Effects of Butyrate on Affective Processes

The effects of butyrate on psychobiological processes are examined in a sample of healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Stress; Emotions; Fear
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Butyrate

Detailed Description

The study is an interventional triple-blind, placebo-controlled, parallel group design with 2 arms (placebo, butyrate). Healthy male participants adhere to a low-fiber diet for the duration of the study (11 days). At the baseline study visit, measurements are taken in the lab, including biological samples and psychophysiological measurements. Participants then consume placebo or butyrate for 1 week and revisit the lab on day 11 for a second measurement of the outcomes of interest. Specifically, we investigate the effect of colonic butyrate administration on affective processing, including stress sensitivity and fear-related processes (e.g. extinction learning). Volunteers also respond to questionnaires in relation to mood and GI symptoms, and provide biological samples (saliva, blood, and faecal samples) for analysis of cortisol levels, circulating short chain fatty acids and serum BDNF, and faecal SCFA, respectively.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • I Am Not In The U.S. Or Canada
    • Leuven, I Am Not In The U.S. Or Canada, Belgium, 3000
      • UZ Leuven/Stresslab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male participants
• Age range 20-40 years
• BMI range 18.5-25
• Dutch or English 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (cellulose)	Dietary supplement: Placebo; Cellulose
Active Comparator: Butyrate; Sodium butyrate	Dietary supplement: Butyrate; Sodium butyrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stress sensitivity (cortisol)	Induction of cognitive, physical, and social stress using Maastricht Acute Stress Test. Stress hormone cortisol is quantified by gathering multiple saliva samples throughout the stress induction and recovery during both pre-intervention and post-intervention visit.	through study completion, on average 1 year and 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 at both pre- and post-intervention visits.	through study completion, on average 1 year and 5 months
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) on the morning of the pre- and post-intervention visits.	through study completion, on average 1 year and 5 months
Fear	Exploring fear-related processes (conditioning, extinction, recall, and renewal) by means of a computerised task. Fear response is measured using skin conductance, and a skin conductance response is calculated.	through study completion, on average 1 year and 5 months
Fear (subjective)	Exploring fear-related processes (conditioning, extinction, recall, and renewal) by means of a computerised task. Fear response is measured subjectively by asking participants to indicate their expectancy of an aversive stimulus.	through study completion, on average 1 year and 5 months
Positive and Negative Affect Schedule (PANAS)	Assessing ratings on the subscales of PANAS, positive and negative affect. PA subscale scores range between 10-50, with higher scores indicating better outcome. NA subscale scores range between 10-50, with higher scores indicating worse outcome.	through study completion, on average 1 year and 5 months
Perceived Stress Scale (PSS)	Assessing ratings on PSS. Scores range between 0-40 with higher scores indicating worse outcome.	through study completion, on average 1 year and 5 months
Depression, anxiety, and stress scales (DASS-21)	Assessing ratings on the subscales of DASS-21, depression, anxiety, and stress subscales. Higher scores on these subscales indicates a worse outcome. Normal (depression: 0 - 4; anxiety: 0 - 3; stress: 0 - 7), Mild (depression: 5 - 6; axiety: 4 - 5; stress: 8 - 9), Moderate (depression: 7 - 10; anxiety: 6 - 7; stress: 10 - 12), Severe (depression: 11 - 13; anxiety: 8 - 9; stress: 13 - 16), Extremely Severe (depression: 14 +; anxiety: 10 +; stress: 17 +).	through study completion, on average 1 year and 5 months
Leiden Index of Depression Sensitivity-Revised (LEIDS-R)	Assessing ratings on the subscales of LEIDS-R and its total score. This is a self-report on cognitive reactivity comprised of 34 items with six subscales. Hopelessness/suicidality; Acceptance/Coping; Aggression; Control/Perfectionism; Risk Aversion; Rumination.	through study completion, on average 1 year and 5 months
Gastrointestinal symptom rating scale (GSRS)	Assessing ratings on the subscales of GSRS and its total score. It has 5 subscales (Reflux, Diarrhea, Constipation, Abdominal Pain, and Indigestion Syndrome). Subscale scores range from 1 to 7 and higher scores indicates a worse outcome.	through study completion, on average 1 year and 5 months
Serum SCFA	Quantification of serum SCFA (μM) at pre- and post-intervention	through study completion, on average 1 year and 5 months
Faecal SCFA	Quantification of faecal SCFA in samples provided at pre- and post-intervention	through study completion, on average 1 year and 5 months
Serum BDNF	Quantification of fasting serum BDNF levels (µg/mL)	through study completion, on average 1 year and 5 months

Collaborators and Investigators

• Sponsor: KU Leuven
• Investigators: Principal Investigator: Kristin Verbeke, Prof, kristin.verbeke@kuleuven.be

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2021
• Primary Completion (Actual): December 11, 2022
• Study Completion (Actual): December 11, 2022

Study Registration Dates

• First Submitted: January 21, 2021
• First Submitted That Met QC Criteria: January 21, 2021
• First Posted (Actual): January 25, 2021

Study Record Updates

• Last Update Posted (Estimate): January 4, 2023
• Last Update Submitted That Met QC Criteria: January 3, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: S60501- Exp 2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No