Glucose Intolerance, Microbial Colonization
Conditions
Keywords
tagatose, prebiotic, fecal microbiota, glucose, insulin, gut health, glycemic control
Brief summary
The primary objective of this clinical-trial is to determine, in subjects with impaired fasting glucose (IFG) and/or insulin resistance (IR), if tagatose meets the definition of a prebiotic, namely that consuming tagatose for 4 weeks selectively stimulates the selective growth of bacteria in the colon and is associated with a health benefit (oral glucose tolerance) when compared to consuming the control treatment (10g sucrose) for 4 weeks.
Detailed description
Available evidence suggests that tagatose may act as a prebiotic compound. It has been hypothesized that undigested tagatose reaches the colon and is fermented by colonic bacteria, resulting in the production of short-chain fatty acids (SCFA) which stimulate GLP-1 secretion from colonic L-cells, which, in turn, improves glycemic control by increasing insulin sensitivity and insulin secretion. However, the fermentation of tagatose and subsequent effects have only been demonstrated in preclinical models, with limited clinical trials examining the effect of tagatose on glycemic control. Given the dearth of clinical evidence in humans supporting the ability of tagatose to be fermented in the colon and to improve glycemic control, the present study aims to explore if tagatose is selectively utilized by human gut microorganisms conferring a beneficial effect on glycemic control. Thus, the investigators aim to recruit 55 healthy adults with impaired fasting glucose and/or hyperinsulinemia into a double-blind, randomized, controlled, clinical trial with a cross-over design.
Interventions
OTHERTagatose
Sachet containing 10g tagatose to be dissolved in 250ml water and taken once daily on Days 1-28 of a 4-week dosing period. (1 of 2 dosing periods separated by a 4-week washout)
OTHERPlacebo
Sachet containing 10g sucrose to be dissolved in 250ml water and taken once daily on Days 1-28 of a 4-week dosing period. (1 of 2 dosing periods separated by a 4-week washout)
Sponsors
PepsiCo Global R&D
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy individuals aged 18-50 years, inclusive * BMI 20.0 to 34.9 kg/m², inclusive * Fasting serum glucose \<7.0 mmol/L * Fasting serum glucose between 6.1 and 6.9 mmol/L (110 to 124 mg/dL), inclusive and/or fasting insulin \>50th percentile (\>43 pmol/L = \>7.2 μU/mL) * No history of diabetes mellitus * Systolic blood pressure \<160 mmHg and diastolic blood pressure \<100 mmHg * Agree not to change current dietary habits with the exception of the following: agreement to avoid foods/drinks with added probiotics, prebiotics, and/or postbiotics, fermented foods (e.g., yogurt, sauerkraut, kombucha), and dietary supplements containing fiber, probiotics, prebiotics, synbiotics, and/or postbiotics for at least 2 weeks before Week 0 (Day 1) and throughout the duration of their participation in the study * Modified TAPS (tobacco, alcohol, prescription medications and other substances) tool responses are within allowable usage limits * Ability to understand the study procedures and willing to provide informed consent to participate in the study * Subjects must be eligible to receive income in Canada and be covered by a health insurance plan such as OHIP * Subjects are willing to sign the informed consent prior to any procedures conducted
Exclusion criteria
* Failure to meet any one of the inclusion criteria * Reported history of metabolic (including type 1 and type 2 diabetes mellitus), hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, psychiatric disorders, or any other medical conditions that, in the judgment of the Principal Investigator, increase the risk to the subject or others or may affect results. * Antibiotic use within 60 days before randomization * Hospital admission for major trauma, or major medical or surgical event, as judged by the Principal Investigator, within 6 months of screening. * Use of medications such as, but not limited to, hypoglycemic agents, GLP-I agonists, systemic steroids, antipsychotics, or any others that increase the risk to the subject or others or may affect results, as judged by the Principal Investigator. * Current diagnosis or history of irritable bowel syndrome (IBS), inflammatory bowel disease (IBD, including ulcerative colitis and Crohn's disease), functional constipation (defined by the Rome IV diagnostic criteria 1-8, diarrhea (loose or watery stools for the last 3 months without abdominal pain or bothersome bloating in more than 25% of stools), celiac disease, lactose intolerance and/or malabsorption, gastroparesis, gastroenteritis, endometriosis, diverticulosis, gastric or duodenal ulcers, pancreatitis, or eating disorder; history of intestinal surgery (excluding appendectomy or herniorrhaphy), or history of bariatric surgery. * Extreme dietary habits, including but not limited to intentional consumption of an extremely high fiber diet (e.g., \>50g per day), gluten-free, low-carb, vegan, ketogenic, low FODMAP. * Consumption of \>2 sugar sweetened or artificially sweetened beverages (soda and juice) on average per day (note: not including sweetened tea/coffee) * Known intolerance, sensitivity, or allergy to any ingredients in the study test products * Self-reported pregnancy or breastfeeding or planning to become pregnant. * Participation in any clinical trial within the past 30 days or any PepsiCo protocol within the past 6 months. * Subjects who, in the opinion of the investigator, are unable or unlikely to comply with the dosing schedule and study evaluations.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in incremental area under the plasma glucose curve (ignoring area below the baseline, iAUC) over each 4-week intervention period | Before (-5 minutes and 0 minutes) and 15, 30, 45, 60, 90 and 120 minutes after overnight fasted subjects start to consume 50 grams of glucose on Day 1 and Day 29 of each of two 4-week intervention periods | Finger stick blood samples obtained fasted prior to consuming 50 grams of glucose. Six additional finger stick blood samples obtained over the next 2 hours beginning 15 minutes after consumption. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fecal microbiota composition | Pre-dose baseline and Week 4 for each of two 4-week dosing periods | Stool sample measured via 16S rRNA sequencing |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORThomas MS Wolever, MD, PhD
INQUIS Clinical Research
Outcome results
None listed