Clinical trial NCT04120051: The SIMBA Project - The Effect of a Prebiotic Supplement on Glucose Metabolism and Gut Microbiota in Obese Adults
Official title: The SIMBA Project - The Effect of a Prebiotic Supplement on Glucose Metabolism and Gut Microbiota
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Glucose Metabolism
Metabolic Syndrome
Gut Microbiota
Keywords: Gut Microbiota
Metabolic syndrome
Obesity
Supplement
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: FermBiotics ApS
First posted: 2019-10-09
Enrollment: 100
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The participants will be randomized to the Fermented Canola-Seaweed supplement or control and are expected to consume one sachet (5 grams) of either every day for 6 weeks
Primary purpose: OTHER

Brief summary: Modulation of the gut microbiota via administration of pro- and prebiotics have been proposed to contribute to weight loss and reduce plasma glucose and serum lipid levels, improving the inflammatory state and decreasing the incidence of type 2 diabetes and cardiovascular disease. This study will test a fermented canola-seaweed (FCS) product, high in glucosinolates and putatively prebiotic oligosaccharides, in human subjects with obesity.

Detailed description: The overall objective of this study is to investigate a fermented canola-seaweed (FCS) product in obese human subjects with increased risk of metabolic syndrome (MS). We will study the effects of the FCS on glucose handling and related cardiometabolic traits such as dyslipidemia and low-grade systemic inflammation. Finally, we will examine the gut microbiota and the metabolic phenotype of the subjects to explore molecular mechanisms related to the potential improvements.

It is hypothesized that the FCS product will improve postprandial glucose handling, blood lipids and low-grade inflammation in obese subjects with increased risk of MS. Furthermore, it is hypothesized that this effect is modified through gut microbiota compositional and functionality changes

Methods:

This study will be conducted as a randomized, controlled, investigator and participant blinded intervention trial. The participants will be randomized to the FCS supplement or control and are expected to consume one sachet of either every day for 6 weeks.

Randomization, blinding and allocation concealment:

After having given oral and written consent, randomization will be performed separately for each participant in blocks of variable size to ensure equal randomization throughout the enrolment phase of the study. The randomization sequence will be done by an investigator without contact to the participants. The personnel conducting the study will allocate participants to the sequence of intervention using a list of participant identification numbers matched with allocated sequences. The participants will be blinded to the intervention and blinding of the allocation sequence will be present for investigators during sample analysis and initial data analysis.

Examinations:

Participants will arrive for clinical examination after an overnight fast of at least 8 hours. Lifestyle questionnaires and questionnaires about medication use will be performed for baseline characterization of the participants. Blood pressure and anthropometric measurements are performed including measurements of body weight, height, waist and hip circumference, and bio-impedance measurements for assessing body fat mass. A fasting blood sample is obtained and an oral glucose tolerance test (OGTT) is performed with collection of blood samples after 0, 30 and 120 min. Samples will be analyzed with standard clinical procedures for glycaemic variability markers, including glucose, insulin, c-peptide, and HbA1c, as well as plasma lipids. Furthermore, fecal samples will be collected at both examination visits and kept stored for future microbiota analyses, using untargeted shotgun sequencing.

Samples in biobank will be stored for further analyses, which could include gastrointestinal hormones, gut microbiota metabolites, blood, and fecal metabolome and low-grade inflammation markers. In addition, a subgroup of participants (10 in each group) will be equipped with a 24-h continuous glucose monitoring device for 14 days at the start of the intervention period. Both examination days consists of similar examinations and data collections and are estimated to last approximately 2½ hours.

Eligibility criteria: Inclusion Criteria:

* Participants who have provided written informed consent
* Age between 30 and 65 years
* Body mass index ≥31 kg/m\^2

Exclusion Criteria:

* Body mass index \<31 kg/m\^2
* Diagnosis of diabetes (HbA1c ≥ 6,5% (48 mmol/mol)) or pharmacological treatment of diabetes
* Use of peroral glucocorticoids
* Lack of compliance with the procedures (ingestion of sachets) in the study protocol, judged by Investigator
* Ingestion of pre- or probiotic supplements during the study and 14 days prior to study start
* Use of systemic antibiotics 1 month prior to study start
* Use of cholesterol lowering drugs
* Have had an obesity or abdominal surgery
* Chronic inflammation disorders (excluding obesity)
* Diagnosed psychiatric disorder including depression requiring treatment
* Gastro intestinal and liver disorders
* Gluten intolerance
* Maltodextrin intolerance
* Intensive physical training/ elite athlete (\>10 hours of strenuous physical activity per week)
* Pregnant or lactating
* High intake of alcohol (\>14 drinks/week for women and \>21 drinks/week for men)
* Simultaneous blood donation for other purpose than this study
* Simultaneous participation in other clinical intervention studies
* Inability, physically or mentally, to comply with the procedures required by the study protocol as evaluated by the principal investigator or clinical responsible.

Primary outcomes:
measure: changes in 2-h post-OGTT glucose in blood between baseline and endpoint
timeFrame: Week 0 and Week 6
Secondary outcomes:
measure: Changes in Hba1c between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Changes in fasting blood glucose between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Changes in 30 min post OGTT between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Insulin sensitivity and secretion
timeFrame: Week 0 and Week 6
measure: Changes in blood lipids between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Changes in C-Reactive Protein between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Changes in Interleukin-6 between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Changes in small metabolites between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Changes in weight between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Changes in waist circumference between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Changes in body composition between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Changes in blood pressure (BP) between baseline and endpoint
timeFrame: Week 0 and Week 6
measure: Continuous glucose monitoring
timeFrame: Week 0
measure: Changes in Liver function markers
timeFrame: Week 0 and week 6
measure: Changes in circulating endotoxin/lipopolysaccharide (LPS) concentrations
timeFrame: Week 0 and Week 6
measure: Changes in gut microbiota composition
timeFrame: Week 0 and Week 6
Other outcomes:
Locations:
city: Frederiksberg
country: Denmark
facility: University of Copenhagen
state: Danmark
Study officials:
affiliation: University of Copenhagen, Department of Nutrition, Exercise and Sports
name: Mads V Lind, PhD
role: PRINCIPAL_INVESTIGATOR
References: