Carbohydrates Under Target for Type 1 Diabetes Management

Not Applicable

Withdrawn

• Conditions: Type 1 Diabetes
• Interventions: 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: Blood tests; Other: Stool sample collections (optional); Other: Hypoglycemia journal; Other: Ketone journal; Other: Adherence to the diet (Keenoa)

• Registration Number: NCT04758858
• Lead Sponsor: Institut de Recherches Cliniques de Montreal

Brief 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-10
• Study First Submitted QC: 2021-02-15
• Study First Posted: 2021-02-17
• Study Start: 2021-03
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-07
• Last Update Posted: 2021-07-13
• Primary Completion: 2023-03
• Study Completion: 2023-03

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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®)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VLCHF (Very Low CHO High Fat) Diet	Insulin treatment optimization with participant's usual diet	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Three-day food journal	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Medical visit	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Blood pressure measurements	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Anthropometric parameters measurements	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Diet appreciation questionnaire	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Hepatic imaging (MRI)	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Glucagon efficiency test	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Blood tests	10% of energy from CHO, 15% proteins, and 75% lipids
Low-CHO Diet	Blood pressure measurements	30% of energy from CHO, 15% proteins and 55% lipids
VLCHF (Very Low CHO High Fat) Diet	Abbott's FreeStyle Libre	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Indirect calorimetry test	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Stool sample collections (optional)	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Adherence to the diet (Keenoa)	10% of energy from CHO, 15% proteins, and 75% lipids
Control Diet	Glucagon efficiency test	50% of energy from CHO, 15% proteins and 35% lipids
Low-CHO Diet	Diet appreciation questionnaire	30% of energy from CHO, 15% proteins and 55% lipids
Control Diet	Three-day food journal	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Medical visit	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Anthropometric parameters measurements	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Ketone journal	50% of energy from CHO, 15% proteins and 35% lipids
VLCHF (Very Low CHO High Fat) Diet	Well-being questionnaire	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Ketone journal	10% of energy from CHO, 15% proteins, and 75% lipids
Low-CHO Diet	Three-day food journal	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Anthropometric parameters measurements	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Glucagon efficiency test	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Ketone journal	30% of energy from CHO, 15% proteins and 55% lipids
Control Diet	Insulin treatment optimization with participant's usual diet	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Blood pressure measurements	50% of energy from CHO, 15% proteins and 35% lipids
VLCHF (Very Low CHO High Fat) Diet	Pedometer (PiezoRxD)	10% of energy from CHO, 15% proteins, and 75% lipids
VLCHF (Very Low CHO High Fat) Diet	Hypoglycemia journal	10% of energy from CHO, 15% proteins, and 75% lipids
Low-CHO Diet	Insulin treatment optimization with participant's usual diet	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Abbott's FreeStyle Libre	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Indirect calorimetry test	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Well-being questionnaire	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Pedometer (PiezoRxD)	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Hepatic imaging (MRI)	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Medical visit	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Blood tests	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Hypoglycemia journal	30% of energy from CHO, 15% proteins and 55% lipids
Control Diet	Indirect calorimetry test	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Well-being questionnaire	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Pedometer (PiezoRxD)	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Hepatic imaging (MRI)	50% of energy from CHO, 15% proteins and 35% lipids
Low-CHO Diet	Stool sample collections (optional)	30% of energy from CHO, 15% proteins and 55% lipids
Low-CHO Diet	Adherence to the diet (Keenoa)	30% of energy from CHO, 15% proteins and 55% lipids
Control Diet	Abbott's FreeStyle Libre	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Diet appreciation questionnaire	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Blood tests	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Hypoglycemia journal	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Stool sample collections (optional)	50% of energy from CHO, 15% proteins and 35% lipids
Control Diet	Adherence to the diet (Keenoa)	50% of energy from CHO, 15% proteins and 35% lipids

Primary Outcome Measures

Name	Time	Method
Percentage of time-in-target (range of 4-10 mmol/L)	From enrollment to end of study, total of 14 weeks	Using continuous glucose monitoring (FreeStyle Libre)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Institut de recherches cliniques de Montréal; 🇨🇦 Montréal, Quebec, Canada