NutrImm: The Alberta NutrIMM Study - Nutrition and Immunity

Sponsor

University of Alberta (Other)

Overall Status

Recruiting

CT.gov ID

NCT04291391

Collaborator

Canadian Institutes of Health Research (CIHR) (Other)

132

Enrollment

Location

Arms

51.9

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Excess weight, nutrition, and blood sugar levels can all affect immune function, which in turn can affect participants risk for heart disease and type 2 diabetes (T2DM). It is not known how diet, blood sugar, and weight affect immune function.

The purpose of the study is to look at how weight, diet and high blood sugar levels affect immune function. Results of the study will be compared to results of the control group (which will go through the same activities as the experimental groups).

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2 Obesity	Other: North American Diet	N/A

Detailed Description

Rationale: Obesity is associated with several risk factors (for example, high blood sugar, poor insulin response and inflammation) that increase risk of developing cardiovascular disease and type 2 diabetes (T2DM). Obesity is also associated with abnormalities in the immune system and an increased risk of infection. Specific components of the diet such, as high dietary intake of fat and sugar, influence not only the development of obesity but also the immune system. It is unknown if the immune abnormalities associated with obesity in humans are due to: 1) excess body fat and/or 2) elevated blood sugar levels, often seen in obesity and/or 3) overall diet quality of an individual (for example high fat and/or high sugar intakes).

Research aims: The overall aim of this research proposal is to determine if diet or alterations in blood sugar levels independently affect inflammation and immune function in obese subjects. To achieve this goal, three objectives will be pursued: 1) to determine how obesity affects inflammation and immune function; 2) to determine how alterations in blood sugar levels affect inflammation and immune function; 3) to identify specific dietary factors that affect changes in immune function that are related to obesity.

Methodology: The study will recruit 4 groups of subjects that are similar in age and sex:

lean subjects with normal blood sugar levels (NG); obese subjects with normal blood sugar levels (obese-NG); obese subjects who are pre-diabetic (as defined by having high blood sugar levels - but not high enough to be defined as having diabetes; GI); obese subjects who have type 2 diabetes (obese-T2DM).

Participants will consume a typical North American/Canadian diet that will maintain their weight for a 4-week time period (all food will be provided for the subjects by the Human Nutrition Clinical Research Unit at the University of Alberta). Immune system markers (inflammation in the blood and the response of immune cells) and cardiovascular disease markers (blood sugar and insulin) will be compared among the 4 groups of participants before and at the end of the study.

A stool sample will also be collected before and after the diet intervention to look at the effects of weight and blood sugar levels on the type of bacteria in the participants gut as part of a Stool Sub-study. Research has shown that weight and blood sugar levels may affect the type of bacteria in the participants gut, which in turn can affect immune function and health risk. This is not a part of the main study, and the participants stool sample will be analyzed in future research.

Outcomes: By comparing these four groups, the investigators will be able to gain an understanding of the immune complications associated with obesity alone (ie excess body fat) and the relationship between blood sugar levels and diet with immune complications. Thus, this study will identify dietary interventions to counteract the immune abnormalities associated with obesity, which may in turn have implications for affecting the risk of cardiovascular disease and T2DM associated with obesity.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

132 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

4-parallel arm study4-parallel arm study

Masking:

Single (Participant)

Masking Description:

Participants are blinded to which group they are assigned to.

Primary Purpose:

Other

Official Title:

The Alberta NutrImm Study (Nutrition and Immune Function) Study: Establishing the Importance of Diet and Insulin Resistance in Modulating Immune Function in Obesity

Actual Study Start Date :

Sep 1, 2019

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lean-normoglycemic (control) All groups will consume a standardized North American/Canadian diet for 4 weeks designed to reflect (as closely as possible) current macronutrient intake averages in North America/Canada (35% of energy as fat, 12.5% as saturated fat, 13% as monounsaturated fat, 6% as polyunsaturated fat, 48% as carbohydrate, 17% as protein).	Other: North American Diet standardized North American/Canadian diet for 4 weeks designed to reflect (as closely as possible) current macronutrient intake averages in North America/Canada (35% of energy as fat, 12.5% as saturated fat, 13% as monounsaturated fat, 6% as polyunsaturated fat, 48% as carbohydrate, 17% as protein)
Experimental: Obese - normoglycemic All groups will consume a standardized North American/Canadian diet for 4 weeks designed to reflect (as closely as possible) current macronutrient intake averages in North America/Canada (35% of energy as fat, 12.5% as saturated fat, 13% as monounsaturated fat, 6% as polyunsaturated fat, 48% as carbohydrate, 17% as protein).	Other: North American Diet standardized North American/Canadian diet for 4 weeks designed to reflect (as closely as possible) current macronutrient intake averages in North America/Canada (35% of energy as fat, 12.5% as saturated fat, 13% as monounsaturated fat, 6% as polyunsaturated fat, 48% as carbohydrate, 17% as protein)
Experimental: obese-glucose intolerant All groups will consume a standardized North American/Canadian diet for 4 weeks designed to reflect (as closely as possible) current macronutrient intake averages in North America/Canada (35% of energy as fat, 12.5% as saturated fat, 13% as monounsaturated fat, 6% as polyunsaturated fat, 48% as carbohydrate, 17% as protein).	Other: North American Diet standardized North American/Canadian diet for 4 weeks designed to reflect (as closely as possible) current macronutrient intake averages in North America/Canada (35% of energy as fat, 12.5% as saturated fat, 13% as monounsaturated fat, 6% as polyunsaturated fat, 48% as carbohydrate, 17% as protein)
Experimental: obese with type 2 diabetes All groups will consume a standardized North American/Canadian diet for 4 weeks designed to reflect (as closely as possible) current macronutrient intake averages in North America/Canada (35% of energy as fat, 12.5% as saturated fat, 13% as monounsaturated fat, 6% as polyunsaturated fat, 48% as carbohydrate, 17% as protein).	Other: North American Diet standardized North American/Canadian diet for 4 weeks designed to reflect (as closely as possible) current macronutrient intake averages in North America/Canada (35% of energy as fat, 12.5% as saturated fat, 13% as monounsaturated fat, 6% as polyunsaturated fat, 48% as carbohydrate, 17% as protein)

Outcome Measures

Primary Outcome Measures

Obesity-related immune dysfunction and Inflammation measured by blood Immune Markers [4 weeks]
In the fasting state, immune cell subset frequencies will be determined by flow cytometry to quantify various immune cell phenotypes (type and activation). Immune cells will be stained for T cell (CD3, CD4+, CD8+, CD45RA+, CD45RO+), Treg (FOXP3+), B cell (CD19, CD20), macrophage (CD14, CD64), NK cell (CD56+) and activation markers (CD11b+, CD25+, CD28+, CD80+, CD127+, CD152+, CD278+). All samples will be acquired by flow cytometry and analyzed according to the relative fluorescence intensity using Kaluza Software. In the fasting and postprandial states, cell proliferation will be measured by flow cytometry using eBioscience Dye eFluor 670 and intracellular cytokines accumulation in different immune cell types will be determined using commercially available human intracellular staining kits and quantified by flow cytometry as above.

Secondary Outcome Measures

Glycemia after an oral glucose tolerance test by measuring blood Glucose levels [4 weeks]
Assess Glucose levels over duration of 3 hour Oral Glucose Tolerance Test collecting blood samples at 0, 30, 60, 90, 120, 150 and 180 minutes. Plasma glucose will be measured as per the glucose oxidase method.
Glycemia after an oral glucose tolerance test by measuring blood Insulin levels [4 weeks]
Assess Insulin levels over duration of 3 hour Oral Glucose Tolerance Test collecting blood samples at 0, 30, 60, 90, 120, 150 and 180 minutes. Plasma insulin will be determined using commercially available enzymatic immunoassays (ELISA) to compute the insulin resistance index HOMA.
Change in Dietary Intake between Baseline Values and the control menu. [4 weeks]
A validated food frequency questionnaire for Canadians (Canadian Diet History Questionnaire II (CDHQII)) will be administered to participants before the start of the study in order to better accurately assess/estimate their habitual diet
Change in dietary factors will be assessed using: the change in fatty acid composition of PBMC [4 weeks]
Total lipids in plasma, Red Blood Cells and PBMCs (Peripheral blood mononuclear cell) membranes will be extracted using Folch ratio 4:1 (chloroform:methanol (2:1): KCl). Fatty acid methyl esters will be measured by automated gas liquid chromatography using a 100m CP-Sil 88 fused capillary column. Total phospholipids and lipid classes in PBMCs membrane will be quantified using thin-layer chromatography and identified using internal standards. Total PC, PE and PS in PBMCs membrane will be quantified using HILIC liquid chromatography-tandem mass spectrometry (LC-MS/MS) using an Agilent 1200 series HPLC system coupled to a 3200 QTRAP mass spectrometer.

Other Outcome Measures

Gut microbiota composition by using DNA Sequencing [4 weeks]
We will utilize illumina 16S rRNA sequencing and whole metagenomics sequencing to characterize the fecal microbiota (that will be enriched for large bowel bacteria) of our clinical participants pre- and post-diet intervention, to explore if a typical Canadian diet, induces changes in gut microbiota composition and gene content in obese, insulin resistant, and diabetic subjects. These methods will be used as a majority of microbiota are not currently culturable.
Assess correlations between clinical outcomes and microbiome to identify interactions and microbiome signatures that predict how diet may impact these indicators in obese, insulin resistant, and diabetic subjects. [4 weeks]
Assess correlations between clinical outcomes and microbiome configurations to identify mechanistic interactions and microbiome signatures that predict how a typical Canadian diet may impact these indicators in obese, insulin resistant, and diabetic subjects

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Men and women 18-65 years old that are lean (BMI < 25 kg/m2) and obese (BMI > 30 kg/m2) will be recruited in the Edmonton area.
Waist circumference (cm) criteria: A waist circumference of 102 cm or more in men, or 88cm in women, is associated with health problems such as type 2 diabetes.
Fasting blood glucose levels: lean-NG and obese-NG will have values less than 5.6 mmol/L, Obese-GI will have levels greater than 5.6 mmol/L, but less than 7 mmol/L; and obese-T2DM will have levels greater than or equal to 7 mmol/L.
HbA1c levels: lean-NG and obese-NG will have levels less than 5.6%; obese-GI will have levels greater than 5.6% but less than 6.5%; obese-T2DM will have levels greater than or equal to 6.5%, but less than 10%.
Blood Pressure criteria: lean-NG and obese-NG as being healthy, a blood pressure criterion of less than 130/85 mmHg will be required (represents systolic pressure/diastolic pressure).
Triglycerides (TGs) and high density lipoprotein cholesterol (HDL-C): Lean-NG and obese-NG subjects will have TG levels less than 1.7 mmol/L, and HDL-C levels greater than 1.03 mmol/L for men and greater than 1.29 mmol/L for women.

Exclusion Criteria:

Health status: individuals with a previous history of cardiovascular disease, renal disorder, monogenic dyslipidemia, presence of an endocrine disorder other than T2DM
Diabetes: newly diagnosed individuals (< 6 months) or those with poorly controlled (HbA1C > 8.0%) diabetes
Pregnant or lactating women:
individuals taking chronic anti-inflammatory drugs or supplements (including aspirin, antihistamines and omega-3 supplements)
Smokers:
men and women whose body weight has not been stable for at least 6 months prior to the study
Participants who cannot comply to greater than or equal to 90% of the feeding protocol
If a potential participant has many food allergies, where the allergic reaction is potentially life threatening
Pacemaker or internal electrical device