Rectal Short Chain Fatty Acids Combinations and Substrate and Energy Metabolism

Obesity Clinical Trial

Official title:

The Effects of Rectal Administration of SCFA on Human Substrate and Energy Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01983046
• Other study ID #: NL44507.068
• Status: Completed
• Phase: N/A
• First received: September 17, 2013
• Last updated: October 20, 2014
• Start date: September 2013
• Est. completion date: February 2014

Study information

• Verified date: October 2014
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 50 Years

Eligibility

Inclusion Criteria:

• Overweight

• Obese men

Exclusion Criteria:

• Athletes

• Diabetes mellitus

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Obesity
• Type 2 Diabetes

Intervention

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

Locations

Country	Name	City	State
Netherlands	University Maastricht	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Top Institute Food and Nutrition

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Hormones that influence energy metabolism		4 hours total (2 hours fasting and 2 hours postprandial)	No
Secondary	Circulating metabolites		4 hours total (2 hours fasting and 2 hours postprandial)	No
Secondary	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)	No