Clinical trial NCT06920641: Effects of Tagatose on Glycemic Response and Gastrointestinal Microbiota in Healthy Adults
Official title: Effects of Tagatose on Glycemic Response and Gastrointestinal Microbiota: A Randomized, Placebo-Controlled, Double-Blind, Crossover Trial in Healthy Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Glucose Intolerance
Microbial Colonization
Keywords: tagatose
prebiotic
fecal microbiota
glucose
insulin
gut health
glycemic control
Lead sponsor: PepsiCo Global R&D
Sponsor class: INDUSTRY
First posted: 2025-04-10
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in incremental area under the plasma glucose curve (ignoring area below the baseline, iAUC) over each 4-week intervention period
timeFrame: 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
Secondary outcomes:
measure: Fecal microbiota composition
timeFrame: Pre-dose baseline and Week 4 for each of two 4-week dosing periods
Other outcomes:
measure: Fasting serum short-chain fatty acid (SCFA)
timeFrame: Pre-dose baseline Day 1 and Day 29 of each of two 4-week dosing periods
measure: Fasting serum bile acids (BA)
timeFrame: Pre-dose baseline Day 1 and Day 29 of each of two 4-week dosing periods
measure: Serum glucose total AUC 0-2 hours, peak concentrations and peak rises for glucose; glucose concentrations and increments at each time point over 2 hours
timeFrame: Fasted at -5 minutes Time 0 pre-dose, post-dose 15, 30, 45, 60, 90 and 120 minutes post-dose.
measure: Serum insulin iAUC 0-2 hours; total AUC 0-2 hours, peak concentrations and peak rises for insulin; insulin concentrations and increments at each time point over 2h
timeFrame: Fasted at -5 minutes, Time 0 pre-dose, post-dose 15, 30, 45, 60, 90 and 120 minutes post-dose.
measure: Indices of insulin resistance
timeFrame: Pre-dose baseline Day 1 and Day 29 of each of two 4-week dosing periods
measure: Indices of insulin secretion
timeFrame: Pre-dose baseline Day 1 and Day 29 of each of two 4-week dosing periods
measure: Matsuda's index of insulin sensitivity
timeFrame: Pre-dose baseline Day 1 and Day 29 of each of two 4-week dosing periods
measure: Abdul-Ghani et al. indices of liver insulin sensitivity
timeFrame: Pre-dose baseline Day 1 and Day 29 of each of two 4-week dosing periods, from 0-30 minutes after the oral glucose load for plasma glucose and serum insulin
measure: Abdul-Ghani et al. indices of muscle insulin sensitivity
timeFrame: Pre-dose baseline Day 1 and Day 29 of each of two 4-week dosing periods, from 0-120 minutes
measure: Intake of dietary fiber and selected macro- and micro-nutrients
timeFrame: Recorded consumption for 2 weekdays and 1 weekend day during the week before the visit at the end of each 28 day dosing period
measure: Optional Outcome: Glucagon-like peptide-1 (GLP-1) concentrations pending significant changes in butyrate concentrations
timeFrame: Pre-dose baseline Day 1 and Day 29 of each of two 4-week dosing periods
Locations:
city: Toronto
country: Canada
facility: INQUIS Clinical Research
state: Ontario
Study officials:
affiliation: INQUIS Clinical Research
name: Thomas MS Wolever, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: