The Role of Short Chain Fatty Acids in Microbiota-gut-brain Axis (SCFA-AP)

• ClinicalTrials.gov Identifier: NCT03688854
• Recruitment Status: Completed
• First Posted: September 28, 2018
• Last Update Posted: October 2, 2018
• Sponsor: KU Leuven
• Information provided by (Responsible Party): Kristin Verbeke, KU Leuven

Tracking Information

• First Submitted Date: September 23, 2018
• First Posted Date: September 28, 2018
• Last Update Posted Date: October 2, 2018
• Actual Study Start Date: January 4, 2018
• Actual Primary Completion Date: September 15, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 26, 2018)

Stress sensitivity [ Time Frame: 1 year ]

Induction of cognitive, physical, and social stress using Maastricht Acute Stress Test. Stress hormone cortisol is quantified.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 26, 2018)

• Stress sensitivity (subjective) [ Time Frame: 1 year ]
  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.
• Cortisol awakening response [ Time Frame: 1 year ]
  Measuring chronic stress by quantifying cortisol in morning samples (5 samples taken form the moment of waking every 15 minutes for 1 hour)
• Fear [ Time Frame: 1 year ]
  Exploring fear-related processes (conditioning, extinction, recall, and renewal) by means of a computerised task. Fear response is measured using skin conductance.
• Fear (subjective) [ Time Frame: 1 year ]
  Exploring fear-related processes (conditioning, extinction, recall, and renewal) by means of a computerised task. Fear response is measured subjective reports.
• Attentional bias to emotional stimuli [ Time Frame: 1 year ]
  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.
• Perceived Stress Scale (PSS) [ Time Frame: 1 year ]
  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.
• Positive and Negative Affect Schedule (PANAS) [ Time Frame: 1 year ]
  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'.
• Depression, Anxiety, and Stress Scale (DASS-21) [ Time Frame: 1 year ]
  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.
• Gastointestinal symptom rating scale (GSRS) [ Time Frame: 1 year ]
  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.
• Microbiota composition [ Time Frame: 1 year ]
  Analysis of microbiota composition at baseline and after SCFA mixture administration in faecal samples
• Circulating SCFA [ Time Frame: 1 year ]
  Measurement of SCFA concentration in blood samples

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Role of Short Chain Fatty Acids in Microbiota-gut-brain Axis
• Official Title: Effects of Short Chain Fatty Acids on Affective Processes in Humans
• Brief 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.
• Detailed 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Basic Science

Condition

• Emotions
• Stress
• Fear

Intervention

Dietary Supplement: SCFA mixture

Intracolonic administration

Study Arms

• Placebo Comparator: Placebo
  Placebo are capsules containing cellulose.
  Intervention: Dietary Supplement: SCFA mixture
• Experimental: SCFA mixture low dose
  Encapsulated SCFA mixture in the ratio of 67:6:27 (acetate, propionate, butyrate) equivalent of 10 grams of fiber.
  Intervention: Dietary Supplement: SCFA mixture
• Experimental: SCFA mixture high dose
  Encapsulated SCFA mixture in the ratio of 67:6:27 (acetate, propionate, butyrate) equivalent of 20 grams of fiber.
  Intervention: Dietary Supplement: SCFA mixture

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 26, 2018): 66
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: September 15, 2018
• Actual Primary Completion Date: September 15, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 20 Years to 40 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT03688854
• Other Study ID Numbers: S60501
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Kristin Verbeke, KU Leuven
• Study Sponsor: KU Leuven
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kristin Verbeke, Prof; KU Leuven

• PRS Account: KU Leuven
• Verification Date: October 2018