The Alberta NutrIMM Study - Nutrition and Immunity
- Conditions
- ObesityDiabetes Mellitus, Type 2
- Interventions
- Other: North American-type diet
- Registration Number
- NCT04291391
- Lead Sponsor
- University of Alberta
- Brief Summary
This study will investigate the effect of body weight, diet, and high blood sugar levels, under controlled feeding conditions, on immune function in individuals with and without obesity.
This study will be a non-randomized, four-arm parallel group, clinical trial under controlled feeding conditions (4-week nutritional intervention using a North American-type diet). A sample size of n=128 participants will be allocated into one of the following groups:
* Individuals without obesity and normoglycemia (NG) (Lean-NG)
* Individuals with obesity and normoglycemia (Obese-NG)
* Individuals with obesity and glucose intolerance (GI) (Obese-GI)
* Individuals with obesity and type 2 diabetes (T2D) (Obese-T2D)
The following outcomes will be analyzed:
* Immune cell function (ex-vivo cytokine production after stimulation with mitogen and T cell proliferation);
* Immune cell phenotypes;
* Systemic inflammation (C-reactive protein and plasma cytokines);
* Glucose, insulin, glycated hemoglobin (HbA1c), and lipids;
* Fatty acids and phospholipds composition in plasma and red blood cells membrane.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 114
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Individuals with obesity and type 2 diabetes (T2D) (Obese-T2D) North American-type diet Those assigned to the Obese-T2D group will receive a North American-type diet diet for 4 weeks. Individuals with obesity and NG (Obese-NG) North American-type diet Those assigned to the Obese-NG group will receive a North American-type diet diet for 4 weeks. Individuals with obesity and glucose intolerance (GI) (Obese-GI) North American-type diet Those assigned to the Obese-GI group will receive a North American-type diet diet for 4 weeks. Individuals without obesity and normoglycemia (NG) (Lean-NG) North American-type diet Those assigned to the Lean-NG group will receive a North American-type diet diet for 4 weeks.
- Primary Outcome Measures
Name Time Method Differences between groups in circulating C-reactive protein (CRP) at Week 4 Week 4 CRP will be measured by Alberta Precision Labs using an immunoturbidimetric assay
Differences between groups in IL-2 Secretion by Peripheral Blood Mononuclear Cells (PBMC) After Ex-vivo Stimulation with Phytohemagglutinin (PHA) at Week 4 Week 4 PBMCs will be stimulated with PHA for 48h and IL-2 will be quantified using enzyme-linked immunosorbent assay (ELISA).
- Secondary Outcome Measures
Name Time Method Change from Baseline in IL-2 Secretion by PBMC After Ex-vivo Stimulation with mitogens at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 PBMCs will be stimulated with Pokeweed Mitogen (PWM) and Phorbol Myristate Acetate and Ionomycin (PMAi), for 48h and IL-2 will be quantified using ELISA
Change from Baseline in IL-6 Concentrations at Week 4 and Differences Between Groups at Baseline and Week 4. Baseline and Week 4 IL-6 will be quantified using a multiplex assay (mesoscale).
Change from Baseline in IL-10 Secretion by PBMC After Ex-vivo Stimulation with mitogens at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 PBMCs will be stimulated with PHA, LPS, PWM, and PMAi for 48h and IL-10 will be quantified using ELISA
Change from Baseline in TNF-a Concentrations at Week 4 and Differences Between Groups at Baseline and Week 4. Baseline and Week 4 TNF-a will be quantified using a multiplex assay (mesoscale).
Change from Baseline in IL-1B Secretion by PBMC After Ex-vivo Stimulation with mitogens at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 PBMCs will be stimulated with Lipopolysaccharides (LPS) and PWM for 48h and PBMCs will be stimulated with PHA, LPS, PWM, and PMAi for 48h and IFN-y will be quantified using ELISA
Change from Baseline in IFN-y Secretion by PBMC After Ex-vivo Stimulation with mitogens at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 PBMCs will be stimulated with PHA, LPS, PWM, and PMAi for 48h and IFN-y will be quantified using ELISA
Change from Baseline in T cell proliferation at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 PBMCs will be stimulated with anti-CD3/anti-CD28 for 72h and proliferation will be quantified using alamarBlue dye method, which is a reliable and sensitive assay
Change from Baseline in T Cells at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Immune cell phenotype of T cells will be determined using immunofluorescence staining for flow cytometry. The following monoclonal antibodies will be used: CD3, CD4, CD8, CD25, CD28, CD45RA, CD45RO, CTLA-4 (CD152), CD192, FoxP3, CD183, CD194, CCR10, CD196, and CD185. Data visualization will be performed in FlowJo software
Change from Baseline in Circulating Glucose Levels at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Glucose will be measured by Alberta Precision Labs with an UV testing using an enzymatic reference method with hexokinase
Change from Baseline in Circulating Low-Density Lipoprotein Cholesterol Levels at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 LDL-C is calculated using the following equation: \[Total cholesterol - HDLc - (Triglycerides/2.2)\]
Change from Baseline in TNF-a Secretion by PBMC After Ex-vivo Stimulation with mitogens at Week 4 and Differences Between Groups at Baseline and Week 4. Baseline and Week 4 PBMCs will be stimulated with PHA, LPS, PWM, and PMAi for 48h and TNF-a will be quantified using ELISA
Change from Baseline in IL-6 Secretion by PBMC After Ex-vivo Stimulation with mitogens at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 PBMCs will be stimulated with PHA, LPS, PWM, PMAi for 48h and IL-6 will be quantified using ELISA
Change from Baseline in B Cells at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Immune cell phenotype of B cells will be determined using immunofluorescence staining for flow cytometry. The following monoclonal antibodies will be used: CD19, CD20, ICAM-1 (CD54), CD80, and CD192. Data visualization will be performed in FlowJo software.
Change from Baseline in Dendritic Cells at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Immune cell phenotype of dendritic cells will be determined using immunofluorescence staining for flow cytometry. The following monoclonal antibodies will be used: CD11c, CD80, CD213, CD273, and HLA-DR. Data visualization will be performed in FlowJo software
Change from Baseline in Natural Killer Cells at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Immune cell phenotype of T cells will be determined using immunofluorescence staining for flow cytometry. The following monoclonal antibodies will be used: CD3, CD16, and CD56. Data visualization will be performed in FlowJo software
Change from Baseline in Circulating Insulin Levels at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Insulin will be measured by Alberta Precision Labs using an electrochemiluminescence immunoassay
Change from Baseline in Circulating Triglycerides Levels at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Triglycerides will be measured by Alberta Precision Labs using an enzymatic colorimetric assay
Change from Baseline in Circulating Hemoglobin A1c Levels at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 HbA1c will be measured by Alberta Precision Labs using a turbidimetric inhibition immunoassay for hemolyzed whole blood
Change from Baseline in Monocytes at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Immune cell phenotype of Monocytes will be determined using immunofluorescence staining for flow cytometry. The following monoclonal antibodies will be used: CD11c, CD14, ICAM-1 (CD54), CD80, CD86, CD273, and HLA-DR. Data visualization will be performed in FlowJo software
Change from Baseline in Complete Blood Cell Count and Differential at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Blood count and differential will be analyzed by Alberta Precision Labs in whole blood by fluorescent flow cytometry using a semi-conductor laser and hydrodynamic focusing in dedicated channels using an automated hematology analyzer
Change from Baseline in Phospholipids Classes Quantifications in Red Blood Cells at Week 4 and Differences Between Groups at Baseline and Week 4. Baseline and Week 4 Quantification of phospholipds will be determined by high performance liquid chromatography
Differences Between Groups at Week 4 in Circulating Glucose Levels before and after an Oral Glucose Tolerance Test Week 4 Blood will be collected at the following time points after consuming the glucose solution: 0, 30, 60, 90, 120, 150, and 180 minutes. Plasma glucose concentrations will be measured using the hexokinase/glucose-6-phosphate dehydrogenase method using a clinical chemistry analyzer
Change from Baseline in Total Lipids Fatty Acids Composition in Plasma and Red Blood Cells at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Proportion of fatty acids will be determined using gas chromatography
Change from Baseline in Circulating Total Cholesterol Levels at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Total Cholesterol will be measured by Alberta Precision Labs using an enzymatic colorimetric assay
Change from Baseline in Phospholipids Fatty Acids Composition in Red Blood Cells at Week 4 and Differences Between Groups at Baseline and Week 4. Baseline and Week 4 Proportion of fatty acids from phospholipids will be determined using gas chromatography
Change from Baseline in Circulating High-Density Lipoprotein Cholesterol Levels at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 High-Density Lipoprotein Cholesterol will be measured by Alberta Precision Labs using an enzymatic colorimetric assay
Change from Baseline in Circulating Non-High Density Lipoprotein Cholesterol Levels at Week 4 and Differences Between Groups at Baseline and Week 4 Baseline and Week 4 Non-HDL c is derived from the calculation of total cholesterol minus HDL-c
Trial Locations
- Locations (1)
University of Alberta
🇨🇦Edmonton, Alberta, Canada