Carbohydrates Under Target for Type 1 Diabetes Management

NCT ID: NCT04758858

Last Updated: 2021-07-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-31

Study Completion Date

2023-03-31

Brief Summary

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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

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Conditions

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Type 1 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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VLCHF (Very Low CHO High Fat) Diet

10% of energy from CHO, 15% proteins, and 75% lipids

Group Type ACTIVE_COMPARATOR

Insulin treatment optimization with participant's usual diet

Intervention Type OTHER

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 Libre

Intervention Type DEVICE

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 journal

Intervention Type OTHER

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

Intervention Type OTHER

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

Intervention Type OTHER

Blood pressure (systolic and diastolic blood pressure) will be measured during all visits (visits 1 to 4).

Anthropometric parameters measurements

Intervention Type OTHER

Weight, height, BMI and waist circumference will be measured during all visits (visits 1 to 4).

Indirect calorimetry test

Intervention Type OTHER

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

Intervention Type OTHER

Participants will be asked to complete a well-being questionnaire (nausea, fatigue, etc) during visits 2, 3 and 4.

Diet appreciation questionnaire

Intervention Type OTHER

Participants will be asked to complete a diet appreciation (appetite, fullness, etc) questionnaire during visits 3 and 4.

Pedometer (PiezoRxD)

Intervention Type 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)

Intervention Type 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 test

Intervention Type OTHER

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)

Intervention Type 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 tests

Intervention Type OTHER

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)

Intervention Type 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 journal

Intervention Type OTHER

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

Intervention Type OTHER

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)

Intervention Type 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.

Low-CHO Diet

30% of energy from CHO, 15% proteins and 55% lipids

Group Type ACTIVE_COMPARATOR

Insulin treatment optimization with participant's usual diet

Intervention Type OTHER

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 Libre

Intervention Type DEVICE

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 journal

Intervention Type OTHER

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

Intervention Type OTHER

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

Intervention Type OTHER

Blood pressure (systolic and diastolic blood pressure) will be measured during all visits (visits 1 to 4).

Anthropometric parameters measurements

Intervention Type OTHER

Weight, height, BMI and waist circumference will be measured during all visits (visits 1 to 4).

Indirect calorimetry test

Intervention Type OTHER

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

Intervention Type OTHER

Participants will be asked to complete a well-being questionnaire (nausea, fatigue, etc) during visits 2, 3 and 4.

Diet appreciation questionnaire

Intervention Type OTHER

Participants will be asked to complete a diet appreciation (appetite, fullness, etc) questionnaire during visits 3 and 4.

Pedometer (PiezoRxD)

Intervention Type 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)

Intervention Type 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 test

Intervention Type OTHER

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)

Intervention Type 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 tests

Intervention Type OTHER

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)

Intervention Type 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 journal

Intervention Type OTHER

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

Intervention Type OTHER

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)

Intervention Type 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.

Control Diet

50% of energy from CHO, 15% proteins and 35% lipids

Group Type PLACEBO_COMPARATOR

Insulin treatment optimization with participant's usual diet

Intervention Type OTHER

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 Libre

Intervention Type DEVICE

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 journal

Intervention Type OTHER

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

Intervention Type OTHER

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

Intervention Type OTHER

Blood pressure (systolic and diastolic blood pressure) will be measured during all visits (visits 1 to 4).

Anthropometric parameters measurements

Intervention Type OTHER

Weight, height, BMI and waist circumference will be measured during all visits (visits 1 to 4).

Indirect calorimetry test

Intervention Type OTHER

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

Intervention Type OTHER

Participants will be asked to complete a well-being questionnaire (nausea, fatigue, etc) during visits 2, 3 and 4.

Diet appreciation questionnaire

Intervention Type OTHER

Participants will be asked to complete a diet appreciation (appetite, fullness, etc) questionnaire during visits 3 and 4.

Pedometer (PiezoRxD)

Intervention Type 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)

Intervention Type 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 test

Intervention Type OTHER

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)

Intervention Type 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 tests

Intervention Type OTHER

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)

Intervention Type 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 journal

Intervention Type OTHER

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

Intervention Type OTHER

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)

Intervention Type 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.

Interventions

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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.

Intervention Type OTHER

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.

Intervention Type DEVICE

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.

Intervention Type OTHER

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.

Intervention Type OTHER

Blood pressure measurements

Blood pressure (systolic and diastolic blood pressure) will be measured during all visits (visits 1 to 4).

Intervention Type OTHER

Anthropometric parameters measurements

Weight, height, BMI and waist circumference will be measured during all visits (visits 1 to 4).

Intervention Type OTHER

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.

Intervention Type OTHER

Well-being questionnaire

Participants will be asked to complete a well-being questionnaire (nausea, fatigue, etc) during visits 2, 3 and 4.

Intervention Type OTHER

Diet appreciation questionnaire

Participants will be asked to complete a diet appreciation (appetite, fullness, etc) questionnaire during visits 3 and 4.

Intervention Type OTHER

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

Intervention Type DEVICE

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.

Intervention Type OTHER

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.

Intervention Type OTHER

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.

Intervention Type OTHER

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).

Intervention Type OTHER

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.

Intervention Type OTHER

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.

Intervention Type OTHER

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).

Intervention Type OTHER

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.

Intervention Type OTHER

Eligibility Criteria

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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®)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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McGill University

OTHER

Sponsor Role collaborator

Institut de Recherches Cliniques de Montreal

OTHER

Sponsor Role lead

Responsible Party

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Rémi Rabasa-Lhoret

Full professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rémi Rabasa-Lhoret

Role: PRINCIPAL_INVESTIGATOR

Institut de recherches cliniques de Montréal

Locations

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Institut de recherches cliniques de Montréal

Montreal, Quebec, Canada

Site Status

Countries

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Canada

Other Identifiers

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CUT-1

Identifier Type: -

Identifier Source: org_study_id

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