Carbohydrates Under Target for Type 1 Diabetes Management

Type 1 Diabetes Clinical Trial

Official title:

Carbohydrates Under Target for Type 1 Diabetes Management

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04758858
• Other study ID #: CUT-1
• Status: Withdrawn
• Phase: N/A
• Start date: March 2021
• Est. completion date: March 2023

Study information

• Verified date: July 2021
• Source: Institut de Recherches Cliniques de Montreal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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!

Exclusion Criteria:

• 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.)

• 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®)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Other:
• Insulin treatment optimization with participant's usual diet
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.

Device:
• Abbott's FreeStyle Libre
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.

Other:
• Three-day food journal
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 visit
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 measurements
Blood pressure (systolic and diastolic blood pressure) will be measured during all visits (visits 1 to 4).
• Anthropometric parameters measurements
Weight, height, BMI and waist circumference will be measured during all visits (visits 1 to 4).
• Indirect calorimetry test
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 questionnaire
Participants will be asked to complete a well-being questionnaire (nausea, fatigue, etc) during visits 2, 3 and 4.
• Diet appreciation questionnaire
Participants will be asked to complete a diet appreciation (appetite, fullness, etc) questionnaire during visits 3 and 4.

Device:
• 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

Other:
• 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.
• Glucagon efficiency test
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)
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 tests
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)
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 journal
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 journal
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)
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.

Locations

Country	Name	City	State
Canada	Institut de recherches cliniques de Montréal	Montréal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Cliniques de Montreal	McGill University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of time-in-target (range of 4-10 mmol/L)	Using continuous glucose monitoring (FreeStyle Libre)	From enrollment to end of study, total of 14 weeks
Secondary	Time to resolve an induced hypoglycemia (>4 mmol/L)	Glucagon efficiency test	After administration of subcutaneous insulin; At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 5 hours
Secondary	Peak plasma glucose level two hours after glucagon administration	Glucagon efficiency test	After administration of glucagon; At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 5 hours
Secondary	Glycated hemoglobin (HbA1c)	Average glycemic control	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)
Secondary	Fructosamine	Average glycemic control	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)
Secondary	Fasting blood glucose	Blood glucose before meals	From beginning (week 3) to end (week 14) of diet intervention
Secondary	Post-prandial blood glucose	Blood glucose after meals	From beginning (week 3) to end (week 14) of diet intervention
Secondary	Coefficient of glucose variation (%)	Using continuous glucose monitoring (FreeStyle Libre)	From enrollment to end of study, total of 14 weeks
Secondary	Insulin daily dose	Using continuous glucose monitoring (FreeStyle Libre) or their insulin pump	From enrollment to end of study, total of 14 weeks
Secondary	Basal insulin doses	Using continuous glucose monitoring (FreeStyle Libre) or their insulin pump	From enrollment to end of study, total of 14 weeks
Secondary	Insulin-to-CHO ratio	Using continuous glucose monitoring (FreeStyle Libre) or their insulin pump	From enrollment to end of study, total of 14 weeks
Secondary	Percentage of time spent in hypoglycemia ranges < 4 mmol/L	Using continuous glucose monitoring (FreeStyle Libre)	From enrollment to end of study, total of 14 weeks
Secondary	Percentage of time spent in significant hypoglycemia ranges < 3 mmol/L	Using continuous glucose monitoring (FreeStyle Libre)	From enrollment to end of study, total of 14 weeks
Secondary	Weight (kg)	Weight and height will be combined to report BMI (kg/m^2)	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)
Secondary	Height (cm)	Weight and height will be combined to report BMI (kg/m^2)	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)
Secondary	Waist circumference (cm)	Calculated using the average of 3 measures	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)
Secondary	Total cholesterol	Blood lipid profiles	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)
Secondary	HDL-cholesterol	Blood lipid profiles	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)
Secondary	LDL-cholesterol	Blood lipid profiles	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)
Secondary	Triglycerides	Blood lipid profiles	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)
Secondary	Apo-B	Blood lipid profiles	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)
Secondary	Apo-A1	Blood lipid profiles	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)
Secondary	Total lean mass (kg)	Measured by DEXA (Dual-Energy X-ray Absorptiometry)	During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Secondary	Total lean mass (%)	Measured by DEXA (Dual-Energy X-ray Absorptiometry)	During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Secondary	Truncal lean mass (kg)	Measured by DEXA (Dual-Energy X-ray Absorptiometry)	During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Secondary	Truncal lean mass (%)	Measured by DEXA (Dual-Energy X-ray Absorptiometry)	During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Secondary	Total fat mass (kg)	Measured by DEXA (Dual-Energy X-ray Absorptiometry)	During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Secondary	Total fat mass (%)	Measured by DEXA (Dual-Energy X-ray Absorptiometry)	During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Secondary	Truncal fat mass (kg)	Measured by DEXA (Dual-Energy X-ray Absorptiometry)	During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Secondary	Truncal fat mass (%)	Measured by DEXA (Dual-Energy X-ray Absorptiometry)	During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
Secondary	Systolic blood pressure (mmHg)	Calculated using the average of 3 measures	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)
Secondary	Diastolic blood pressure (mmHg)	Calculated using the average of 3 measures	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)
Secondary	Aminotransferases	Liver function	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)
Secondary	Alkaline phosphatase	Liver function	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)
Secondary	Gamma-glutamyl transpeptidase	Liver function	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)
Secondary	Bilirubin	Liver function	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)
Secondary	Albumin	Liver function	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)
Secondary	High sensitivity CRP	Liver function	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)
Secondary	Resting metabolic rate (kcal/day)	Measured by indirect calorimetry	During indirect calorimetry test : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Secondary	Respiratory quotient	Measured by indirect calorimetry	During indirect calorimetry test : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Secondary	Liver proton density fat fraction	Hepatic fat imagery measured by MRI	During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Secondary	Mean liver PDFF	Hepatic fat imagery measured by MRI	During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Secondary	Total liver volume	Hepatic fat imagery measured by MRI	During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Secondary	Total liver fat index	Hepatic fat imagery measured by MRI	During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
Secondary	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.	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Visual Analog Score for fatigue (none to intolerable)	Corresponding scores of questionnaire used to assess different quality of life aspects.	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Visual Analog Score for nausea (none to intolerable)	Corresponding scores of questionnaire used to assess different quality of life aspects.	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Visual Analog Score for abdominal cramp/pain (none to intolerable)	Corresponding scores of questionnaire used to assess different quality of life aspects.	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Visual Analog Score for headache (none to intolerable)	Corresponding scores of questionnaire used to assess different quality of life aspects.	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Visual Analog Score for hunger (none to intolerable)	Corresponding scores of questionnaire used to assess different quality of life aspects.	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Visual Analog Score for diet satisfaction (not appreciated to very appreciated)	Corresponding scores of questionnaire for diet appreciation.	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Visual Analog Score for difficulty to follow the diet (no difficulty to extreme difficulty)	Corresponding scores of questionnaire for diet appreciation.	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Visual Analog Score for difficulty for meal preparation (no difficulty to extreme difficulty)	Corresponding scores of questionnaire for diet appreciation.	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Steps/day (physical activity)	Recorded with a pedometer (PiezoRxD) and mobile application	From enrollment to end of study, total of 14 weeks
Secondary	Number hypoglycemia episodes	Recorded by participants on hypoglycemia journal	From enrollment to end of study, total of 14 weeks
Secondary	Severity of hypoglycemia episodes (mild or severe)	Recorded by participants on hypoglycemia journal	From enrollment to end of study, total of 14 weeks
Secondary	Capillary ketone body levels	ß-hydroxybutarate level (mmol/L) measured using ketometer integrated in Abbott's Freestyle-Libre scanner	From beginning (week 3) to end (week 14) of diet intervention
Secondary	Alpha diversity (optional)	Intestinal microbiota composition (optional)	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Beta diversity (optional)	Intestinal microbiota composition (optional)	Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
Secondary	Daily caloric intake (kcal/day)	Using Keenoa's mobile application	Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
Secondary	Lipids composition	Using Keenoa's mobile application. Grams will be converted into percentage of energy.	Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
Secondary	Carbohydrates composition	Using Keenoa's mobile application. Grams will be converted into percentage of energy.	Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
Secondary	Proteins composition	Using Keenoa's mobile application. Grams will be converted into percentage of energy.	Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
Secondary	Self-reported symptoms	Descriptive symptoms reported by participants during follow-ups	From enrollment to end of study, total of 14 weeks