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Saskatoon Berry on Metabolism and Gut Microbiota in Healthy Subjects

Not Applicable
Conditions
Nutritional and Metabolic Diseases
Interventions
Dietary Supplement: Saskatoon berry
Registration Number
NCT04809688
Lead Sponsor
University of Manitoba
Brief Summary

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 (SB) powder attenuated hyperglycemia, hyperlipidemia, insulin resistance, inflammation, liver steatosis and gut dysbiosis in diet-induced insulin resistant mice, a model for T2D. The results in anti-diabetic activities of SB powder have been supported by other groups in high fat fed rats. Our preliminary studies in 20 healthy subjects demonstrated that dried whole SB (40 g/day for 10 weeks) significantly reduced fasting plasma glucose, total and LDL-cholesterol, systolic blood pressure, and increased plasma glucagon-like peptide compared to baseline, which was associated with increased intake of total fiber and decreased intake of saturated fat. The changes in metabolic and vascular variables significantly correlated with the alterations in gut microbiota. The combination of findings suggest that Saskatoon berry is good candidate of prebiotic functional food as a supplemental remedy for reducing the risk for metabolic syndrome and preventing or managing T2D. The effect of Saskatoon berry and its products on metabolic disorders have not been studied in healthy human subjects. We propose to examine the effects of oral administration of freeze-dried whole SB on glucose metabolism, insulin resistance and gut microbiota in healthy subjects in a single arm, open labeled phase I clinical trial.

Detailed Description

Subject recruitment: Healthy subjects and prediabetes (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, glucagon-like peptide-1 (GLP-1), liver enzymes (alanine transaminase or ALT, aspartate transaminase or AST), creatinine, lipid profile and inflammation markers (high-sensitive C-reactive protein or hs-CRP) will be measured as baseline. Stool samples will be collected in stool DNA preservation and collection kit.

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 blood withdrawal for biochemical tests and OGTT as the same as visit 2. 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. Insulin, hs-CRP and GLP-1 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. Fecal short chain fatty acids (SCFA) will be measured in Microbiome Insight in University of British Columbia.

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
20
Inclusion Criteria
  1. Healthy subjects living in Winnipeg.
  2. Willingness to sign an informed consent.
Exclusion Criteria
  1. History of myocardial infarction, stroke, hypertension, diabetes, hyperlipidemia, chronic kidney disease.
  1. Participants are taking hypoglycemic, anti-hypertensives, lipid lowering medications or antibiotics within a 1 month.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Single armSaskatoon berrySingle arm
Primary Outcome Measures
NameTimeMethod
Fasting plasma glucoseChanges from baseline to 10 weeks after the start of dietary intervention

Fasting plasma glucose in mM/L

Total serum cholesterolChanges from baseline to 10 weeks after the start of dietary intervention

Fasting total cholesterol in mM/L

Secondary Outcome Measures
NameTimeMethod
Lipid profile beside total cholesterolOnset and 10 weeks after the start of dietary intervention

Triglycerides, LDL-cholesterol, HDL-cholesterol and non-HDL-cholesterol in mM/L

C-reactive proteinOnset and 10 weeks after the start of dietary intervention

C-reactive protein in mg/L

Liver enzymesOnset and 10 weeks after the start of dietary intervention

ALT, AST in units/L

Body mass index accord to body weight and heightOnset, 5 and 10 weeks after the start of dietary intervention

Body weight in kg, heights in cm, and body mass index in kg/M\^2

Blood pressureOnset, 5 and 10 weeks after the start of dietary intervention

Systolic and diastolic blood pressure in mmHg

Gut micrbiotaBaseline and 10 weeks of SB intake

16S-rRNA sequencing of stool samples

Glucagaon-like peptideBetween baseline and 10 weeks of SB intake

Plasma levels analyzed using ELISA

Insulin and homeostasis model assessment of insulin resistance (HOMA-IR)Between baseline and 10 weeks of SB intake

Fasting plasma insulin analyzed using ELISA and HOMA-IR estimated via simultaneous plasma glucose and insulin

Trial Locations

Locations (1)

University of Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

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