Clinical trial NCT04758858: Carbohydrates Under Target for Type 1 Diabetes Management
Official title: Carbohydrates Under Target for Type 1 Diabetes Management
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Type 1 Diabetes
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
Collaborators: name: McGill University
First posted: 2021-02-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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®)

Primary outcomes:
measure: Percentage of time-in-target (range of 4-10 mmol/L)
timeFrame: From enrollment to end of study, total of 14 weeks
Secondary outcomes:
measure: Time to resolve an induced hypoglycemia (>4 mmol/L)
timeFrame: After administration of subcutaneous insulin; At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 5 hours
measure: Peak plasma glucose level two hours after glucagon administration
timeFrame: After administration of glucagon; At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 5 hours
measure: Glycated hemoglobin (HbA1c)
timeFrame: 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)
measure: Fructosamine
timeFrame: 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)
measure: Fasting blood glucose
timeFrame: From beginning (week 3) to end (week 14) of diet intervention
measure: Post-prandial blood glucose
timeFrame: From beginning (week 3) to end (week 14) of diet intervention
measure: Coefficient of glucose variation (%)
timeFrame: From enrollment to end of study, total of 14 weeks
measure: Insulin daily dose
timeFrame: From enrollment to end of study, total of 14 weeks
measure: Basal insulin doses
timeFrame: From enrollment to end of study, total of 14 weeks
measure: Insulin-to-CHO ratio
timeFrame: From enrollment to end of study, total of 14 weeks
measure: Percentage of time spent in hypoglycemia ranges < 4 mmol/L
timeFrame: From enrollment to end of study, total of 14 weeks
measure: Percentage of time spent in significant hypoglycemia ranges < 3 mmol/L
timeFrame: From enrollment to end of study, total of 14 weeks
measure: Weight (kg)
timeFrame: 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)
measure: Height (cm)
timeFrame: 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)
measure: Waist circumference (cm)
timeFrame: 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)
measure: Total cholesterol
timeFrame: 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)
measure: HDL-cholesterol
timeFrame: 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)
measure: LDL-cholesterol
timeFrame: 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)
measure: Triglycerides
timeFrame: 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)
measure: Apo-B
timeFrame: 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)
measure: Apo-A1
timeFrame: 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)
measure: Total lean mass (kg)
timeFrame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
measure: Total lean mass (%)
timeFrame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
measure: Truncal lean mass (kg)
timeFrame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
measure: Truncal lean mass (%)
timeFrame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
measure: Total fat mass (kg)
timeFrame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
measure: Total fat mass (%)
timeFrame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
measure: Truncal fat mass (kg)
timeFrame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
measure: Truncal fat mass (%)
timeFrame: During DEXA-scan : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 15 minutes
measure: Systolic blood pressure (mmHg)
timeFrame: 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)
measure: Diastolic blood pressure (mmHg)
timeFrame: 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)
measure: Aminotransferases
timeFrame: 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)
measure: Alkaline phosphatase
timeFrame: 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)
measure: Gamma-glutamyl transpeptidase
timeFrame: 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)
measure: Bilirubin
timeFrame: 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)
measure: Albumin
timeFrame: 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)
measure: High sensitivity CRP
timeFrame: 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)
measure: Resting metabolic rate (kcal/day)
timeFrame: During indirect calorimetry test : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
measure: Respiratory quotient
timeFrame: During indirect calorimetry test : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
measure: Liver proton density fat fraction
timeFrame: During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
measure: Mean liver PDFF
timeFrame: During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
measure: Total liver volume
timeFrame: During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
measure: Total liver fat index
timeFrame: During MRI : At beginning (week 3) and end (week 14) of the diet intervention, each test lasts approximately 30 minutes
measure: Well-being score
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Visual Analog Score for fatigue (none to intolerable)
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Visual Analog Score for nausea (none to intolerable)
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Visual Analog Score for abdominal cramp/pain (none to intolerable)
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Visual Analog Score for headache (none to intolerable)
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Visual Analog Score for hunger (none to intolerable)
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Visual Analog Score for diet satisfaction (not appreciated to very appreciated)
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Visual Analog Score for difficulty to follow the diet (no difficulty to extreme difficulty)
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Visual Analog Score for difficulty for meal preparation (no difficulty to extreme difficulty)
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Steps/day (physical activity)
timeFrame: From enrollment to end of study, total of 14 weeks
measure: Number hypoglycemia episodes
timeFrame: From enrollment to end of study, total of 14 weeks
measure: Severity of hypoglycemia episodes (mild or severe)
timeFrame: From enrollment to end of study, total of 14 weeks
measure: Capillary ketone body levels
timeFrame: From beginning (week 3) to end (week 14) of diet intervention
measure: Alpha diversity (optional)
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Beta diversity (optional)
timeFrame: Before diet intervention (week 3), halfway the diet intervention (week 8) and at the end of the diet intervention (week 14)
measure: Daily caloric intake (kcal/day)
timeFrame: Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
measure: Lipids composition
timeFrame: Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
measure: Carbohydrates composition
timeFrame: Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
measure: Proteins composition
timeFrame: Three days during the first 2 weeks (3-day food journal) and from beginning (week 3) to end (week 14) of diet intervention
measure: Self-reported symptoms
timeFrame: From enrollment to end of study, total of 14 weeks
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Institut de recherches cliniques de Montréal
state: Quebec
Study officials:
affiliation: Institut de recherches cliniques de Montréal
name: Rémi Rabasa-Lhoret
role: PRINCIPAL_INVESTIGATOR
References: