Clinical trial NCT03235804: The Impact of a Powdered Meal Replacement on Metabolism and Gut Microbiota
Official title: The Impact of a Powdered Meal Replacement on Metabolism and Gut Microbiota: a 12-week Study in Individuals With Excessive Body Weight
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dietary Modification
Keywords: Powdered meal replacement
Inflammation
Gut microbiota
Energy metabolism
Body composition
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: Almased Wellness GmbH
First posted: 2017-08-01
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study will investigate the impact of a 12-week powdered meal replacement on inflammatory, metabolic, and hormonal markers of obesity-associated conditions and to correlate this response to compositional shifts within the gut microbiota. Moreover, resting energy expenditure, body composition, appetite sensations and soy metabolomics will be explored.

This study will be a randomized, parallel group, clinical trial of a 12-week nutritional intervention. A sample size of n=88 participants will be randomly allocated into one of the following groups:

* Control group (CON): Participants will be asked to maintain their usual dietary intake over 12 weeks. Their usual dietary intake is expected to reflect the North American dietary pattern (i.e. \~15% of total energy intake coming from protein, \~50% from carbohydrate and \~35% from fat).
* Powdered Meal Replacement group (PMR): Participants will be asked to maintain their usual dietary intake and consume a powdered meal replacement composed of soy protein, honey and yogurt twice daily (in two snacks) over 12 weeks. The addition of the meal replacement to a North American Dietary Pattern (described on the CON group diet) will result in a diet composed of, approximately, 22% of protein, 48% of carbohydrate and 30% of fat of total energy intake.

The following variables will be analyzed:

* Interleukin (IL)-6.
* Gut microbiota diversity and composition, specifically taxa that have been associated with health benefits, obesity, and weight loss.
* Systemic inflammatory biomarkers (high-sensitivity C-reactive protein, IL-8, IL-10 and tumor necrosis factor-α);
* Metabolic blood markers (glucose, insulin, lipid panel, peptide tyrosine-tyrosine, glucagon-like peptide-1, ghrelin, adiponectin, leptin, free glycerol, free fatty acids, and thyroid stimulating hormone)
* Resting energy expenditure;
* Body composition;
* Appetite sensations (hunger, satiety, fullness, and prospective food consumption);
* Soy polyphenols' metabolomics.
* Gene expression and genetic polymorphisms. At baseline and after 6 and 12 weeks, individuals will attend our Human Nutrition Research Unit where all assessments will take place. In order to assess participants' adherence and follow-up, dietary intake, body weight and appetite sensations (only for participants assigned to the PMR group) will be assessed weekly during the 12-week intervention period. Additionally, participants will be contacted by phone weekly and reminded to maintain their journal/log.

Detailed description: Overweight and obesity increase the risk of developing several diseases having a negative effect on people's health. The prevalence of these conditions is increasing worldwide, but successful treatments are lacking. As excess body weight is a result of an imbalance between calories in and calories out, dietary intake plays an important role in maintaining a healthy body weight and overall health status. Meal replacements are nutritionally complete formula foods used to substitute a meal. They can be a drink, bar, or soup. These products have been gaining popularity because they can help individuals lose weight. In addition, depending on its ingredients, meal replacements may affect our health. For this reason, meal replacements have been studied for health benefits. However, how meal replacements affect the microbes living in our gut, inflammation, and our genes is not known. Well-designed studies using state-of-the-art equipment can help elucidate the mechanisms by meal replacements act in individuals with overweight or obesity.

The overall purpose of this research is to investigate the impact of a 12-week powdered meal replacement on inflammatory, metabolic, and hormonal markers of obesity-associated conditions and to correlate this response to compositional shifts within the gut microbiota. Moreover, resting energy expenditure, body composition, appetite sensations, soy metabolomics, gene expression, and genetic polymorphisms will be explored.

This study will be a randomized, parallel group, clinical trial of a 12-week nutritional intervention. A sample size of n=88 participants will be randomly allocated into one of the following groups:

* Control group (CON): Participants will be asked to maintain their usual dietary intake over 12 weeks. Participants' usual dietary intake is expected to reflect the North American dietary pattern (i.e. \~15% of total energy intake coming from protein, \~50% from carbohydrate and \~35% from fat).
* Powdered Meal Replacement group (PMR): Participants will be asked to maintain their usual dietary intake and consume a powdered meal replacement composed of soy protein, honey and yogurt twice daily (in two snacks) over 12 weeks. The addition of the nutritional supplement to a North American Dietary Pattern (described on the CON group diet) will result in a diet composed of, approximately, 22% of protein, 48% of carbohydrate and 30% of fat of total energy intake. The amount of protein is considered higher than the North American dietary pattern (i.e. 15%); however, still within the Acceptable Macronutrient Distribution Range (AMDR) recommended by the Dietary Guidelines for Americans (10-35%).

The following variables will be analyzed:

* Interleukin (IL)-6.
* Gut microbiota diversity and composition, specifically taxa that have been associated with health benefits, obesity, and weight loss.
* Systemic inflammatory biomarkers (high-sensitivity C-reactive protein \[hs-CRP\], IL-8, IL-10 and tumor necrosis factor-α \[TNF-α\]);
* Metabolic blood markers \[glucose, insulin, lipid panel (i.e. total cholesterol, LDL, HDL, and triglycerides), peptide tyrosine-tyrosine (PYY), glucagon-like peptide-1 (GLP-1), ghrelin, adiponectin, leptin, free glycerol, free fatty acids, and thyroid stimulating hormone (TSH)\];
* Resting energy expenditure;
* Body composition;
* Appetite sensations (hunger, satiety, fullness, and prospective food consumption);
* Soy polyphenols' metabolomics.
* Gene expression and genetic polymorphisms. At baseline and after 6 and 12 weeks, individuals will attend our Human Nutrition Research Unit where all assessments will take place. In order to assess participants' adherence and follow-up, dietary intake, body weight and appetite sensations will be assessed weekly during the 12-week intervention period. Additionally, participants will be contacted by phone weekly and reminded to maintain their journal/log. Dietary intake will be assessed by a 3-day dietary record (2 week days and 1 weekend day) at baseline, at mid-point and end of the study. Participants will also be asked to complete a 1-day dietary record on one weekday, each week of the study. The purpose of this regular assessment is to avoid daily fluctuations in eating patterns, also ensuring a personalized feedback for those experiencing weight fluctuations. Both of these assessments (i.e. 1-day and 3-day dietary records) will be conducted using the online Automated Self -Administered 24-hour Recall (ASA24) Canada. The ASA24 is a validated web-based program that uses the validated U.S. Department of Agriculture's Automated Multiple-Pass Method, and is modified to support the Canadian food supply.

Participants will receive a digital scale and will be asked to weight themselves daily. Participants from the PMR group will also be asked to rate their appetite sensations on a 100-mm VAS paper sheet. Appetite sensation should be completed in the morning (after waking up and while fasting) and 30 minutes after consuming the supplement snacks in order to assess hunger, satiety, fullness, and prospective food consumption.

Eligibility criteria: Inclusion Criteria:

* Non-smoker;
* Female/Male;
* Aged 18 to 50 years;
* Body mass index (BMI) between 25 and 37 kg/m²;
* Weight stable (\< ± 5 kg over past 6 months);
* Fat mass ≥20% for men and ≥25% for women;
* Maintaining current levels of physical activity throughout the study.
* Female participants must verify use of acceptable, effective birth control methods (total abstinence, hormonal birth control \[oral, injectable, transdermal, intravaginal\], intrauterine devices, confirmed successful vasectomy or partner, or condoms).

Exclusion Criteria:

* Diagnosis of chronic diseases or acute infections;
* Taking any medication that may alter inflammation, energy metabolism, body weight and composition, gut microbiota and hormone levels; investigators should always be informed if there are any changes in medications or Natural health product use;
* Taking pre- and probiotics (e.g. supplements);
* Use of antibiotics in the past two months;
* Use of thyroid replacement therapy;
* Use of nutritional supplements in the past four weeks (multivitamin and vitamin D3 are permitted to be used during the course of the study);
* Allergy to any ingredient (including non-medicinal ingredients) in investigational product;
* Lactose, gluten and/or soy allergic/intolerant;
* Follow a vegetarian, vegan or any restrictive dietary pattern;
* Pregnant or lactating;
* Perform over three hours of vigorous physical activity per week;
* A nuclear medicine scan or injection of an X-ray dye in the past week;
* A barium test/exam in the last two weeks;
* Suffer from claustrophobia;
* Inability to comprehend and complete the required questionnaires.

Primary outcomes:
measure: Interleukin-6.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
Secondary outcomes:
measure: Gut microbiota diversity and composition.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
Other outcomes:
measure: High-sensitivity C-reactive protein.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Interleukin 8.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Interleukin 10.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Tumor necrosis factor-α.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Adiponectin.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Blood glucose.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Insulin.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Lipid panel.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Peptide tyrosine-tyrosine.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Glucagon-like peptide 1.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Ghrelin.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Leptin.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Free glycerol.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Free fatty acids.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Thyroid stimulating hormone.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Resting energy expenditure.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Body composition.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Appetite sensations.
timeFrame: Once per week during the intervention period (12 weeks).
measure: Soy polyphenols' metabolomics.
timeFrame: At baseline (week 1), middle (week 6) and end (week 12) of the intervention period (12 weeks).
measure: Gene expression
timeFrame: At baseline (week 1) and end (week 12) of the intervention period (12 weeks).
measure: Genetic polymorphisms
timeFrame: At baseline (week 1)
Locations:
city: Edmonton
country: Canada
facility: Human Nutrition Research Unit
state: Alberta
Study officials:
affiliation: University of Alberta
name: Jens Walter, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Carla M Prado, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Arya Sharma, PhD
role: PRINCIPAL_INVESTIGATOR
References: