The Role of Short Chain Fatty Acids in Microbiota-gut-brain Axis

Stress Clinical Trial

— SCFA-AP  

Official title:

Effects of Short Chain Fatty Acids on Affective Processes in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03688854
• Other study ID #: S60501
• Status: Completed
• Phase: N/A
• Start date: January 4, 2018
• Est. completion date: September 15, 2018

Study information

• Verified date: October 2018
• Source: KU Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The role of short chain fatty acids (SCFA) in the microbiota-gut-brain axis is examined in a sample of healthy volunteers. SCFA are the major products of bacterial fermentation of dietary fiber in the colon, and are hypothesised to mediate the bidrectional communication between the gut and the residing microbiota on the one hand, and the central nervous system on the other hand. We perform a 1-week intervention with SCFA and measure their effects on a range of affective outcomes in healthy male volunteers.

Description:

The study is an interventional double-blind, placebo-controlled, parallel group design with 3 arms (placebo, high-dose of SCFA, and low-dose of SCFA). The high and low doses of SCFA are equivalent to 20 and 10 grams of fiber respectively. Healthy male participants follow a low-fiber diet for the study duration (11 days). On day 4, baseline measurements are taken in the lab, including biological samples and psychophysiological measurements. Participants then consume placebo or SCFA for one week and revisit the lab on day 11 for a second measurement of the outcomes of interest. Specifically, we investigate the effect of SCFA supplementation on affective processing, including stress sensitivity, fear-related processes (e.g. extinction learning), and attentional bias to emotional stimuli. Volunteers also respond to questionnaires in relation to mood, and provide biological samples (blood and faecal samples) for analysis of circulating short chain fatty acids and microbiota composition, respectively.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: September 15, 2018
• Est. primary completion date: September 15, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• Male participants

• Age range 20-40 years

• BMI range 18.5-27

• Dutch as native-language

Exclusion Criteria:

• previous or current neurological, psychiatric, gastrointestinal or endocrine disorders, or other relevant medical history

• current or recent regular medication use

• previous or current substance/alcohol dependence or abuse (> 2 units per day/14 units per week)

• one or more diagnoses based on the mini-international neuropsychiatric interview

• smoking

• night-shift work

• adherence to vegan or vegetarian diets

• use of pre- or probiotics within one month preceding the study

• use of antibiotics within 3 months preceding the study

• previous experience with one of the tasks used in the study

Related Conditions & MeSH terms

• Emotions
• Fear
• Stress

Intervention

Dietary Supplement:
• SCFA mixture
Intracolonic administration

Locations

Country	Name	City	State
Belgium	UZ Leuven/Stresslab	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
KU Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stress sensitivity	Induction of cognitive, physical, and social stress using Maastricht Acute Stress Test. Stress hormone cortisol is quantified.	1 year
Secondary	Stress sensitivity (subjective)	Induction of cognitive, physical, and social stress using Maastricht Acute Stress Test. Participant rate how much stress, discomfort, and pain they feel on a 10-cm visual analogue scale, with higher values indicating greater stress, discomfort, and pain. This is done prior to stress induction, in the middle, and at the end.	1 year
Secondary	Cortisol awakening response	Measuring chronic stress by quantifying cortisol in morning samples (5 samples taken form the moment of waking every 15 minutes for 1 hour)	1 year
Secondary	Fear	Exploring fear-related processes (conditioning, extinction, recall, and renewal) by means of a computerised task. Fear response is measured using skin conductance.	1 year
Secondary	Fear (subjective)	Exploring fear-related processes (conditioning, extinction, recall, and renewal) by means of a computerised task. Fear response is measured subjective reports.	1 year
Secondary	Attentional bias to emotional stimuli	Use of a dot-probe task to task attentional bias and change in attentional bias following SCFA vs. placebo supplementation. This is done via a computerised task, where reaction times are quantified.	1 year
Secondary	Perceived Stress Scale (PSS)	The Perceived Stress Scale (PSS) was devised by Cohen et al. (1983). It is a 14-item instrument designed to measure the degree to which situations in one's life are appraised as stressful. It provides a tool for examining issues about the role of appraised stress levels in the aetiology of disease and behavioural disorders. The scale is designed such that it asks the respondent to rate the frequency of his/her feelings and thoughts related to events and situations that occurred over a selected time-frame. Notably, high PSS scores have been correlated with higher biomarkers of stress, such as cortisol.	1 year
Secondary	Positive and Negative Affect Schedule (PANAS)	The PANAS consists of two 10-item mood scales and was developed to provide brief measures of negative affect (NA) and positive affect (PA). NA and PA reflect dispositional dimensions, with high-NA epitomized by subjective distress and unpleasurable engagement, and low-NA by the absence of these feelings. By contrast, PA represents the extent to which an individual experiences pleasurable engagement with the environment. Respondents are asked to rate the extent to which they have experienced each particular emotion within a specified time period, on a 5-point scale. The scale points are: 1 'very slightly or not at all', 2 'a little', 3 'moderately', 4 'quite a bit', and 5 'very much'.	1 year
Secondary	Depression, Anxiety, and Stress Scale (DASS-21)	The DASS is a set of three self-report scales designed to measure the negative emotional states of depression, anxiety and stress. Each of the three DASS scales contains 14 items, divided into subscales of 2-5 items with similar content. The Depression scale assesses dysphoria, hopelessness, devaluation of life, self-deprecation, lack of interest/involvement, anhedonia, and inertia. The Anxiety scale assesses autonomic arousal, skeletal muscle effects, situational anxiety, and subjective experience of anxious affect. The Stress scale is sensitive to levels of chronic non-specific arousal. Subjects are asked to use 4-point severity/frequency scales to rate the extent to which they have experienced each state over the past week. Scores for Depression, Anxiety and Stress are calculated by summing the scores for the relevant items. DASS21 will be used in the present study.	1 year
Secondary	Gastointestinal symptom rating scale (GSRS)	The GSRS (Svellund et al., 1988) is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhoea and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. The reliability and validity of the GSRS are well-documented, and norm values for a general population are available.	1 year
Secondary	Microbiota composition	Analysis of microbiota composition at baseline and after SCFA mixture administration in faecal samples	1 year
Secondary	Circulating SCFA	Measurement of SCFA concentration in blood samples	1 year