Clinical trial NCT03847701: Cardio-metabolic and Inflammatory Impact of Starch Digestibility in Type 2 Diabetic Patients
Official title: Cardio-metabolic and Inflammatory Impact of Starch Digestibility in Type 2 Diabetic Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Type2 Diabetes
Keywords: Slowly Digestible Starch
SDS
Type 2 diabetes
T2D
Glycemic response
Continuous Glucose Monitoring System
CGMS
Diet
MAGE
Mean Amplitude of Glucose Excursion
Lead sponsor: Mondelēz International, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Centre de Recherche en Nutrition Humaine Rhone-Alpe
name: Biofortis Mérieux NutriSciences
First posted: 2019-02-20
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Each participant will be allocated to an intervention arm in a parallel design for 3 months of intervention
Primary purpose: PREVENTION

Brief summary: This is a monocentric, randomized, single-blind and controlled study with a parallel design (2 arms). The research hypothesis is that the diet high in Slow Digestible Starch (SDS) content (H-SDS) will lower the daylong glycemic response and improve the glycemic control just as metabolic, inflammatory, cardiovascular and oxidative stress parameters in patients with type 2 diabetes (T2D) compared to the diet low in SDS content (L-SDS). The hypothesis is that these differences in glycemic response and in metabolic, inflammatory, cardiovascular and oxidative stress parameters response can be observed after 3 months of diet.

Detailed description: This is a monocentric, randomized, single-blind and controlled study with a parallel design (2 arms). The research hypothesis is that the diet high in Slow Digestible Starch (SDS) content (H-SDS) will lower the daylong glycemic response and improve the glycemic control just as metabolic, inflammatory, cardiovascular and oxidative stress parameters in patients with type 2 diabetes (T2D) compared to the diet low in SDS content (L-SDS). The hypothesis is that these differences in glycemic response and in metabolic, inflammatory, cardiovascular and oxidative stress parameters response can be observed after 3 months of diet.

80 patients with type 2 diabetes will be recruited.

Subjects will have 11 visits:

V0 = selection visit: check whether the patients fulfill inclusion and exclusion criteria for the study.

Visit V1 = CGMS insertion on usual lifestyle without any changes in his/her diet. This is the Run-in period.

Visit V2 (6 days +/- 1 day) = CGMS removal and randomization according to sex, HbA1c and MAGE.

Visit V3 = first metabolic day: medical check-up, dietary interview, indirect calorimetry, impedancemetry measurements and FlexMeal challenge test with 5h follow up (blood samples). CGMS insertion with detailed dietetic instructions according to their allocated group (adapted food provisions).

Visit V4 (6 days +/- 1 day) = CGMS removal. Arterial Endothelial Function (AEF) measurement. Adapted food provisions.

Visit V5 = Adapted food provisions.

Visit V6 = medical check-up, dietary interview, CGMS insertion and baseline blood measurements. Adapted food provisions.

Visit V7 (6 days +/- 1 day) = CGMS removal. Arterial Endothelial Function (AEF) measurement. Adapted food provisions.

Visit V8 = Adapted food provisions.

Visit V9 = CGMS insertion. Arterial Endothelial Function (AEF) measurement. Adapted food provisions.

Visit V10 (6 days +/- 1 day) = second metabolic day: medical check-up, dietary interview, indirect calorimetry, impedancemetry measurements and FlexMeal challenge test with 5h follow up (blood samples). CGMS removal. Feedback questionnaire.

Eligibility criteria: Inclusion Criteria:

* Patient able to understand the study information and providing written consent for his/her participation to the study
* Male or female
* Patient undergoing medical examination during the selection visit
* Patient aged between 18 and 75 years old (bounds included)
* T2D volunteer with HbA1c between 7% and 8,5% without signs of insulinopenia according to the investigator
* Patient with BMI ranging between 25 and 40 kg/m2 (bounds included)
* Patient with stable body weight over the past three months (+/- 5 % of body weight)
* Patient accepting to change its diet for three months
* Patient not suffering from food intolerance or allergy
* Patient regularly consuming products proposed in the study
* Patient agreeing to consume 3 main meals per day without extra-prandial carbohydrates intakes
* Sedentary behavior or stable predicted physical activity during the study
* Patient not presenting any disease during the medical examination / interview which could interfere with the results of the study according to the investigator
* Patient covered by health insurance
* Patient accepting to have short nails on his/her 2 forefingers

Exclusion Criteria:

* Patient under legal protection measure
* Patient deprived of liberty by a court or an administrative decision
* Patient currently participating in another study or being in the exclusion period of another study
* Volunteer that exceed the financial compensation allowed per year for participating in research programs
* Gamma-GT \> 2.5 times above the norm (\>160 UI/L)
* ASAT \> 2.5 times above the norm (\>85 UI/L)
* ALAT \> 2.5 times above the norm (\>137.5 UI/L)
* Triglycerides \> 4 g/L
* LDL-cholesterol \> 1.90 g/L
* CRP \> 15 mg/L
* Hemoglobin \< 120 mg/dL
* eGRF (estimated glomerular filtration rate) \< 45 ml/min
* Other biological abnormality with clinical significant relevance according to the investigator
* Patient with type 1 diabetes, post pancreatectomy or post transplant diabetes, MODY diabetes, mitochondrial diabetes, iatrogenic diabetes
* T2D volunteer with any other anti-diabetic treatment other than metformin: insulin therapy, GLP-1 analogues, acarbose, sulphonylureas, repaglinide, SGLT2 agonists,...
* Patient consuming in the two previous months regularly corticoids, beta-blocking drugs or immunosuppressing drugs
* Patient with hemoglobin pathology
* Patient with medical history of hemoglobinopathies (thalassemia, drepanocytosis...)
* Patient with past bariatric surgery
* Patient with medical history of endocrine diseases who may interfere with glucose metabolism according to the investigator (such as hyperthyroidism, acromegaly, hypercorticism...)
* Patient treated with anticoagulants
* Patient with a pace-maker
* Uncontrolled high blood pressure defined by Systolic blood pressure \> 150 mmHg or Diastolic blood pressure \> 100 mmHg
* Evidence of any other unstable or untreated clinically significant immunological, neoplasic, endocrine, haematological, gastrointestinal, hepatic, neurological or psychiatric abnormalities or medical disease with clinical significant relevance according to the investigator
* Pregnant women or willing to become pregnant or lactating women
* Women of childbearing age without an efficient contraceptive method according to the investigator
* Patient under a restrictive diet or with a planned weight loss program during the study
* Patient with severe eating disorders (e.g. anorexia nervosa, binge eating disorder and bulimia) according to the investigator
* Patient without stable dietary habits or with specific diet (vegetarian, vegan, gluten-free...) according to the investigator
* Patient who smokes more than 5 cigarettes per day
* Patient regularly consuming more than 20 g/day of alcohol. Consumption of more than 3 alcoholic beverages per day is recognized as excessive. An alcoholic beverage is: 30 mL of spirituous, 120 mL of wine or 330 mL of beer
* Patient regularly consuming recreational drugs
* Adhesive plaster skin allergy
* Claustrophobic patient
* Patient willing to take the plane during the CGMS periods

Primary outcomes:
measure: MAGE comparison following 3 months of intake of a diet either high or low in SDS
timeFrame: Minimum 3 days to a maximum of 6 days of CGMS record
Secondary outcomes:
measure: Glycemia iAUC characterisation of a standard challenge test (FlexMeal) during the first metabolic day
timeFrame: 5 hours post standard challenge test during visit 3
measure: Insulin iAUC characterisation of a standard challenge test (FlexMeal) during the first metabolic day
timeFrame: 5 hours post standard challenge test during visit 3
measure: GLP1 iAUC characterisation of a standard challenge test (FlexMeal) during the first metabolic day
timeFrame: 5 hours post standard challenge test during visit 3
measure: Inflammatory status comparison during the first metabolic day : CRPus concentration
timeFrame: At a basal state during visit 3
measure: Inflammatory impacts characterisation of a standard challenge test (FlexMeal) during the first metabolic day : TNFa iAUC
timeFrame: 5 hours post standard challenge test during visit 3
measure: Inflammatory impacts characterisation of a standard challenge test (FlexMeal) during the first metabolic day : IL6 iAUC
timeFrame: 5 hours post standard challenge test during visit 3
measure: Inflammatory impacts characterisation of a standard challenge test (FlexMeal) during the first metabolic day : IL1Ra iAUC
timeFrame: 5 hours post standard challenge test during visit 3
measure: Inflammatory impacts characterisation of a standard challenge test (FlexMeal) during the first metabolic day : IL18 iAUC
timeFrame: 5 hours post standard challenge test during visit 3
measure: Glycemic impacts comparison following the intake of a diet either high or low in SDS during the time course of the study
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Insulinemic impacts comparison following the intake of a diet either high or low in SDS during the time course of the study
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Inflammatory impacts comparison following the intake of a diet either high or low in SDS during the time course of the study : CRPus concentration
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Inflammatory impacts comparison following the intake of a diet either high or low in SDS during the time course of the study : TNFa concentration
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Inflammatory impacts comparison following the intake of a diet either high or low in SDS during the time course of the study : IL6 concentration
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Inflammatory impacts comparison following the intake of a diet either high or low in SDS during the time course of the study : IL1Ra concentration
timeFrame: At a basal state during visit V3, V6 and V10
measure: Inflammatory impacts comparison following the intake of a diet either high or low in SDS during the time course of the study : IL18 concentration
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Oxidative Stress comparison following the intake of a diet either high or low in SDS during the time course of the study : MDA concentration
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Oxidative Stress comparison following the intake of a diet either high or low in SDS during the time course of the study : Urinary isoprostanes concentration
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Cardiovascular risk markers comparison following the intake of a diet either high or low in SDS during the time course of the study : MCP1 concentration
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Cardiovascular risk markers comparison following the intake of a diet either high or low in SDS during the time course of the study : sICAM concentration
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Cardiovascular risk markers comparison following the intake of a diet either high or low in SDS during the time course of the study : sVCAM concentration
timeFrame: At a basal state during visit 3, visit 6 and visit 10
measure: Glycemic impacts characterisation of a standard challenge test (FlexMeal) during the second metabolic day
timeFrame: 5 hours post standard challenge test during visit 10
measure: Insulinemic impacts characterisation of a standard challenge test (FlexMeal) during the second metabolic day
timeFrame: 5 hours post standard challenge test during visit 10
measure: GLP1 iAUC characterisation of a standard challenge test (FlexMeal) during the second metabolic day
timeFrame: 5 hours post standard challenge test during visit 10
measure: Inflammatory impacts comparison following 3 months of intake of a diet either high or low in SDS : CRPus concentration
timeFrame: At a basal state during visit 10
measure: Inflammatory impacts characterisation of a standard challenge test (FlexMeal) during the second metabolic day : TNFa iAUC
timeFrame: 5 hours post standard challenge test during visit 10
measure: Inflammatory impacts characterisation of a standard challenge test (FlexMeal) during the second metabolic day : IL6 iAUC
timeFrame: 5 hours post standard challenge test during visit 10
measure: Inflammatory impacts characterisation of a standard challenge test (FlexMeal) during the second metabolic day : IL1Ra iAUC
timeFrame: 5 hours post standard challenge test during visit 10
measure: Inflammatory impacts characterisation of a standard challenge test (FlexMeal) during the second metabolic day : IL18 iAUC
timeFrame: 5 hours post standard challenge test during visit 10
measure: Cardiovascular risk markers characterisation following the intake of a diet either high or low in SDS : MCP1 concentration
timeFrame: After 3 months consumption of the diet
measure: Cardiovascular risk markers characterisation following the intake of a diet either high or low in SDS : sICAM concentration
timeFrame: After 3 months consumption of the diet
measure: Cardiovascular risk markers characterisation following the intake of a diet either high or low in SDS : sVCAM concentration
timeFrame: After 3 months consumption of the diet
measure: Oxydative stress characterisation following the intake of a diet either high or low in SDS : MDA concentration
timeFrame: After 3 months consumption of the diet
measure: Oxydative stress characterisation following the intake of a diet either high or low in SDS : Urinary isoprostanes concentration
timeFrame: After 3 months consumption of the diet
measure: Glycemic profile parameters following the intake of a diet either high or low in SDS during the time course of the study : MAGE
timeFrame: minimum 3 days to a maximum of 6 days of CGMS record
measure: Glycemic profile parameters following the 3 months consumption of a diet either high or low in SDS : MAGE
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Glycemic profile parameters following the intake of a diet either high or low in SDS during the time course of the study : TIR
timeFrame: minimum 3 days to a maximum of 6 days of CGMS record
measure: Glycemic profile parameters following the 3 months consumption of a diet either high or low in SDS : TIR
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Glycemic profile parameters following the intake of a diet either high or low in SDS during the time course of the study : CV
timeFrame: minimum 3 days to a maximum of 6 days of CGMS record
measure: Glycemic profile parameters following the 3 months consumption of a diet either high or low in SDS : CV
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Glycemic profile parameters following the intake of a diet either high or low in SDS during the time course of the study : SD
timeFrame: minimum 3 days to a maximum of 6 days of CGMS record
measure: Glycemic profile parameters following the 3 months consumption of a diet either high or low in SDS : SD
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Glycemic profile parameters following the intake of a diet either high or low in SDS during the time course of the study : MIME
timeFrame: minimum 3 days to a maximum of 6 days of CGMS record
measure: Glycemic profile parameters following the 3 months consumption of a diet either high or low in SDS : MIME
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Glycemic profile parameters following the intake of a diet either high or low in SDS during the time course of the study : MODD
timeFrame: minimum 3 days to a maximum of 6 days of CGMS record
measure: Glycemic profile parameters following the 3 months consumption of a diet either high or low in SDS : MODD
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Glycemic profile parameters following the intake of a diet either high or low in SDS during the time course of the study : CONGA
timeFrame: minimum 3 days to a maximum of 6 days of CGMS record
measure: Glycemic profile parameters following the 3 months consumption of a diet either high or low in SDS : CONGA
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Glycemic profile parameters following the intake of a diet either high or low in SDS during the time course of the study : ADRR
timeFrame: minimum 3 days to a maximum of 6 days of CGMS record
measure: Glycemic profile parameters following the 3 months consumption of a diet either high or low in SDS : ADRR
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Glycemic profile parameters following the intake of a diet either high or low in SDS during the time course of the study : LGBI
timeFrame: minimum 3 days to a maximum of 6 days of CGMS record
measure: Glycemic profile parameters following the 3 months consumption of a diet either high or low in SDS : LGBI
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Glycemic profile parameters following the intake of a diet either high or low in SDS during the time course of the study : HGBI
timeFrame: minimum 3 days to a maximum of 6 days of CGMS record
measure: Glycemic profile parameters following the 3 months consumption of a diet either high or low in SDS : HGBI
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Mean daylong incremental Area Under the Curve (iAUC), measured by CGMS, following the intake of a diet either high or low in SDS during the time course of the study
timeFrame: from 0 min to 360 min postprandial during the CGMS record periods (from visit 3 to visit 4, from visit 6 to visit 7 and from visit 9 to visit 10)
measure: Mean daylong total Area Under the Curve (tAUC), measured by CGMS, following the intake of a diet either high or low in SDS during the time course of the study
timeFrame: from 0 min to 360 min postprandial during the CGMS record periods (from visit 3 to visit 4, from visit 6 to visit 7 and from visit 9 to visit 10)
measure: Compare diabetes follow-up markers during the first metabolic day : HbA1c
timeFrame: At the basal state during visit 3
measure: Compare diabetes follow-up markers following the intake of a diet either high or low in SDS during the time course of the study : HbA1c concentration
timeFrame: At a basal state, during visit 3, visit 6 and visit 10
measure: Compare diabetes follow-up markers following the 3 months consumption of a diet either high or low in SDS : HbA1c concentration
timeFrame: After 3 months consumption of the diet, at the basal state
measure: Compare Diabetes follow-up markers during the first metabolic day : Fructosamine concentration
timeFrame: At the basal state during visit 3
measure: Compare Diabetes follow-up markers following the intake of a diet either high or low in SDS during the time course of the study : fructosamine concentration
timeFrame: At a basal state, during visit 3, visit 6 and visit 10
measure: Compare Diabetes follow-up markers following the 3 months consumption of a diet either high or low in SDS : Fructosamine concentration
timeFrame: After 3 months consumption of the diet, at the basal state
measure: Compare Diabetes follow-up markers during the first metabolic day : Glycated Albumin concentration
timeFrame: At the basal state during visit 3
measure: Compare Diabetes follow-up markers following the intake of a diet either high or low in SDS during the time course of the study : glycated albumin concentration
timeFrame: At a basal state, during visit 3, visit 6 and visit 10
measure: Compare Diabetes follow-up markers following the 3 months consumption of a diet either high or low in SDS : Glycated Albumin concentration
timeFrame: After 3 months consumption of the diet, at the basal state
measure: Arterial Endothelial Function characterisation following the intake of a diet either high or low in SDS during the time course of the study : RHI
timeFrame: At a basal state during visit 4, visit 7 and visit 9
measure: Arterial Endothelial Function characterisation following the intake of a diet either high or low in SDS during the time course of the study : AI
timeFrame: At a basal state during visit 4, visit 7 and visit 9
measure: Arterial Endothelial Function characterisation following the intake of a diet either high or low in SDS during the time course of the study : HRV
timeFrame: At a basal state during visit 4, visit 7 and visit 9
measure: Anthropometry parameters characterisation during the first metabolic day : height
timeFrame: At baseline during visit 3
measure: Anthropometry parameters characterisation during the first metabolic day : body weight
timeFrame: At baseline during visit 3
measure: Anthropometry parameters characterisation during the first metabolic day : waist circumference
timeFrame: At baseline during visit 3
measure: Anthropometry parameters characterisation during the first metabolic day : hip circumference
timeFrame: At baseline during visit 3
measure: Anthropometry parameters characterisation following the intake of a diet either high or low in SDS during the time course of the study : height
timeFrame: At baseline during visit 3, visit 6 and visit 10
measure: Anthropometry parameters characterisation following the intake of a diet either high or low in SDS during the time course of the study : body weight
timeFrame: At baseline during visit 3, visit 6 and visit 10
measure: Anthropometry parameters characterisation following the intake of a diet either high or low in SDS during the time course of the study : waist circumference
timeFrame: At baseline during visit 3, visit 6 and visit 10
measure: Anthropometry parameters characterisation following the intake of a diet either high or low in SDS during the time course of the study : hip circumference
timeFrame: At baseline during visit 3, visit 6 and visit 10
measure: Anthropometry parameters characterisation following the 3 months consumption of a diet either high or low in SDS : height
timeFrame: At baseline during visit 10
measure: Anthropometry parameters characterisation following the 3 months consumption of a diet either high or low in SDS : body weight
timeFrame: At baseline during visit 10
measure: Anthropometry parameters characterisation following the 3 months consumption of a diet either high or low in SDS : waist circumference
timeFrame: At baseline during visit 10
measure: Anthropometry parameters characterisation following the 3 months consumption of a diet either high or low in SDS : hip circumference
timeFrame: At baseline during visit 10
measure: Body composition parameters characterisation during the first metabolic day: total body water
timeFrame: At baseline during visit 3
measure: Body composition parameters characterisation during the first metabolic day: body fat
timeFrame: At baseline during visit 3
measure: Body composition parameters characterisation during the first metabolic day: lean mass.
timeFrame: At baseline during visit 3
measure: Body composition parameters characterisation following the 3 months consumption of a diet either high or low in SDS : total body water
timeFrame: At baseline during visit 10
measure: Body composition parameters characterisation following the 3 months consumption of a diet either high or low in SDS : body fat
timeFrame: At baseline during visit 10
measure: Body composition parameters characterisation following the 3 months consumption of a diet either high or low in SDS : lean mass
timeFrame: At baseline during visit 10
measure: Resting energy metabolism profile during the first metabolic day: Resting Metabolism Rate
timeFrame: At baseline during visit 3
measure: Resting energy metabolism profile following the 3 months consumption of a diet either high or low in SDS : Resting Metabolism Rate
timeFrame: At baseline during visit 10
measure: Diabetic glycemic variability characterisation following the 3 months consumption of a diet either high or low in SDS
timeFrame: after 3 months consumption of the diet, CGMS record for a minimum of 3 days to a maximum of 6 days
measure: Level of physical activity characterisation following the intake of a diet either high or low in SDS during the time course of the study : IPAQ
timeFrame: After each CGMS record periods, ie : at visit 4, visit 7 and visit 10
measure: Characterisation of acceptability to H-SDS diet in free living conditions
timeFrame: After 3 months consumption of the diet, at visit 10
measure: Characterisation of the percent of compliance to H-SDS diet in free living conditions
timeFrame: After 3 months consumption of the diet
Other outcomes:
Locations:
city: Pierre-Bénite
country: France
facility: Centre de Recherche en Nutrition Humaine Rhone-Alpes
Study officials:
affiliation: Centre de Recherche en Nutrition Humaine Rhône-Alpes
name: Emmanuel DISSE, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre de Recherche en Nutrition Humaine Rhône-Alpes
name: Martine LAVILLE, MD, PhD
role: STUDY_CHAIR
References: