Effects of Rifaximin on Gut Microbiota and Emotion

Sponsor
Universitaire Ziekenhuizen KU Leuven (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05587036
Collaborator
(none)
60
1
2
12
5

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Participants, investigators, and personnel involved in data analyses are blinded to the intervention. Unblinding occurs after all data has been collected and analysed.
Primary Purpose:
Basic Science
Official Title:
A Randomized, Triple-blind, Placebo-controlled Study on the Effect of Rifaximin on Psychobiological Functions in Healthy Men
Anticipated Study Start Date :
Nov 1, 2022
Anticipated Primary Completion Date :
Nov 1, 2023
Anticipated Study Completion Date :
Nov 1, 2023

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Stress sensitivity (biological) [Throughout study completion, on average 1 year]

      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.

    2. Stress sensitivity (psychological) [Throughout study completion, on average 1 year]

      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.

    3. Fear (biological) [Throughout study completion, on average 1 year]

      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 .

    4. Fear (psychological) [Throughout study completion, on average 1 year]

      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.

    Secondary Outcome Measures

    1. Positive and Negative Affect Schedule (PANAS) [Throughout study completion, on average 1 year]

      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.

    2. Perceived Stress Scale (PSS) [Throughout study completion, on average 1 year]

      Assessing ratings on PSS before and after intervention. PSS scores range between 0-40 with higher scores indicating worse outcome.

    3. Gastrointestinal Symptom Rating Scale (GSRS) [Throughout study completion, on average 1 year]

      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.

    4. Leiden Index of Depression Sensitivity (LEIDS-R) [Throughout study completion, on average 1 year]

      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.

    5. State-Trait Anxiety Inventory, State Anxiety Subscale (STAI-S) [Throughout study completion, on average 1 year]

      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'.

    6. Brain response to stress [Throughout study completion, on average 1 year]

      Brain response (brain oxygenation level-dependent signals) to a fMRI-adapted stress task will be measured before and after intervention

    Other Outcome Measures

    1. Fecal gut microbiota profile [Throughout study completion, on average 1 year]

      Assessing gut microbiota profile before and after intervention

    2. Serum short-chain fatty acid levels [Throughout study completion, on average 1 year]

      Quantification of serum SCFA (μM) before and after intervention

    3. Cytokine levels [Throughout study completion, on average 1 year]

      Quantification of inflammatory cytokines (pg/ml) before and after intervention

    4. C-reactive protein levels [Throughout study completion, on average 1 year]

      Quantification of C-reactive protein levels (ng/ml) before and after intervention

    5. Heart rate variability [Throughout study completion, on average 1 year]

      Assessing heart rate variability (ms) with ECG before and after intervention

    6. Heart rate [Throughout study completion, on average 1 year]

      Assessing heartbeat (bpm) with a blood pressure monitor before and after intervention

    7. Blood pressure [Throughout study completion, on average 1 year]

      Assessing blood pressure (systolic/diastolic mmHg) with a blood pressure monitor before and after intervention

    8. Brain metabolite concentration [Throughout study completion, on average 1 year]

      Relative quantification of brain metabolites (mmol/L) using 1H-Magnetic Resonance Spectroscopy before and after intervention

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UZ/KU Leuven Leuven Belgium 3000

    Sponsors and Collaborators

    • 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 Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Lukas Van Oudenhove, Principal Investigator, Universitaire Ziekenhuizen KU Leuven
    ClinicalTrials.gov Identifier:
    NCT05587036
    Other Study ID Numbers:
    • S66407
    • 2021-006814-35
    First Posted:
    Oct 19, 2022
    Last Update Posted:
    Oct 19, 2022
    Last Verified:
    Oct 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Lukas Van Oudenhove, Principal Investigator, Universitaire Ziekenhuizen KU Leuven
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 19, 2022