Brain Responses to Short-Chain Fatty Acid Intervention

NCT ID: NCT06546683

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2026-12-31

Brief Summary

A randomized, triple-blind, placebo-controlled study on the effect of colon-delivered short-chain fatty acids (SCFAs) on neural responses to stress and neuroepigenetics.

Detailed Description

The goal of this interventional study is to study the underlying mechanism of the attenuating effect of colon-delivered SCFAs on the cortisol response to stress. Pre-clinical studies suggest that the histone-deacetylase (HDAC)-inhibiting properties of SCFAs are the main mechanism underlying SCFA-induced changes in stress, cognition and behavior.

Primary objective: to test the effect of colon-delivered SCFA intervention versus placebo on HDAC expression in the brain and neural responses to stress

Secondary objective: to determine the effects of colon-delivered SCFA administration versus placebo on inflammatory and autonomic responses to stress and to determine the mediating and/or moderating factors that potentially underlie SCFA-induced changes to stress responses (HDAC expression in stress-responsive regions, serum SCFA levels)

To this end, 32 participants will be asked to undergo a pre- and post-intervention visit, separated by one week intervention with either colon-delivered SCFAs or placebo (16 per group). During the study visits, participants undergo simultaneous PET-MR imaging with [11C]Martinostat. They undergo the Montreal Imaging Stress Test (MIST) and the Maastricht Acute Stress Test (MAST) at each visit.

Conditions

Stress; Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Short-Chain Fatty Acids

SCFAs will be delivered directly to the colon using pH-dependent colon delivery capsules

Group Type: EXPERIMENTAL

Short-Chain Fatty Acids

Intervention Type: OTHER

Colon-delivery capsules of Short-Chain Fatty Acids will be administered in a ratio of 60:20:20, thus 150 mmol of acetate, 50 mmol of propionate and 50 mmol of butyrate equivalent to 20g of fibers, once daily, one week

Placebo

Colon-delivery capsules of microcrystalline cellulose

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Microcrystalline Cellulose will be used as placebo, one daily, one week

Interventions

Short-Chain Fatty Acids

Colon-delivery capsules of Short-Chain Fatty Acids will be administered in a ratio of 60:20:20, thus 150 mmol of acetate, 50 mmol of propionate and 50 mmol of butyrate equivalent to 20g of fibers, once daily, one week

Intervention Type: OTHER

Placebo

Microcrystalline Cellulose will be used as placebo, one daily, one week

Intervention Type: OTHER

Eligibility Criteria

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. Access to a -18°C freezer (i.e. ordinary household freezer)

4. Male participants

5. Age 18-45 years

6. 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 jeopardise the participant's safety or compliance with the protocol (as assessed by medical staff on the research team)

3. Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the study

4. Participation in an interventional Trial with an investigational medicinal product (IMP) or device

5. Current or recent (3-month) medication use (especially antibiotics, cardiovascular drugs, steroids, non-steroid anti-inflammatory drugs, centrally effective drugs)

6. Current or recent (1-month) infection (e.g. common cold, influenza, COVID-19, etc.)

7. Recent (1-month) vaccination (e.g. flu shot, SARS-COV-2 vaccine, etc)

8. Smoking

9. Night-shift work

10. Adherence to special diets (e.g. vegan, vegetarian, weight-loss, lactose-free, gluten- free, etc.)

11. Use of pre- or probiotics within one month preceding the study

12. Previous experience with any of the tasks used in the study (not including questionnaires)

13. Neuroimaging contraindications

14. If the participant invokes that he does not want to be informed of eventual pathology that might be found during imaging (invokes the "right not to know")

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Lukas Van Oudenhove

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lukas Van Oudenhove, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

KU Leuven

Annalena Fuchs, MSc

Role: STUDY_DIRECTOR

KU Leuven

Kristin Verbeke, Pharm, PhD

Role: PRINCIPAL_INVESTIGATOR

KU Leuven

Boushra Dalile, PhD

Role: PRINCIPAL_INVESTIGATOR

KU Leuven

Locations

UZ/KU Leuven

Leuven, , Belgium

Countries

Belgium

Central Contacts

Lukas Van Oudenhove, MD, PhD

Role: CONTACT

lukas.vanoudenhove@kuleuven.be

+32 16 33 01 47

Facility Contacts

Lukas Van Oudenhove, MD, PhD

Role: primary

Other Identifiers

S68154

Identifier Type: -

Identifier Source: org_study_id