Effects of Butyrate on Affective Processes

Study Overview
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Brief Summary
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The effects of butyrate on psychobiological processes are examined in a sample of healthy volunteers.

Detailed Description
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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.

Official Title
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Effects of Butyrate on Affective Processes

Conditions
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Stress, Emotions, Fear

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Butyrate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo (cellulose) | Dietary Supplement: Placebo<br>* Cellulose<br>|
| Active Comparator: Butyrate<br>Sodium butyrate | Dietary Supplement: Butyrate<br>* Sodium butyrate<br>|

What is the study measuring?
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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 |