Clinical trial NCT04809688: Saskatoon Berry on Metabolism and Gut Microbiota in Healthy Subjects
Official title: Effects of Saskatoon Berry on Glucose Metabolism, Insulin Resistance and Gut Microbiota in Healthy Human Subjects
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Nutritional and Metabolic Diseases
Keywords: Saskatoon berry
Glucose tolerance
Gut microbiota
Healthy subjects
Lead sponsor: University of Manitoba
Sponsor class: OTHER
Collaborators: name: Health Sciences Centre Foundation, Manitoba
First posted: 2021-03-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Healthy subject (n=20) will be enrolled in a single group for oral administration of dried Saskatoon berry as snack.

Healthy subjects (n=10) will be enrolled in a single group for assessing glycemic index for dried Saskatoon berry.

Prediabetes (n=20) will be randomized in two groups for dried Saskatoon berry and placebo.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

2) Participants are taking hypoglycemic, anti-hypertensives, lipid lowering medications or antibiotics within a 1 month.

Primary outcomes:
measure: Fasting plasma glucose
timeFrame: Changes from baseline to 10 weeks after the start of dietary intervention
measure: Total serum cholesterol
timeFrame: Changes from baseline to 10 weeks after the start of dietary intervention
Secondary outcomes:
measure: Lipid profile beside total cholesterol
timeFrame: Onset and 10 weeks after the start of dietary intervention
measure: C-reactive protein
timeFrame: Onset and 10 weeks after the start of dietary intervention
measure: Liver enzymes
timeFrame: Onset and 10 weeks after the start of dietary intervention
measure: Body mass index accord to body weight and height
timeFrame: Onset, 5 and 10 weeks after the start of dietary intervention
measure: Blood pressure
timeFrame: Onset, 5 and 10 weeks after the start of dietary intervention
measure: Gut micrbiota
timeFrame: Baseline and 10 weeks of SB intake
measure: Glucagaon-like peptide
timeFrame: Between baseline and 10 weeks of SB intake
measure: Insulin and homeostasis model assessment of insulin resistance (HOMA-IR)
timeFrame: Between baseline and 10 weeks of SB intake
Other outcomes:
measure: Dietary intake, physical activities
timeFrame: Onset and 10 weeks after the start of dietary intervention
Locations:
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
Study officials:
affiliation: University of Manitoba
name: Garry Shen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhao R, Khafipour E, Sepehri S, Huang F, Beta T, Shen GX. Impact of Saskatoon berry powder on insulin resistance and relationship with intestinal microbiota in high fat-high sucrose diet-induced obese mice. J Nutr Biochem. 2019 Jul;69:130-138. doi: 10.1016/j.jnutbio.2019.03.023. Epub 2019 Apr 9.
citation: Huang F, Zhao R, Xia M, Shen GX. Impact of Cyanidin-3-Glucoside on Gut Microbiota and Relationship with Metabolism and Inflammation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice. Microorganisms. 2020 Aug 14;8(8):1238. doi: 10.3390/microorganisms8081238.
citation: du Preez R, Wanyonyi S, Mouatt P, Panchal SK, Brown L. Saskatoon Berry Amelanchier alnifolia Regulates Glucose Metabolism and Improves Cardiovascular and Liver Signs of Diet-Induced Metabolic Syndrome in Rats. Nutrients. 2020 Mar 27;12(4):931. doi: 10.3390/nu12040931.