DiabetesLINEARNCT03932630
Looping Whilst Restricting Carbohydrates
A study testing Low carbohydrate diet and balanced diet in people with Diabetes and Type 1 Diabetes, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes, Type 1 Diabetes
- What is being tested?
- Low carbohydrate diet and balanced diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteSwitzerland
- Study dates
- Dec 2019to Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Department of Endocrinology, Diabetology, Clinical Nutrition and Metabolism
Bern, 3010
About this study
Official title: 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.
Read the 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.
- Conditions
- Diabetes, Type 1 Diabetes
- Being tested
- Low carbohydrate diet, balanced diet
- Keywords
- artificial pancreas, hybrid closed-loop, low carbohydrate diet, glucose control
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low carbohydrate dietOther
The study intervention will be an eucaloric low carbohydrate diet (15-20 % of carbohydrates) for 2 weeks.
balanced dietOther
The control intervention will be a energy-matched balanced diet (50 % of carbohydrates) for 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Study intervention | Experimental | Not described Receives: Other: Low carbohydrate diet |
| Control intervention | Active comparator | Not described Receives: Other: balanced diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 2 weeks
Secondary outcomes (26)
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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 2 weeks
Mean glucose levels (mmol/l)
Mean sensor glucose levels will be assessed using continuous glucose monitoring (CGM).
Measured: 2 weeks
Total daily insulin dose (U)
Total daily insulin dose will be recorded by the insulin pump
Measured: 2 weeks
Daily manual bolus Insulin dose (U)
Daily manual bolus insulin dose will be recorded by the insulin pump
Measured: 2 weeks
2 hour postprandial glucose increment (mmol/)
2 hour postprandial glucose increment will be assessed using continuous glucose monitoring (CGM).
Measured: 2 weeks
Within-day standard deviation of glucose (mmol/l)
Within-day standard deviation of glucose will be assessed using continuous glucose monitoring (CGM).
Measured: 2 weeks
Within day coefficient of variation of glucose (%)
Within day coefficient of variation of glucose will be assessed using continuous glucose monitoring (CGM).
Measured: 2 weeks
Between days coefficient of variation of glucose (%)
Between days coefficient of variation of glucose will be assessed using continuous glucose monitoring (CGM).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: Between 00:00-06:00 over 2 weeks
Change from baseline in lipid profile
Plasma Lipid profile (total Cholesterol, LDL-Cholesterol, HDL-Cholesterol, Triglycerides)
Measured: 2 weeks
Total daily calorie intake (kcal/day)
Total daily calorie intake will be assessed based on photo-documentation of dietary intake
Measured: 2 weeks
Mean beta-hydroxy butyrate level
based on download of blood Ketone meter
Measured: 2 weeks
Change from baseline in fasting plasma metabolome
Fasting serum sampling
Measured: 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
Measured: 12 weeks
Percentage of time when pump was in Auto-mode
Based on pump data download
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2019
- Study startDec 2019 (estimated)
- Primary completionDec 2020 (estimated)
- Study completionDec 2020 (estimated)
Why it stopped: Due to COVID-19 related challenges and restrictions, the project could not be launched as planned. Meanwhile, the current state of research has changed and the initialisation of the project is no longer appropriate. No participants were recurited.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lia Bally, Insel Gruppe AG, University Hospital Bern
- Investigators
- Lia Bally, MD PhD, Principal investigator, Inselspital, Bern University Hospital, University of Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03932630
- Sponsor's protocol ID
- LINEAR
- Acronym
- LINEAR
- Status last verified
- Dec 2022
- First submitted
- 28 Apr 2019
- Last updated
- 19 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Looping Whilst Restricting Carbohydrates (LINEAR) - a Randomised Two-Period Crossover Trial
- ClinicalTrials.gov ID
- NCT03932630
- Acronym / sponsor ID
- LINEAR / LINEAR
- Conditions
- Diabetes, Type 1 Diabetes
- Keywords
- artificial pancreas, hybrid closed-loop, low carbohydrate diet, glucose control
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to COVID-19 related challenges and restrictions, the project could not be launched as planned. Meanwhile, the current state of research has changed and the initialisation of the project is no longer appropriate. No participants were recurited.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- Dec 2019 (estimated)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 1 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study intervention | Experimental | Other: Low carbohydrate diet |
| Control intervention | Active comparator | Other: balanced diet |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low carbohydrate dietThe study intervention will be an eucaloric low carbohydrate diet (15-20 % of carbohydrates) for 2 weeks. | Other | Study intervention |
| balanced dietThe control intervention will be a energy-matched balanced diet (50 % of carbohydrates) for 2 weeks. | Other | Control intervention |
Primary outcome
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).
26 secondary outcomes
Percentage of time above target (>10 mmol/L)
Time frame: 2 weeks
Percentage of time below target (<3.9 mmol/L)
Time frame: 2 weeks
Percentage of time in hypoglycemia (<3.0 mmol/L)
Time frame: 2 weeks
Hypoglycemia burden quantified as the area under the curve (AUC) with glucose < 3 mmol/L
Time frame: 2 weeks
Percentage of time in hyperglycemia (>16.7 mmol/L)
Time frame: 2 weeks
Mean glucose levels (mmol/l)
Time frame: 2 weeks
Total daily insulin dose (U)
Time frame: 2 weeks
Daily manual bolus Insulin dose (U)
Time frame: 2 weeks
2 hour postprandial glucose increment (mmol/)
Time frame: 2 weeks
Within-day standard deviation of glucose (mmol/l)
Time frame: 2 weeks
Within day coefficient of variation of glucose (%)
Time frame: 2 weeks
Between days coefficient of variation of glucose (%)
Time frame: 2 weeks
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
Night-time percentage of time above target (> 10.0 mmol/L)
Time frame: Between 00:00-06:00 over 2 weeks
Night-time percentage of time below target (< 3.9 mmol/L)
Time frame: Between 00:00-06:00 over 2 weeks
Night-time percentage of time in hypoglycemia (< 3.0 mmol/L)
Time frame: Between 00:00-06:00 over 2 weeks
Night-time percentage of time in hyperglycemia (> 16.7 mmol/L)
Time frame: Between 00:00-06:00 over 2 weeks
Night-time mean glucose levels
Time frame: 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)
Time frame: Between 00:00-06:00 over 2 weeks
Within nighttime coefficient of variation of glucose(%)
Time frame: Between 00:00-06:00 over 2 weeks
Change from baseline in lipid profile
Time frame: 2 weeks
Total daily calorie intake (kcal/day)
Time frame: 2 weeks
Mean beta-hydroxy butyrate level
Time frame: 2 weeks
Change from baseline in fasting plasma metabolome
Time frame: 2 weeks
Incidence of (serious) adverse events
Time frame: 12 weeks
Percentage of time when pump was in Auto-mode
Time frame: 2 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lia Bally, MD PhD principal investigator
Inselspital, Bern University Hospital, University of Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low carbohydrate diet and balanced diet in people with Diabetes and Type 1 Diabetes, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of time in target glucose range (3.9 - 10.0 mmol/L) (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2022.