM).
- Change from baseline in lipid profile [ Time Frame: 2 weeks ]Plasma Lipid profile (total Cholesterol, LDL-Cholesterol, HDL-Cholesterol, Triglycerides)
- Total daily calorie intake (kcal/day) [ Time Frame: 2 weeks ]Total daily calorie intake will be assessed based on photo-documentation of dietary intake
- Mean beta-hydroxy butyrate level [ Time Frame: 2 weeks ]based on download of blood Ketone meter
- Change from baseline in fasting plasma metabolome [ Time Frame: 2 weeks ]Fasting serum sampling
- Incidence of (serious) adverse events [ Time Frame: 12 weeks ]Incidence of severe hypoglycaemia, signficant hyperglycaemia with ketonemia, other SAEs, adverse events, adverse defice effects and device deficiencies
- Percentage of time when pump was in Auto-mode [ Time Frame: 2 weeks ]Based on pump data download
Eligibility Criteria
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Contacts
| Contact: Lia Bally, MD PhD | +41 (0)31 632 36 77 | lia.bally@insel.ch |
Locations
| Switzerland | |
| University Department of Endocrinology, Diabetology, Clinical Nutrition and Metabolism | Recruiting |
| Bern, Switzerland, 3010 | |
| Contact: Lia Bally, MD PhD | |
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
| Principal Investigator: | Lia Bally, MD PhD | Inselspital, Bern University Hospital, University of Bern |
| Tracking Information | |||||||
|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | April 28, 2019 | ||||||
| First Posted Date ICMJE | May 1, 2019 | ||||||
| Last Update Posted Date | December 17, 2019 | ||||||
| Actual Study Start Date ICMJE | December 11, 2019 | ||||||
| Estimated Primary Completion Date | December 31, 2020 (Final data collection date for primary outcome measure) | ||||||
| Current Primary Outcome Measures ICMJE |
Percentage of time in target glucose range (3.9 - 10.0 mmol/L) [ Time Frame: 2 weeks ] The percentage of time in target glucose range will be assessed using continuous glucose monitoring (CGM).
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||
| Change History | |||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||
| Descriptive Information | |||||||
| Brief Title ICMJE | Looping Whilst Restricting Carbohydrates | ||||||
| Official Title ICMJE | Looping Whilst Restricting Carbohydrates (LINEAR) - a Randomised Two-Period Crossover Trial | ||||||
| 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. |
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| Study Type ICMJE | Interventional | ||||||
| Study Phase ICMJE | Not Applicable | ||||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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| Condition ICMJE |
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| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||
| Recruitment Status ICMJE | Recruiting | ||||||
| Estimated Enrollment ICMJE |
15 | ||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||
| Estimated Study Completion Date ICMJE | December 31, 2020 | ||||||
| Estimated Primary Completion Date | December 31, 2020 (Final data collection date for primary outcome measure) | ||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | Switzerland | ||||||
| Removed Location Countries | |||||||
| Administrative Information | |||||||
| NCT Number ICMJE | NCT03932630 | ||||||
| Other Study ID Numbers ICMJE | LINEAR | ||||||
| Has Data Monitoring Committee | No | ||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE | Not Provided | ||||||
| Responsible Party | Lia Bally, University Hospital Inselspital, Berne | ||||||
| Study Sponsor ICMJE | University Hospital Inselspital, Berne | ||||||
| Collaborators ICMJE | Not Provided | ||||||
| Investigators ICMJE |
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| PRS Account | University Hospital Inselspital, Berne | ||||||
| Verification Date | December 2019 | ||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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