Effects of Rifaximin on Gut Microbiota and Emotion

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05587036
• Other study ID #: S66407
• Secondary ID: 2021-006814-35
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: February 2, 2023
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Lukas Van Oudenhove, MD, PhD
• Phone: +32 16 33 01 47
• Email: lukas.vanoudenhove[@]kuleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fear
• Healthy Volunteers
• Stress

Intervention

Drug:
• Rifaximin
Rifaximin oral tablet, 550 mg, twice daily, two-weeks

Dietary Supplement:
• Placebo
Placebo oral tablet, twice daily, two-weeks

Locations

Country	Name	City	State
Belgium	UZ/KU Leuven	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Fecal gut microbiota profile	Assessing gut microbiota profile before and after intervention	Throughout study completion, on average 1 year
Other	Serum short-chain fatty acid levels	Quantification of serum SCFA (µM) before and after intervention	Throughout study completion, on average 1 year
Other	Cytokine levels	Quantification of inflammatory cytokines (pg/ml) before and after intervention	Throughout study completion, on average 1 year
Other	C-reactive protein levels	Quantification of C-reactive protein levels (ng/ml) before and after intervention	Throughout study completion, on average 1 year
Other	Heart rate variability	Assessing heart rate variability (ms) with ECG before and after intervention	Throughout study completion, on average 1 year
Other	Heart rate	Assessing heartbeat (bpm) with a blood pressure monitor before and after intervention	Throughout study completion, on average 1 year
Other	Blood pressure	Assessing blood pressure (systolic/diastolic mmHg) with a blood pressure monitor before and after intervention	Throughout study completion, on average 1 year
Other	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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