Effects of Rifaximin on Gut Microbiota and Emotion

A Randomized, Triple-blind, Placebo-controlled Study on the Effect of Rifaximin on Psychobiological Functions in Healthy Men

A randomized, triple-blind, placebo-controlled study on the effect of rifaximin on psychobiological functions in healthy men.

Study Overview

• Status: Recruiting
• Conditions: Stress; Healthy Volunteers; Fear
• Intervention / Treatment: Drug: Rifaximin; Dietary supplement: Placebo

Detailed Description

This study is a randomized, triple-blind, placebo-controlled, interventional trial aiming to elucidate the impact of rifaximin-induced gut microbiota alteration to the psychobiological functioning of healthy men. The intervention will be performed in a parallel group design where one group will receive rifaximin (Targaxan 550 mg) twice daily for two weeks (treatment arm), while the other group will receive placebo (placebo arm).

Primary objective: to test the effect of rifaximin on stress sensitivity and fear-related processes

Secondary objective: to determine the mediating and/or moderating factors that underlie rifaximin-induced psychobiological changes

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Lukas Van Oudenhove, MD, PhD; Phone Number: +32 16 33 01 47; Email: lukas.vanoudenhove@kuleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ/KU Leuven
    • Contact: Lukas Van Oudenhove, MD, PhD; Phone Number: +32 16 33 01 47; Email: lukas.vanoudenhove@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. Proficiency in English and/or Dutch
3. Healthy with no intestinal and/or psychological complaints
4. Access to a -18°C freezer (i.e. ordinary household freezer)
5. Male participants
6. Age 18-50 years
7. BMI 18.5-25 kg/m2

Exclusion Criteria:

1. Participant has a history of previous or current neurological, psychiatric, gastrointestinal or endocrine disorder
2. Any disorder, which in the Investigator's opinion might jeopardize the participant's safety or compliance with the protocol
3. Any prior or concomitant treatment(s) that might jeopardize the participant's safety or that would compromise the integrity of the Trial
4. Participation in an interventional Trial with an investigational medicinal product (IMP) or device
5. Hypersensitivity to the active substance rifaximin, to any rifamycin (e.g. rifampicin or rifabutin) or any of the excipients
6. Current or recent medication use
7. Use of antibiotics within three months preceding the study
8. Current or recent (1-month) infection (e.g. common cold, influenza, COVID-19, etc.)
9. Previous or current substance/alcohol dependence or abuse (>2 units per day or 14 units per week)
10. One or more diagnoses based on the mini international neuropsychiatric interview (MINI-S)
11. One or more diagnoses based on ROME IV for gastrointestinal disorders
12. Smoking
13. Night-shift work
14. Adherence to special diets (e.g. vegan, vegetarian, weight-loss, lactose-free, gluten-free, etc.)
15. Use of pre- or probiotics within one month preceding the study
16. Previous experience with any of the tasks used in the study (not including questionnaires)
17. Color vision deficiency (colorblindness)
18. Magnetic Resonance Imaging (MRI) contraindications, including claustrophobia, severe back problems, conditions that would interfere with MRI scanning (e.g. cochlear implant, metal fragments in eyes, metallic body inclusion, or other metal implanted in the body), and if the participant does not want to be informed of incidental findings that might be found during imaging.

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
Experimental: Rifaximin; Rifaximin oral tablets, 550 mg, twice daily, two-weeks	Drug: Rifaximin; Rifaximin oral tablet, 550 mg, twice daily, two-weeks; Other Names: Targaxan
Placebo Comparator: Placebo; Placebo oral tablets, twice daily, two-weeks	Dietary supplement: Placebo; Placebo oral tablet, twice daily, two-weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stress sensitivity (biological)	Biological stress sensitivity is measured by quantifying cortisol levels (ng/ml) from multiple saliva samples taken before, during, and after a stress task performed during the pre-intervention and post-intervention visit.	Throughout study completion, on average 1 year
Stress sensitivity (psychological)	Psychological stress sensitivity is measured through subjective stress reports of the participants using the visual analogue scale (VAS). VAS scorings are taken before, during, and after a stress task performed during the pre-intervention and post-intervention visit.	Throughout study completion, on average 1 year
Fear (biological)	Fear-related processes will be explored using a computerized task. Biological fear response is measured using skin conductance, and a skin conductance response (μS) is calculated .	Throughout study completion, on average 1 year
Fear (psychological)	Fear-related processes will be explored using a computerized task. Psychological fear response is measured subjectively by asking participants to indicate their expectancy score of an aversive stimulus.	Throughout study completion, on average 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive and Negative Affect Schedule (PANAS)	Assessing ratings on the subscales of PANAS, positive and negative affect, before and after intervention. 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.	Throughout study completion, on average 1 year
Perceived Stress Scale (PSS)	Assessing ratings on PSS before and after intervention. PSS scores range between 0-40 with higher scores indicating worse outcome.	Throughout study completion, on average 1 year
Gastrointestinal Symptom Rating Scale (GSRS)	Assessing ratings on the subscales of GSRS and its total score before and after intervention. 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.	Throughout study completion, on average 1 year
Leiden Index of Depression Sensitivity (LEIDS-R)	Assessing ratings on the subscales of LEIDS-R and its total score before and after intervention. 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.	Throughout study completion, on average 1 year
State-Trait Anxiety Inventory, State Anxiety Subscale (STAI-S)	Assessing ratings on the momentary (state) anxiety subscale of STAI before and after intervention. This is a self-report comprised of 20 questions specifically for state anxiety, rated on a 4-point scale. State anxiety is rated with anxiety absent and anxiety present questions. Anxiety absent questions constitute the absence of anxiety in a statement like, "I feel secure." Anxiety present questions represent the presence of anxiety in a statement like "I feel worried." The 4-point scale are as follows: 1 'not at all', 2 'somewhat', 3 'moderately so', and 4 'very much so'.	Throughout study completion, on average 1 year
Brain response to stress	Brain response (brain oxygenation level-dependent signals) to a fMRI-adapted stress task will be measured before and after intervention	Throughout study completion, on average 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal gut microbiota profile	Assessing gut microbiota profile before and after intervention	Throughout study completion, on average 1 year
Serum short-chain fatty acid levels	Quantification of serum SCFA (μM) before and after intervention	Throughout study completion, on average 1 year
Cytokine levels	Quantification of inflammatory cytokines (pg/ml) before and after intervention	Throughout study completion, on average 1 year
C-reactive protein levels	Quantification of C-reactive protein levels (ng/ml) before and after intervention	Throughout study completion, on average 1 year
Heart rate variability	Assessing heart rate variability (ms) with ECG before and after intervention	Throughout study completion, on average 1 year
Heart rate	Assessing heartbeat (bpm) with a blood pressure monitor before and after intervention	Throughout study completion, on average 1 year
Blood pressure	Assessing blood pressure (systolic/diastolic mmHg) with a blood pressure monitor before and after intervention	Throughout study completion, on average 1 year
Brain metabolite concentration	Relative quantification of brain metabolites (mmol/L) using 1H-Magnetic Resonance Spectroscopy before and after intervention	Throughout study completion, on average 1 year

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Lukas Van Oudenhove, MD, PhD, KU Leuven; Principal Investigator: Kristin Verbeke, Pharm, PhD, KU Leuven; Principal Investigator: Boushra Dalile, PhD, KU Leuven; Principal Investigator: Jeroen Raes, PhD, VIB-KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: September 29, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 19, 2022

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Stress; Fear; Rifaximin; Anti-Bacterial Agents; Short-Chain Fatty Acid; Microbiota-Gut-Brain Axis
• Additional Relevant MeSH Terms: Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: S66407; 2021-006814-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD that underlie results in a publication will be made available to other researchers with all identifying information removed.
• IPD Sharing Time Frame: The data will become available upon publication with no time limitations.
• IPD Sharing Access Criteria: The data will be publicly available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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