Rectal Short Chain Fatty Acids Combinations and Substrate and Energy Metabolism

NCT01983046 | Completed DMC

• 1 other identifier: NL44507.068
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Gut microbiota is being increasingly recognized as an important factor in fat distribution, insulin sensitivity and glucose and lipid metabolism. Accordingly, the intestinal microbiota could play an important role in the development of obesity and type 2 diabetes mellitus. The role of gut-derived short-chain fatty acids (SCFA), the formation of which is enhanced by microbial fermentation of fiber, is still controversial. One study found that an increase in the formation of SCFA stimulated energy extraction from diet, with subsequent weight gain. In contrast, supplementation of non-fermentable carbohydrates, which lead to an increase in SCFA formation, had beneficial effects on body weight control and insulin sensitivity. Of note, a study showed that butyrate supplementation in mice prevented diet-induced obesity and insulin resistance. At the present time, our understanding of the effects of SCFA on human metabolism (in gut or systemically) is still limited. Yet, in light of the health claims of certain dietary fibers (prebiotics), a detailed picture of the physiology of human SCFA metabolism and its interaction with the microbiome is of pivotal importance. We hypothesize that the differential availability of SCFA impacts human metabolism differently. To determine whether rectal administration of SCFA is a good model for studying the metabolic effects of SCFA we first have performed a pilot study (METC 11-3-079). In this pilot study we have determined if rectal administration of sodium acetate has the same effects on substrate and energy metabolism compared to proximal administration. Our results indicate that the primary outcome parameter fat oxidation was significantly changed during post-absorptive conditions, when sodium acetate in a concentration of 180mM was administered in the distal part of the colon. In contrast, no effect on energy expenditure or substrate oxidation was seen when sodium acetate was administered in the proximal colon. Consequently, the distal part of the colon seems to be a good model to determine effects of gut-derived SCFA on the human substrate and energy metabolism. Therefore, we will administer in this study the SCFA rectally by using enemas. We will administer different combinations of SCFA to healthy, overweight male volunteers and examine effects on metabolism. This study is an important part of a Gastrointestinal Health TIFN project (GH003 WP 1.2), which will provide more insight in how increased availability of a beneficial SCFA mixture might serve as a basis for rational nutritional strategies in the prevention and treatment of obesity and type 2 diabetes mellitus. To obtain rational nutritional strategies, a next step in this TIFN project will be focusing on dietary ingredients modulating intestinal microbiota and subsequent SCFA production.

Conditions

Obesity; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• fat oxidation

  we will measure fat oxidation and energy expenditure by using the ventilated hood system

  4 hours total (2 hours fasting, 2 hours postprandial)

Secondary Outcomes (3)

• Hormones that influence energy metabolism

  4 hours total (2 hours fasting and 2 hours postprandial)

• Circulating metabolites

  4 hours total (2 hours fasting and 2 hours postprandial)

• Hormones that influence energy metabolism - Circulating metabolites - Inflammatory markers - plasma SCFA content; - Indirect markers of insulin sensitivity - Appetite (VAS-scoring).

  4 hours total (2 hours fasting and 2 hours postprandial)

Study Arms (4)

placebo

PLACEBO COMPARATOR

placebo

Drug: Three different mixture of acetate, butyrate and propionate and palcebo

high acetate ratio

ACTIVE COMPARATOR

high acetate ratio

Drug: Three different mixture of acetate, butyrate and propionate and palcebo

high butyrate ratio

ACTIVE COMPARATOR

high butyrate ratio

Drug: Three different mixture of acetate, butyrate and propionate and palcebo

high propionate ratio

ACTIVE COMPARATOR

high propionate ratio

Drug: Three different mixture of acetate, butyrate and propionate and palcebo

Interventions

Three different mixture of acetate, butyrate and propionate and palcebo DRUG

high acetate ratio; high butyrate ratio; high propionate ratio; placebo

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Overweight
• Obese men

You may not qualify if:

• Athletes
• Diabetes mellitus

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Top Institute Food and Nutrition: collaborator

Study Sites (1)

University Maastricht

Maastricht, Limburg, 6229 ER, Netherlands

Location

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2

Interventions

Butyrates; Propionates

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Design

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

Study Record Dates

• First Submitted: September 17, 2013
• First Posted: November 13, 2013
• Study Start: September 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: October 21, 2014

Record last verified: 2014-10

Locations

NL (1)