Human Milk Oligossaccharide and Acetate Production in Vivo

NCT04795804 | Completed DMC

• 1 other identifier: NL71611.068.19
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The study investigators hypothesize (1) that the SCFA/acetate metabolism differs between metabolic phenotypes and (2) that using a mixture of fibres that differ in degree of polymerization and branching namely a resistant starch and a human-like milk oligosaccharide enhance the acetate availability in the distal colon and systemic circulation, consequently leading to its metabolic effects. To study this, the investigators will supplement lean, normoglycaemic vs. overweight/obese, prediabetic men with the fibre mixture the day before the clinical investigation day (CID) and study during the CID its effects on fasting and postprandial substrate and energy metabolism.

Conditions

Obesity; Insulin Resistance

Outcome Measures

Primary Outcomes (15)

• Plasma acetate concentrations.

  During the clinical investigation day plasma acetate will be sampled

  plasma acetate will be sampled during the CID before the consumption of a liquid high fat mixed meal

• Plasma acetate concentrations.

  During the clinical investigation day plasma acetate will be sampled

  plasma acetate will be sampled during the CID at t=60 minutes after consumption of a liquid high fat mixed meal

• Plasma acetate concentrations.

  During the clinical investigation day plasma acetate will be sampled

  plasma acetate will be sampled during the CID at t=120 minutes after consumption of a liquid high fat mixed meal

• Plasma acetate concentrations.

  During the clinical investigation day plasma acetate will be sampled

  plasma acetate will be sampled during the CID at t=240 minutes after consumption of a liquid high fat mixed meal

• Faecal acetate concentrations.

  On the day of clinical investigation day, fecal acetate will be sampled

  Fecal acetate will be sampled in the morning before the testday

• Plasma butyrate concentrations.

  During the clinical investigation day, plasma butyrate will be sampled

  plasma butyrate will be sampled during the CID before the consumption of a liquid high fat mixed meal

• Plasma butyrate concentrations.

  During the clinical investigation day, plasma butyrate will be sampled

  plasma butyrate will be sampled during the CID at t=60 after consumption of a liquid high fat mixed meal

• Plasma butyrate concentrations.

  During the clinical investigation day, plasma butyrate will be sampled

  plasma butyrate will be sampled during the CID at t=120 after consumption of a liquid high fat mixed meal

• Plasma butyrate concentrations.

  During the clinical investigation day, plasma butyrate will be sampled

  plasma butyrate will be sampled during the CID at t=240 minutes after consumption of a liquid high fat mixed meal

• Fecal butyrate concentrations.

  On the day of clinical investigation day, fecal butyrate will be sampled

  Fecal butyrate will be sampled in the morning before the testday

• Plasma propionate concentrations.

  During the clinical investigation day, plasma propionate will be sampled

  Plasma propionate will be sampled during the CID before the consumption of a liquid high fat mixed meal

• Plasma propionate concentrations.

  During the clinical investigation day, plasma propionate will be sampled

  Plasma propionate will be sampled during the CID t=60 minutes after the consumption of a liquid high fat mixed meal

• Plasma propionate concentrations.

  During the clinical investigation day, plasma propionate will be sampled

  Plasma propionate will be sampled during the CID t=120 minutes after the consumption of a liquid high fat mixed meal

• Plasma propionate concentrations.

  During the clinical investigation day, plasma propionate will be sampled

  Plasma propionate will be sampled during the CID t=240 minutes after the consumption of a liquid high fat mixed meal

• Faecal propionate concentrations.

  On the day of clinical investigation day, fecal propionate will be sampled

  Fecal propionate will be sampled in the morning before the testday

Secondary Outcomes (6)

• Energy expenditure, fat and carbohydrate oxidation

  Indirect calorimetry will be measured before and for 4 hours after the consumption of the liquid high-fat mixed meal during the whole CID

• Breath H2 using (Bedfont EC60 Gastrolyzer, Rochester, UK).

  Breath H2 will be sampled during the CID before and at t=30, t=60, t=90, t=120 and t=240 minutes after consumption of a liquid high fat mixed meal

• Plasma glucose concentrations

  Plasma glucose concentrations will be sampled during the CID before and t=0, t=30, t=60, t=120 and t=240 minutes after consumption of a liquid high fat mixed meal

• Plasma insulin concentrations

  Plasma insulin concentrations will be sampled during the CID before and at t=0, t=30, t=60, t=120 and t=240 minutes after consumption of a liquid high fat mixed meal

• Plasma FFA concentrations

  Plasma FFA concentrations will be sampled during the CID before and at t=0, t=30, t=60, t=120 and t=240 minutes after consumption of a liquid high fat mixed meal

Study Arms (3)

Placebo

PLACEBO COMPARATOR

11.43 g (3 x 3.81 g) maltodextrin the day before the clinical investigation day

Dietary Supplement: Maltodextrin

Human milk-like oligosaccharide alone

ACTIVE COMPARATOR

12 g (3 x 4 g) of the human milk-like oligosaccharide the day before the clinical investigation day

Dietary Supplement: Human Milk Oligossaccharide

Human milk-like oligosaccharide and resistant starch

EXPERIMENTAL

12 g (3 x 4 g) of the human milk-like oligosaccharide and 7.5g resistant starch (3 x 2.5 g) the day before the clinical investigation day

Dietary Supplement: Human Milk Oligossaccharide and resistant starch

Interventions

Human Milk Oligossaccharide DIETARY_SUPPLEMENT

The day before the CIDs, the participants receive the supplements 3x a day in randomized order

Human milk-like oligosaccharide alone

Maltodextrin DIETARY_SUPPLEMENT

The day before the CIDs, the participants receive the supplements 3x a day in randomized order

Placebo

Human Milk Oligossaccharide and resistant starch DIETARY_SUPPLEMENT

The day before the CIDs, the participants receive the supplements 3x a day in randomized order

Human milk-like oligosaccharide and resistant starch

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Lean (BMI ≥ 20kg/m2 and ≤ 24.9kg/m2) healthy men aged 30 - 65 years
• as well as
• overweight/obese (BMI ≥ 25kg/m2 and ≤ 34.9kg/m2) prediabetic men aged between 30 - 65 years

You may not qualify if:

• Type 2 diabetes mellitus (defined as fasting plasma glucose ≥ 7.1 mmol/L and 2h glucose ≥ 11.1 mmol/L)
• Gastroenterological diseases or abdominal surgery;
• Cardiovascular diseases, cancer, liver or kidney malfunction, disease with a life expectancy shorter than 5 years;
• Abuse of products; alcohol and drugs, excessive nicotine use defined as \>20 cigarettes per day;
• Plans to lose weight or following of a hypocaloric diet;
• Regular supplementation of pre- or probiotic products, use of pre- or probiotics 3 months prior to the start of the study;
• Intensive exercise training more than three hours a week;
• Use of any medication that influences glucose or fat metabolism and inflammation (i.e. NSAIDs);
• Regular use of laxation products;
• Use of antibiotics in the last three months (antibiotics use can alter substantially the gut microbiota composition).
• Follow a vegan diet.

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University

Maastricht, Limburg, 5229ER, Netherlands

Location

Related Publications (1)

• Canfora EE, Vliex LMM, Wang T, Nauta A, Bouwman FG, Holst JJ, Venema K, Zoetendal EG, Blaak EE. 2'-fucosyllactose alone or combined with resistant starch increases circulating short-chain fatty acids in lean men and men with prediabetes and obesity. Front Nutr. 2023 Jul 17;10:1200645. doi: 10.3389/fnut.2023.1200645. eCollection 2023.

  PMID: 37529001 DERIVED

MeSH Terms

Conditions

Obesity; Insulin Resistance

Interventions

maltodextrin; Resistant Starch

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Fiber; Dietary Carbohydrates; Carbohydrates; Polysaccharides; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: March 12, 2021
• Study Start: February 4, 2020
• Primary Completion: October 15, 2021
• Study Completion: October 15, 2021
• Last Updated: November 3, 2021

Record last verified: 2021-03

Locations

NL (1)