Saskatoon Berry on Metabolism and Gut Microbiota in Healthy Subjects

Study Overview
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Brief Summary
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Diabetes becomes epidemic in worldwide countries. Nine out of ten diabetic patients are type 2 diabetes (T2D). T2D is characterized by insulin resistance and obesity. Uncontrolled diabetes leads to serious consequences including heart attack, stroke, chronic renal failure, liver failure, blindness and low limb amputation. Most of hypoglycemic medications have side effects. Natural foods or nutraceuticals with hypoglycemic potential are expected to provide a safer management for diabetic patients. Saskatoon berry is a popular fruit in Canadian Prairie and Northern states in USA. Our recent studies demonstrated Saskatoon berry powder (SBp) attenuated hyperglycemia, hyperlipidemia, insulin resistance, inflammation, liver steatosis and gut dysbiosis in diet-induced insulin resistant mice, a model for T2D. The results in antidiabetic activities of SBp have been supported by other groups in high fat fed rats. The combination of findings suggest that Saskatoon berry is good candidate of prebiotic functional food as a supplemental remedy for reducing insulin resistance, metabolic syndrome and preventing or managing T2D. The effect of Saskatoon berry and its products on metabolic disorders have not been studied in human subjects. We propose to examine the effect of oral administration of freeze-dried Saskatoon berry on glucose metabolism, insulin resistance and gut microbiota in healthy adults in a pilot trial.

Detailed Description
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Subject recruitment: Healthy subjects (males and females, 18-75 years of age) in Winnipeg, who are voluntarily signing an informed consent approved by Research Ethics Board in University of Manitoba, will be eligible to the study. Exclusion criteria include: 1) candidates have a history of myocardial infarction, stroke, hypertension, diabetes, hyperlipidemia, chronic kidney disease; 2) participants are taking hypoglycemic, anti-hypertensives, lipid lowering medications or antibiotics within a month. Dietary product: Freeze dried Saskatoon berry have been obtained from Prairie Berries Inc. The berries were freshly frozen and no any supplementation was added to the dried berry. The product has been processed by certified facilities and the batch of dried berry has passed pathogen analysis. Regimen: Participants (n=20) will orally administrate 30 g/day of freeze dried Saskatoon berry during breakfast for 10 weeks. Scheduled visits: Visit 1: Consent and enrollment. A questionnaire for domestic questionnaire including dietary intake and physical activity will be filled. Measurements of body weight, height and blood pressure will be taken during the visit. Visit 2 (<1 week from the visit 1 and before the start of berry administration): 75 g oral glucose tolerance test (OGTT) after an overnight fasting. Insulin, liver enzymes (alanine transaminase or ALT, aspartate transaminase or AST), creatinine, lipid profile and inflammation markers (e. x. tumor necrosis factor-alpha or TNF-alpha) will be measured as baseline. Participants will be provided with sealed packages of dried Saskatoon berry and instruction of the administration. Insulin and lipid profile will be tested in blood samples withdrawn at fast glucose for OGTT. Visit 3 (at 5 weeks after the start of administration of Saskatoon berry): Participants will be asked to provide feedback on general well-being and the intake of Saskatoon berry. Body weight, blood pressure and heart rate will be measured and recorded. Visit 4 (at 10 weeks after the start of the dietary regimen): Participants will be asked to collect stool sample with the collection kit within 1 week before the visit and bring it to the visit. They will also be asked to have an overnight fasting the night before visit. They will receive an OGTT. Blood samples for insulin, liver enzymes, creatinine, lipid profile and inflammation markers will be collected from each participant. During the visit, body weight, blood pressure and heart rate of participants will be taken. Questionnaires on participants' dietary intake, physical activity and feedback to the study will be completed. Participants will receive a $50 honorarium gift card for their participation. Sample collection and analyses: OGTT, ALT, AST, creatinine and lipid profile will be analyzed in Clinical Chemistry in Health Science Centre, Winnipeg. Inflammation mediators will be analyzed in the Dr. G. Shen's laboratory. Homeostatic model assessment-insulin resistance or homeostatic model assessment for insulin resistance (HOMA-IR) will be calculated based on fasting plasma glucose and insulin. Stool samples will be aliquoted and stored under -80°C before submission. Microbiome analysis will be conducted in Integrate Microbiome Resource at Dalhousie University.

Official Title
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Pilot Study on the Effects of Saskatoon Berry on Glucose Metabolism, Insulin Resistance and Gut Microbiota in Healthy Human Subjects

Conditions
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Nutritional and Metabolic Diseases

Intervention / Treatment
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* Dietary Supplement: Saskatoon berry


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects living in Winnipeg. Willingness to sign an informed consent. Exclusion Criteria: 1. History of myocardial infarction, stroke, hypertension, diabetes, hyperlipidemia, chronic kidney disease. 2) Participants are taking hypoglycemic, anti-hypertensives, lipid lowering medications or antibiotics within a 1 month.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Healthy subject (n=20) will be enrolled in a single group for oral administration of dried Saskatoon berry as snack.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>Single arm | Dietary Supplement: Saskatoon berry<br>* Freeze dried Saskatoon berry (30 g) will be orally administrated daily for 10 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose tolerance | 75 g oral glucose tolerance test (2 h postprandial plasma glucose in mM/L) | Changes from baseline to 10 weeks after the start of dietary intervention | 
| Gut microbiome | Stool will be collected for 16S rRNA gene sequencing in % of abundance | Changes from baseline to 10 weeks after the start of dietary intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipid profile | total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol in mM/L | Onset and 10 weeks after the start of dietary intervention | 
| C-reactive protein | C-reactive protein in mg/L | Onset and 10 weeks after the start of dietary intervention | 
| Liver enzymes | ALT, AST in units/L | Onset and 10 weeks after the start of dietary intervention | 
| Body mass index accord to body weight and height | Body weight in kg, heights in cm, and body mass index in kg/M^2 | Onset, 5 and 10 weeks after the start of dietary intervention | 
| Blood pressure | Systolic and diastolic blood pressure in mmHg | Onset, 5 and 10 weeks after the start of dietary intervention | 
| Tumor necrosis factor-alpha | Tumor necrosis factor-alpha in pg/mL | Onset, 5 and 10 weeks after the start of dietary intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Saskatoon berry, Glucose tolerance, Gut microbiota, Healthy subjects