Clinical trial NCT06064201: The Role of Short-chain Fatty Acids in Malnutrition on Stress, Eating Behavior, and Nutritional State
Official title: The Role of Short-chain Fatty Acids (SCFAs) in Regulating Stress Responses, Eating Behavior, and Nutritional State in Anorexia Nervosa: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Anorexia Nervosa
Keywords: anorexia nervosa
short-chain fatty acids
gut-brain axis
microbiota
stress response
eating behavior
gut microbiome
food choice
Trier Social Stress Test
randomized controlled trial
Lead sponsor: KU Leuven
Sponsor class: OTHER
First posted: 2023-10-03
Enrollment: 92
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Salivary cortisol response following TSST
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Restrictive food choices during Food Choice Task
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Nutritional status (BMI)
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following the start of the intervention)
Secondary outcomes:
measure: Neuroendocrine Measures (salivary alpha amylase)
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Neuroendocrine Measures (ACTH)
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Subjective stress in relation to TSST
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Subjective stress appraisal in relation to TSST
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Subjective anxiety in relation to TSST
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Subjective hunger in relation to TSST
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Subjective appetite in relation to TSST
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Heart rate response to acute laboratory stress
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Heart rate variability to acute laboratory stress
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Electrodermal activity to acute laboratory stress
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Self controlled choices during Food Choice Task
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Eating Disorder Symptoms
timeFrame: Self-reported questionnaires are completed at the baseline visit (at hospital admission and before intervention), three weeks into the intervention, post intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following
measure: Restrained, emotional and external eating behaviour
timeFrame: Self-reported questionnaires are completed at the baseline visit (at hospital admission and before intervention), three weeks into the intervention, post intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following
measure: Hedonic hunger
timeFrame: Self-reported questionnaires are completed at the baseline visit (at hospital admission and before intervention), three weeks into the intervention, post intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following
Other outcomes:
measure: Short-chain fatty acid levels
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Fecal gut microbiota profile
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following the start of the intervention)
measure: Gastrointestinal Symptoms
timeFrame: Self-reported questionnaires are completed at the baseline visit (at hospital admission and before intervention), three weeks into the intervention, post intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following
measure: Physical movement
timeFrame: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
measure: Depressive symptoms
timeFrame: Self-reported questionnaires are completed at the baseline visit (at hospital admission and before intervention), three weeks into the intervention, post intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following
measure: Positive and negative affect
timeFrame: Self-reported questionnaires are completed at the baseline visit (at hospital admission and before intervention), three weeks into the intervention, post intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following
measure: Percieved stress
timeFrame: Self-reported questionnaires are completed at the baseline visit (at hospital admission and before intervention), three weeks into the intervention, post intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following
Locations:
city: Leuven
country: Belgium
facility: UZ/KU Leuven
state: Vlaams Brabant
Study officials:
References: