Type 1 DiabetesNCT04758858
Carbohydrates Under Target for Type 1 Diabetes Management
A study testing Insulin treatment optimization with participant's usual diet, Abbott's FreeStyle Libre and Three-day food journal in people with Type 1 Diabetes, run by Institut de Recherches Cliniques de Montreal at 1 site in Canada.
Trial summary
Recently, there has been an increased interest in limiting carbohydrates (CHO) intakes for improving long-term health. Low CHO (<30% energy from CHO) and very low CHO high fat (VLCHF; 10% CHO, 75% Lipid) diets are being advocated among people living with diabetes given their almost immediate favorable impact on… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Insulin treatment optimization with participant's usual diet, Abbott's FreeStyle Libre and Three-day food journal
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2021to Mar 2023
- 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
- Men and women > 18 years old
- Duration of T1D > 12 months
- On intensive insulin therapy
- Own a smartphone or tablet to use two mobile applications for nutritional and physical activity tracking: Keenoa and Piezo: Achieve the Guidelines!
Who cannot join
- Already following a low-CHO diet (<30% CHO)
- Type 2 diabetes or other form of diabetes
- Known gastroparesis (clinical diagnosis)
- Advanced kidney disease (eGFR < 50 mL/min)
- Known significant liver disease (e.g. cirrhosis, active hepatitis, liver transplantation)
- Recent (<6 months) major cardiovascular event (e.g. myocardial infarction, cerebrovascular accident, major revascularization, etc.)
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- Pregnancy (ongoing or planned in the next 6 months)
- Breastfeeding (ongoing)
- Recent severe hypoglycemia episodes (BG <2.8 mmol/L or assistance from a third party) or ketoacidosis (<6 weeks)
- Claustrophobia or presence of metal devices/implants in the body
- Recent (<6 weeks) or planned (next 6 months) modification in insulin treatment
- Recent (<6 weeks) or planned (next 6 months) modification in cardiometabolic drugs for blood pressure and/or lipids. These drugs must remain stable all along the trial
- Off label adjunct therapy with SGLT-2 inhibitors (Forxiga®, Invokana® or Jardiance®)
- Recent (<6 weeks) or planned (next 6 months) modification of adjunct therapy (Metformin, Glumetza®, Victoza®, Trulicity® and Ozempic®)
Trial locations and contacts
1 site in 1 country.
Canada1 site
Institut de recherches cliniques de Montréal
Montreal, Quebec, H2W 1R7
About this study
Recently, there has been an increased interest in limiting carbohydrates (CHO) intakes for improving long-term health. Low CHO (<30% energy from CHO) and very low CHO high fat (VLCHF; 10% CHO, 75% Lipid) diets are being advocated among people living with diabetes given their almost immediate favorable impact on post-prandial blood glucose levels and on hemoglobin A1c that have been reported by users. Adoption of these diets are met with reluctance by healthcare professionals due to the lack of information on their safety. Concerns include the impact on hypoglycemia frequency and glucagon response to hypoglycemia, diabetic ketoacidosis, lipid profile, liver function insulin dose adjustments when adopting them in the context of type 1 diabetes (T1D). Through a series of interviews, people with diabetes following a VLCHF reported that the lack of support from HCPs often leads to hiding the fact that they have adopted a VLCHF diet. This is an important source of concern that can lead to additional safety issues.
The goal is to fill an important knowledge gap about the effectiveness, benefits and risks of low CHO and VLCHF diets for people with T1D. The primary objective is to compare the percentage of TIR of adults with T1D following a low-CHO diet or a VLCHF diet versus a control diet for 12 weeks. The secondary objectives are (1) to evaluate efficacy of glucagon in correcting hypoglycemia in the context of restricted carbohydrates intakes; (2) to evaluate changes in HbA1c at 12 weeks and glucose fluctuations and % of time in hypoglycemia at 6 weeks and 12 weeks of control diet, low-CHO diet or VLCHF diet; (3) to compare key cardiometabolic risk factors (body composition, blood lipids, blood pressure and liver inflammatory markers and function) at 6 weeks and 12 weeks of control diet, low-CHO diet or VLCHF diet; (4) to evaluate the effect of restrictive CHO diets (low-CHO and VLCHF) on the composition of the intestinal microbiota (optional).
- Conditions
- Type 1 Diabetes
- Being tested
- Insulin treatment optimization with participant's usual diet, Abbott's FreeStyle Libre, Three-day food journal, Medical visit, Blood pressure measurements
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin treatment optimization with participant's usual dietOther
Two weeks before the intervention phase, insulin dose optimization and revision of participants' knowledge on carbohydrates counting, hypo- and hyperglycemia prevention and treatment will be done with a nurse and a dietitian under a physician's supervision. Once to twice a week, participants will be contacted to review if glucose values are in target.
Abbott's FreeStyle LibreDevice
During the whole trial, blood glucose will be assessed by intermittent scanning Continuous Glucose Monitors (isCGM; Abbott's Freestyle-Libre glucose sensor). Participants will be asked to record or download, in their Freestyle Libre reader or in their insulin pump, their insulin doses being injected each day.
Three-day food journalOther
Two weeks before the intervention phase, participants will be asked to complete a 3-day food journal, using the Keenoa mobile application, with carbohydrates (CHO) content of food and blood glucose measures to optimize their insulin doses. Analysis of the food journal will allow us to quantify the participants' usual diet.
Medical visitOther
During visit 1, a short medical interview will be done to establish if the subject is eligible to participate in the study. A list of current medications, presence of complications, as well as comorbidities associated with their diabetes will be collected in their medical file during the visit with the endocrinologist.
Blood pressure measurementsOther
Blood pressure (systolic and diastolic blood pressure) will be measured during all visits (visits 1 to 4).
Anthropometric parameters measurementsOther
Weight, height, BMI and waist circumference will be measured during all visits (visits 1 to 4).
Indirect calorimetry testOther
Both resting metabolic rate and respiratory quotient will be measured after a 10-hour fast by indirect calorimetry. The test will be done twice, before (visit 2) and after (visit 4) the intervention phase.
Well-being questionnaireOther
Participants will be asked to complete a well-being questionnaire (nausea, fatigue, etc) during visits 2, 3 and 4.
Diet appreciation questionnaireOther
Participants will be asked to complete a diet appreciation (appetite, fullness, etc) questionnaire during visits 3 and 4.
Pedometer (PiezoRxD)Device
Participants will be asked to wear a pedometer (PiezoRxD) that will record their steps every day during the whole trial. Also, they will have to install Piezo: Achieve the Guidelines!, a free mobile application, on their smartphone or tablet. It will connect to their pedometer via bluetooth and will help the research assistant track their data remotely
Hepatic imaging (MRI)Other
Imaging of participants' liver will be done by MRI at the Centre Hospitalier de l'Université de Montréal (CHUM). The test will be done twice, before (visit 2) and after (visit 4) the intervention phase.
Glucagon efficiency testOther
The glucagon efficiency test will be done twice, before (visit 2) and after (visit 4) the intervention phase. A subcutaneous insulin injection based on individual insulin correction factor will be given to induce hypoglycemia down to 3 mmol/L (based on plasma glucose). A subcutaneous injection of 300 µg of glucagon will be administered.
Body composition : Dual Energy X-ray absorptiometry (DEXA)Other
Lean body mass and fat mass will be measured by Dual Energy X-ray absorptiometry (DEXA). The DEXA test will be done twice, before (visit 2) and after (visit 4) the intervention phase.
Blood testsOther
Blood tests will be done to assess participants' diabetes control as well as to assess other biochemical markers (blood lipids as well as markers of inflammation and liver function). Blood will be collected and analyzed during all visits (visits 1 to 4).
Stool sample collections (optional)Other
Participants will be asked to collect and immediately freeze their stool sample until it is given to the study team (for intestinal microbiota composition analysis). This will be done three times during the study, during phase 1, between week 1 and 6 of phase 2 and between week 6 and 12 of phase 2.
Hypoglycemia journalOther
During the whole trial, participants will be asked to keep a log of their hypoglycemia episodes, which are defined by the need to consume CHO. They will be asked to note the time, symptoms (including time taken for disappearance after treatment), capillary glucose measurement and the amount of CHO consumed.
Ketone journalOther
During the intervention phase, participants will be asked to measure their ß-hydroxybutarate level (mmol/L) with their Abbott's Freestyle-Libre scanner at least twice per week before breakfast. Participants will be asked to check their ketone bodies for sensor or capillary glucose levels exceeding 15 mmol/l, when their sensor indicates high without a specific glucose value and when they have symptoms of ketoacidosis (regardless of glucose reading).
Adherence to the diet (Keenoa)Other
During the whole dietary intervention phase (phase 2), participants will confirm that they have followed their menus by taking before and after pictures of their meals every day and indicating the percentage of their meal consumed (25-50-75-100%) via the Keenoa mobile application.
| Study group | Role | What they receive |
|---|---|---|
| VLCHF (Very Low CHO High Fat) Diet | Active comparator | 10% of energy from CHO, 15% proteins, and 75% lipids Receives: Other: Insulin treatment optimization with participant's usual diet; Device: Abbott's FreeStyle Libre; Other: Three-day food journal; Other: Medical visit; Other: Blood pressure measurements; Other: Anthropometric parameters measurements; Other: Indirect calorimetry test; Other: Well-being questionnaire; Other: Diet appreciation questionnaire; Device: Pedometer (PiezoRxD); Other: Hepatic imaging (MRI); Other: Glucagon efficiency test; Other: Body composition : Dual Energy X-ray absorptiometry (DEXA); Other: Blood tests; Other: Stool sample collections (optional); Other: Hypoglycemia journal; Other: Ketone journal; Other: Adherence to the diet (Keenoa) |
| Low-CHO Diet | Active comparator | 30% of energy from CHO, 15% proteins and 55% lipids Receives: Other: Insulin treatment optimization with participant's usual diet; Device: Abbott's FreeStyle Libre; Other: Three-day food journal; Other: Medical visit; Other: Blood pressure measurements; Other: Anthropometric parameters measurements; Other: Indirect calorimetry test; Other: Well-being questionnaire; Other: Diet appreciation questionnaire; Device: Pedometer (PiezoRxD); Other: Hepatic imaging (MRI); Other: Glucagon efficiency test; Other: Body composition : Dual Energy X-ray absorptiometry (DEXA); Other: Blood tests; Other: Stool sample collections (optional); Other: Hypoglycemia journal; Other: Ketone journal; Other: Adherence to the diet (Keenoa) |
| Control Diet | Placebo comparator | 50% of energy from CHO, 15% proteins and 35% lipids Receives: Other: Insulin treatment optimization with participant's usual diet; Device: Abbott's FreeStyle Libre; Other: Three-day food journal; Other: Medical visit; Other: Blood pressure measurements; Other: Anthropometric parameters measurements; Other: Indirect calorimetry test; Other: Well-being questionnaire; Other: Diet appreciation questionnaire; Device: Pedometer (PiezoRxD); Other: Hepatic imaging (MRI); Other: Glucagon efficiency test; Other: Body composition : Dual Energy X-ray absorptiometry (DEXA); Other: Blood tests; Other: Stool sample collections (optional); Other: Hypoglycemia journal; Other: Ketone journal; Other: Adherence to the diet (Keenoa) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of time-in-target (range of 4-10 mmol/L)
Using continuous glucose monitoring (FreeStyle Libre)
Measured: From enrollment to end of study, total of 14 weeks
Secondary outcomes (63)
Time to resolve an induced hypoglycemia (>4 mmol/L)
Glucagon efficiency test
Measured: After administration of subcutaneous insulin; At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 5 hours
Peak plasma glucose level two hours after glucagon administration
Glucagon efficiency test
Measured: After administration of glucagon; At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 5 hours
Glycated hemoglobin (HbA1c)
Average glycemic control
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Fructosamine
Average glycemic control
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Fasting blood glucose
Blood glucose before meals
Measured: From beginning (week 3) to end (week 14) of diet intervention
Post-prandial blood glucose
Blood glucose after meals
Measured: From beginning (week 3) to end (week 14) of diet intervention
Coefficient of glucose variation (%)
Using continuous glucose monitoring (FreeStyle Libre)
Measured: From enrollment to end of study, total of 14 weeks
Insulin daily dose
Using continuous glucose monitoring (FreeStyle Libre) or their insulin pump
Measured: From enrollment to end of study, total of 14 weeks
Basal insulin doses
Using continuous glucose monitoring (FreeStyle Libre) or their insulin pump
Measured: From enrollment to end of study, total of 14 weeks
Insulin-to-CHO ratio
Using continuous glucose monitoring (FreeStyle Libre) or their insulin pump
Measured: From enrollment to end of study, total of 14 weeks
Percentage of time spent in hypoglycemia ranges < 4 mmol/L
Using continuous glucose monitoring (FreeStyle Libre)
Measured: From enrollment to end of study, total of 14 weeks
Percentage of time spent in significant hypoglycemia ranges < 3 mmol/L
Using continuous glucose monitoring (FreeStyle Libre)
Measured: From enrollment to end of study, total of 14 weeks
Weight (kg)
Weight and height will be combined to report BMI (kg/m^2)
Measured: At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Height (cm)
Weight and height will be combined to report BMI (kg/m^2)
Measured: At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Waist circumference (cm)
Calculated using the average of 3 measures
Measured: At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Total cholesterol
Blood lipid profiles
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
HDL-cholesterol
Blood lipid profiles
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
LDL-cholesterol
Blood lipid profiles
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Triglycerides
Blood lipid profiles
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Apo-B
Blood lipid profiles
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Apo-A1
Blood lipid profiles
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Total lean mass (kg)
Measured by DEXA (Dual-Energy X-ray Absorptiometry)
Measured: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Total lean mass (%)
Measured by DEXA (Dual-Energy X-ray Absorptiometry)
Measured: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Truncal lean mass (kg)
Measured by DEXA (Dual-Energy X-ray Absorptiometry)
Measured: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Truncal lean mass (%)
Measured by DEXA (Dual-Energy X-ray Absorptiometry)
Measured: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Total fat mass (kg)
Measured by DEXA (Dual-Energy X-ray Absorptiometry)
Measured: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Total fat mass (%)
Measured by DEXA (Dual-Energy X-ray Absorptiometry)
Measured: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Truncal fat mass (kg)
Measured by DEXA (Dual-Energy X-ray Absorptiometry)
Measured: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Truncal fat mass (%)
Measured by DEXA (Dual-Energy X-ray Absorptiometry)
Measured: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Systolic blood pressure (mmHg)
Calculated using the average of 3 measures
Measured: At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Diastolic blood pressure (mmHg)
Calculated using the average of 3 measures
Measured: At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Aminotransferases
Liver function
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Alkaline phosphatase
Liver function
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Gamma-glutamyl transpeptidase
Liver function
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Bilirubin
Liver function
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Albumin
Liver function
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
High sensitivity CRP
Liver function
Measured: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Resting metabolic rate (kcal/day)
Measured by indirect calorimetry
Measured: During indirect calorimetry test : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Respiratory quotient
Measured by indirect calorimetry
Measured: During indirect calorimetry test : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Liver proton density fat fraction
Hepatic fat imagery measured by MRI
Measured: During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Mean liver PDFF
Hepatic fat imagery measured by MRI
Measured: During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Total liver volume
Hepatic fat imagery measured by MRI
Measured: During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Total liver fat index
Hepatic fat imagery measured by MRI
Measured: During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Well-being score
The World Health Organisation- Five Well-Being Index (WHO-5) : I have felt cheerful in good spirits, I have felt calm and relaxed, I have felt active and vigorous, I woke up feeling fresh and rested, My daily life has been filled with things that interest me. The raw score is calculated by totaling the figures of the five answers (0 = At no time to 5 = All of the time). The raw score ranges from 0 to 25, 0 representing worst possible and 25 representing best possible quality of life.
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Visual Analog Score for fatigue (none to intolerable)
Corresponding scores of questionnaire used to assess different quality of life aspects.
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Visual Analog Score for nausea (none to intolerable)
Corresponding scores of questionnaire used to assess different quality of life aspects.
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Visual Analog Score for abdominal cramp/pain (none to intolerable)
Corresponding scores of questionnaire used to assess different quality of life aspects.
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Visual Analog Score for headache (none to intolerable)
Corresponding scores of questionnaire used to assess different quality of life aspects.
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Visual Analog Score for hunger (none to intolerable)
Corresponding scores of questionnaire used to assess different quality of life aspects.
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Visual Analog Score for diet satisfaction (not appreciated to very appreciated)
Corresponding scores of questionnaire for diet appreciation.
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Visual Analog Score for difficulty to follow the diet (no difficulty to extreme difficulty)
Corresponding scores of questionnaire for diet appreciation.
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Visual Analog Score for difficulty for meal preparation (no difficulty to extreme difficulty)
Corresponding scores of questionnaire for diet appreciation.
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Steps/day (physical activity)
Recorded with a pedometer (PiezoRxD) and mobile application
Measured: From enrollment to end of study, total of 14 weeks
Number hypoglycemia episodes
Recorded by participants on hypoglycemia journal
Measured: From enrollment to end of study, total of 14 weeks
Severity of hypoglycemia episodes (mild or severe)
Recorded by participants on hypoglycemia journal
Measured: From enrollment to end of study, total of 14 weeks
Capillary ketone body levels
ß-hydroxybutarate level (mmol/L) measured using ketometer integrated in Abbott's Freestyle-Libre scanner
Measured: From beginning (week 3) to end (week 14) of diet intervention
Alpha diversity (optional)
Intestinal microbiota composition (optional)
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Beta diversity (optional)
Intestinal microbiota composition (optional)
Measured: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Daily caloric intake (kcal/day)
Using Keenoa's mobile application
Measured: Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
Lipids composition
Using Keenoa's mobile application. Grams will be converted into percentage of energy.
Measured: Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
Carbohydrates composition
Using Keenoa's mobile application. Grams will be converted into percentage of energy.
Measured: Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
Proteins composition
Using Keenoa's mobile application. Grams will be converted into percentage of energy.
Measured: Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
Self-reported symptoms
Descriptive symptoms reported by participants during follow-ups
Measured: From enrollment to end of study, total of 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2021
- Study startMar 2021 (estimated)
- Primary completionMar 2023 (estimated)
- Study completionMar 2023 (estimated)
Why it stopped: Not approved by REB
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Recherches Cliniques de Montreal
- Sponsor type
- University, hospital or other
- Collaborators
- McGill University
- Responsible party
- Principal investigator, Rémi Rabasa-Lhoret, Institut de Recherches Cliniques de Montreal
- Investigators
- Rémi Rabasa-Lhoret, Principal investigator, Institut de Recherches Cliniques de Montreal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04758858
- Sponsor's protocol ID
- CUT-1
- Status last verified
- Jul 2021
- First submitted
- 10 Feb 2021
- Last updated
- 13 Jul 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carbohydrates Under Target for Type 1 Diabetes Management
- ClinicalTrials.gov ID
- NCT04758858
- Acronym / sponsor ID
- CUT-1
- Conditions
- Type 1 Diabetes
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Not approved by REB
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Institut de Recherches Cliniques de MontrealUniversity, hospital or other
- Collaborators
- McGill University
- Study start
- Mar 2021 (estimated)
- Primary completion
- Mar 2023 (estimated)
- Study completion
- Mar 2023 (estimated)
- First posted
- 17 Feb 2021 (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.
Recently, there has been an increased interest in limiting carbohydrates (CHO) intakes for improving long-term health. Low CHO (<30% energy from CHO) and very low CHO high fat (VLCHF; 10% CHO, 75% Lipid) diets are being advocated among people living with diabetes given their almost immediate favorable impact on post-prandial blood glucose levels and on hemoglobin A1c that have been reported by users. Adoption of these diets are met with reluctance by healthcare professionals due to the lack of information on their safety. Concerns include the impact on hypoglycemia frequency and glucagon response to hypoglycemia, diabetic ketoacidosis, lipid profile, liver function insulin dose adjustments when adopting them in the context of type 1 diabetes (T1D). Through a series of interviews, people with diabetes following a VLCHF reported that the lack of support from HCPs often leads to hiding the fact that they have adopted a VLCHF diet. This is an important source of concern that can lead to additional safety issues.
The goal is to fill an important knowledge gap about the effectiveness, benefits and risks of low CHO and VLCHF diets for people with T1D. The primary objective is to compare the percentage of TIR of adults with T1D following a low-CHO diet or a VLCHF diet versus a control diet for 12 weeks. The secondary objectives are (1) to evaluate efficacy of glucagon in correcting hypoglycemia in the context of restricted carbohydrates intakes; (2) to evaluate changes in HbA1c at 12 weeks and glucose fluctuations and % of time in hypoglycemia at 6 weeks and 12 weeks of control diet, low-CHO diet or VLCHF diet; (3) to compare key cardiometabolic risk factors (body composition, blood lipids, blood pressure and liver inflammatory markers and function) at 6 weeks and 12 weeks of control diet, low-CHO diet or VLCHF diet; (4) to evaluate the effect of restrictive CHO diets (low-CHO and VLCHF) on the composition of the intestinal microbiota (optional).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| VLCHF (Very Low CHO High Fat) Diet | Active comparator | Other: Insulin treatment optimization with participant's usual diet, Device: Abbott's FreeStyle Libre, Other: Three-day food journal, Other: Medical visit, Other: Blood pressure measurements, Other: Anthropometric parameters measurements, Other: Indirect calorimetry test, Other: Well-being questionnaire, Other: Diet appreciation questionnaire, Device: Pedometer (PiezoRxD), Other: Hepatic imaging (MRI), Other: Glucagon efficiency test, Other: Body composition : Dual Energy X-ray absorptiometry (DEXA), Other: Blood tests, Other: Stool sample collections (optional), Other: Hypoglycemia journal, Other: Ketone journal, Other: Adherence to the diet (Keenoa)10% of energy from CHO, 15% proteins, and 75% lipids |
| Low-CHO Diet | Active comparator | Other: Insulin treatment optimization with participant's usual diet, Device: Abbott's FreeStyle Libre, Other: Three-day food journal, Other: Medical visit, Other: Blood pressure measurements, Other: Anthropometric parameters measurements, Other: Indirect calorimetry test, Other: Well-being questionnaire, Other: Diet appreciation questionnaire, Device: Pedometer (PiezoRxD), Other: Hepatic imaging (MRI), Other: Glucagon efficiency test, Other: Body composition : Dual Energy X-ray absorptiometry (DEXA), Other: Blood tests, Other: Stool sample collections (optional), Other: Hypoglycemia journal, Other: Ketone journal, Other: Adherence to the diet (Keenoa)30% of energy from CHO, 15% proteins and 55% lipids |
| Control Diet | Placebo comparator | Other: Insulin treatment optimization with participant's usual diet, Device: Abbott's FreeStyle Libre, Other: Three-day food journal, Other: Medical visit, Other: Blood pressure measurements, Other: Anthropometric parameters measurements, Other: Indirect calorimetry test, Other: Well-being questionnaire, Other: Diet appreciation questionnaire, Device: Pedometer (PiezoRxD), Other: Hepatic imaging (MRI), Other: Glucagon efficiency test, Other: Body composition : Dual Energy X-ray absorptiometry (DEXA), Other: Blood tests, Other: Stool sample collections (optional), Other: Hypoglycemia journal, Other: Ketone journal, Other: Adherence to the diet (Keenoa)50% of energy from CHO, 15% proteins and 35% lipids |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women > 18 years old
- Duration of T1D > 12 months
- On intensive insulin therapy
- Own a smartphone or tablet to use two mobile applications for nutritional and physical activity tracking: Keenoa and Piezo: Achieve the Guidelines!
Key exclusion criteria (14 listed)
- Already following a low-CHO diet (<30% CHO)
- Type 2 diabetes or other form of diabetes
- Known gastroparesis (clinical diagnosis)
- Advanced kidney disease (eGFR < 50 mL/min)
- Known significant liver disease (e.g. cirrhosis, active hepatitis, liver transplantation)
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 |
|---|---|---|
| Insulin treatment optimization with participant's usual dietTwo weeks before the intervention phase, insulin dose optimization and revision of participants' knowledge on carbohydrates counting, hypo- and hyperglycemia prevention and treatment will be done with a nurse and a dietitian under a physician's supervision. Once to twice a week, participants will be contacted to review if glucose values are in target. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Abbott's FreeStyle LibreDuring the whole trial, blood glucose will be assessed by intermittent scanning Continuous Glucose Monitors (isCGM; Abbott's Freestyle-Libre glucose sensor). Participants will be asked to record or download, in their Freestyle Libre reader or in their insulin pump, their insulin doses being injected each day. | Device | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Three-day food journalTwo weeks before the intervention phase, participants will be asked to complete a 3-day food journal, using the Keenoa mobile application, with carbohydrates (CHO) content of food and blood glucose measures to optimize their insulin doses. Analysis of the food journal will allow us to quantify the participants' usual diet. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Medical visitDuring visit 1, a short medical interview will be done to establish if the subject is eligible to participate in the study. A list of current medications, presence of complications, as well as comorbidities associated with their diabetes will be collected in their medical file during the visit with the endocrinologist. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Blood pressure measurementsBlood pressure (systolic and diastolic blood pressure) will be measured during all visits (visits 1 to 4). | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Anthropometric parameters measurementsWeight, height, BMI and waist circumference will be measured during all visits (visits 1 to 4). | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Indirect calorimetry testBoth resting metabolic rate and respiratory quotient will be measured after a 10-hour fast by indirect calorimetry. The test will be done twice, before (visit 2) and after (visit 4) the intervention phase. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Well-being questionnaireParticipants will be asked to complete a well-being questionnaire (nausea, fatigue, etc) during visits 2, 3 and 4. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Diet appreciation questionnaireParticipants will be asked to complete a diet appreciation (appetite, fullness, etc) questionnaire during visits 3 and 4. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Pedometer (PiezoRxD)Participants will be asked to wear a pedometer (PiezoRxD) that will record their steps every day during the whole trial. Also, they will have to install Piezo: Achieve the Guidelines!, a free mobile application, on their smartphone or tablet. It will connect to their pedometer via bluetooth and will help the research assistant track their data remotely | Device | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Hepatic imaging (MRI)Imaging of participants' liver will be done by MRI at the Centre Hospitalier de l'Université de Montréal (CHUM). The test will be done twice, before (visit 2) and after (visit 4) the intervention phase. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Glucagon efficiency testThe glucagon efficiency test will be done twice, before (visit 2) and after (visit 4) the intervention phase. A subcutaneous insulin injection based on individual insulin correction factor will be given to induce hypoglycemia down to 3 mmol/L (based on plasma glucose). A subcutaneous injection of 300 µg of glucagon will be administered. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Body composition : Dual Energy X-ray absorptiometry (DEXA)Lean body mass and fat mass will be measured by Dual Energy X-ray absorptiometry (DEXA). The DEXA test will be done twice, before (visit 2) and after (visit 4) the intervention phase. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Blood testsBlood tests will be done to assess participants' diabetes control as well as to assess other biochemical markers (blood lipids as well as markers of inflammation and liver function). Blood will be collected and analyzed during all visits (visits 1 to 4). | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Stool sample collections (optional)Participants will be asked to collect and immediately freeze their stool sample until it is given to the study team (for intestinal microbiota composition analysis). This will be done three times during the study, during phase 1, between week 1 and 6 of phase 2 and between week 6 and 12 of phase 2. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Hypoglycemia journalDuring the whole trial, participants will be asked to keep a log of their hypoglycemia episodes, which are defined by the need to consume CHO. They will be asked to note the time, symptoms (including time taken for disappearance after treatment), capillary glucose measurement and the amount of CHO consumed. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Ketone journalDuring the intervention phase, participants will be asked to measure their ß-hydroxybutarate level (mmol/L) with their Abbott's Freestyle-Libre scanner at least twice per week before breakfast. Participants will be asked to check their ketone bodies for sensor or capillary glucose levels exceeding 15 mmol/l, when their sensor indicates high without a specific glucose value and when they have symptoms of ketoacidosis (regardless of glucose reading). | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
| Adherence to the diet (Keenoa)During the whole dietary intervention phase (phase 2), participants will confirm that they have followed their menus by taking before and after pictures of their meals every day and indicating the percentage of their meal consumed (25-50-75-100%) via the Keenoa mobile application. | Other | Control Diet, Low-CHO Diet, VLCHF (Very Low CHO High Fat) Diet |
Primary outcome
Percentage of time-in-target (range of 4-10 mmol/L)
Time frame: From enrollment to end of study, total of 14 weeks
Using continuous glucose monitoring (FreeStyle Libre)
63 secondary outcomes
Time to resolve an induced hypoglycemia (>4 mmol/L)
Time frame: After administration of subcutaneous insulin; At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 5 hours
Peak plasma glucose level two hours after glucagon administration
Time frame: After administration of glucagon; At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 5 hours
Glycated hemoglobin (HbA1c)
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Fructosamine
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Fasting blood glucose
Time frame: From beginning (week 3) to end (week 14) of diet intervention
Post-prandial blood glucose
Time frame: From beginning (week 3) to end (week 14) of diet intervention
Coefficient of glucose variation (%)
Time frame: From enrollment to end of study, total of 14 weeks
Insulin daily dose
Time frame: From enrollment to end of study, total of 14 weeks
Basal insulin doses
Time frame: From enrollment to end of study, total of 14 weeks
Insulin-to-CHO ratio
Time frame: From enrollment to end of study, total of 14 weeks
Percentage of time spent in hypoglycemia ranges < 4 mmol/L
Time frame: From enrollment to end of study, total of 14 weeks
Percentage of time spent in significant hypoglycemia ranges < 3 mmol/L
Time frame: From enrollment to end of study, total of 14 weeks
Weight (kg)
Time frame: At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Height (cm)
Time frame: At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Waist circumference (cm)
Time frame: At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Total cholesterol
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
HDL-cholesterol
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
LDL-cholesterol
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Triglycerides
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Apo-B
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Apo-A1
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Total lean mass (kg)
Time frame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Total lean mass (%)
Time frame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Truncal lean mass (kg)
Time frame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Truncal lean mass (%)
Time frame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Total fat mass (kg)
Time frame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Total fat mass (%)
Time frame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Truncal fat mass (kg)
Time frame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Truncal fat mass (%)
Time frame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Systolic blood pressure (mmHg)
Time frame: At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Diastolic blood pressure (mmHg)
Time frame: At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Aminotransferases
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Alkaline phosphatase
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Gamma-glutamyl transpeptidase
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Bilirubin
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Albumin
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
High sensitivity CRP
Time frame: During blood test : At baseline (day 1), before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Resting metabolic rate (kcal/day)
Time frame: During indirect calorimetry test : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Respiratory quotient
Time frame: During indirect calorimetry test : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Liver proton density fat fraction
Time frame: During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
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 13 Jul 2021.
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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.
Rémi Rabasa-Lhoret principal investigator
Institut de Recherches Cliniques de Montreal
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Insulin treatment optimization with participant's usual diet, Abbott's FreeStyle Libre and Three-day food journal in people with Type 1 Diabetes, run by Institut de Recherches Cliniques de Montreal at 1 site in Canada.
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 4 inclusion and 14 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 13 Jul 2021. 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 Canada. 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. Some participants in this study may receive a placebo. 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 (range of 4-10 mmol/L) (time frame: From enrollment to end of study, total of 14 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 13 Jul 2021.