The Role of Short-chain Fatty Acids in Malnutrition on Stress, Eating Behavior, and Nutritional State

NCT ID: NCT06064201

Last Updated: 2023-10-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-30
• Study Completion Date: 2025-11-30

Brief Summary

This clinical trial aims to test the psychobiological effects of certain substances produced by gut bacteria, known as short-chain fatty acids (SCFAs), in people with anorexia nervosa.

Detailed Description

Objective This protocol proposes investigating the effects of short-chain fatty acids (SCFAs), produced by gut bacterial fermentation of dietary fiber, as mediators of microbiota-gut-brain interactions on the acute stress response, eating behavior, and nutritional state in malnourished patients with anorexia nervosa (AN). SCFAs have recently been proposed as crucial mediators of the microbiome's effects on the host. Emerging evidence suggests that SCFAs impact human physiology through various physiological pathways and may regulate stress responses and eating behavior.

Method The investigators will conduct a randomized, triple-blind, placebo-controlled trial in 92 AN patients. Patients will receive either a placebo or a mixture of SCFAs (acetate propionate, butyrate) using colon-delivery capsules (CDCs) for six weeks. This clinical trial is an add-on to the standard inpatient psychotherapeutic program focusing on nutritional rehabilitation.

Hypotheses The investigators hypothesize that colonic SCFAs delivery will modulate neuroendocrine, cardiovascular, and subjective responses to an acute laboratory psychosocial stress task. As secondary outcome measures, the investigators will assess alterations in restrictive eating behavior and nutritional status, as reflected by changes in body mass index (BMI). Additionally, the investigators will explore changes in microbiota composition, gastrointestinal symptoms, eating disorder psychopathology, and related comorbidities.

Discussion The findings of this study can enhance our understanding of how gut microbiota-produced metabolites, particularly SCFAs, impact the stress response and eating behavior of individuals with AN. It has the potential to provide essential insights into the complex interplay between the gut, stress system, and eating behavior and facilitate new therapeutic targets for stress-related psychiatric disorders.

Conditions

Anorexia Nervosa

Study Design

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

Study Groups

Short-chain fatty acids (SCFAs)

SCFAs will be delivered directly to the colon using pH-dependent colon delivery capsules (CDCs).

Group Type: EXPERIMENTAL

Short-chain fatty acids (SCFAs)

Intervention Type: OTHER

The SCFAs mixture contains acetate, butyrate, and propionate in a ratio of 60:20:20, and the total daily amount of SCFAs is equivalent to the fermentation of 10g of arabinoxylan oligosaccharides. Participants will be asked to consume these capsules spread at four intervals throughout the day. The nursing staff will distribute the capsules to the participants individually, supervise their intake, and monitor adherence by capsule count.

Microcrystalline cellulose

Placebo capsules

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

To serve as a placebo, microcrystalline cellulose will be included in the same type of CDCs.

Interventions

Short-chain fatty acids (SCFAs)

The SCFAs mixture contains acetate, butyrate, and propionate in a ratio of 60:20:20, and the total daily amount of SCFAs is equivalent to the fermentation of 10g of arabinoxylan oligosaccharides. Participants will be asked to consume these capsules spread at four intervals throughout the day. The nursing staff will distribute the capsules to the participants individually, supervise their intake, and monitor adherence by capsule count.

Intervention Type: OTHER

Placebo

To serve as a placebo, microcrystalline cellulose will be included in the same type of CDCs.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Participants are female.
• Participants are at least 16 years of age.
• Participants are Dutch-speaking.
• Participants meet the diagnostic criteria of anorexia nervosa based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013). The first time the participant met these criteria was less than seven years ago.
• Participants have a current BMI < 17,5 (kg/m2).
• Participants are on the waiting list for a psychiatric/psychotherapeutic inpatient treatment program with nutritional rehabilitation on the eating disorder ward of the University Psychiatric Hospital Leuven.
• Participants can access a -18°C home freezer for stool storage.

Exclusion Criteria

• Any medical or psychiatric disorder, which in the Investigator's opinion, might jeopardize the participant's safety or compliance with the protocol.
• Any prior or concomitant treatment(s) that might jeopardize the participant's safety or that would compromise the integrity of the Trial.
• Substance/alcohol/illegal drug abuse or dependence or evidence for chronic uses of sedatives, drugs and/or sleep medication.
• High caffeine intake (> 1000 ml coffee daily or equivalent quantities of other caffeine-containing substances).
• Use of pre- or probiotics within the last month before the start of the study.
• Use of antibiotics within the last three months before the start of the study.
• Pregnancy or intention to become pregnant.
• Previous experience with one of the tasks used in the study.
• Use of antipsychotics
• Use of selective serotonin reuptake inhibitors (SSRIs), oral contraceptives, or other drugs is allowed if patients are on a stable dosage for at least four weeks.

• Minimum Eligible Age: 16 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Elske Vrieze

Professor dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UZ/KU Leuven

Leuven, Vlaams Brabant, Belgium

Countries

Belgium

Central Contacts

Elske Vrieze, MD PhD

Role: CONTACT

elske.vrieze@upckuleuven.be

+32 16 34 81 46

Facility Contacts

Elske Vrieze, MD PhD

Role: primary

elske.vrieze@upckuleuven.be

+32 16 34 81 46

References

Quagebeur R, Dalile B, Raes J, Van Oudenhove L, Verbeke K, Vrieze E. The role of short-chain fatty acids (SCFAs) in regulating stress responses, eating behavior, and nutritional state in anorexia nervosa: protocol for a randomized controlled trial. J Eat Disord. 2023 Oct 26;11(1):191. doi: 10.1186/s40337-023-00917-6.

Reference Type: DERIVED

PMID: 37884972 (View on PubMed)

Other Identifiers

S66404

Identifier Type: -

Identifier Source: org_study_id