Effect of Treatment With Butyric Acid in Anorexia Nervosa (AN-BUTIX)

Effetto Del Trattamento Con Acido Butirrico Sull'Anoressia Nervosa

This clinical trial aims to evaluate the therapeutic potential of oral butyric acid supplementation in individuals with anorexia nervosa (AN). T The study will assess whether butyric acid, administered alongside standard multidisciplinary care, improves weight restoration and contributes to overall clinical recovery.

The primary objectives are to determine:

- Whether butyric acid enhances weight restoration during the first 3 months of treatment.

Participants will be randomly assigned to receive either butyric acid or a placebo for 3 months, in addition to treatment-as-usual, which includes nutritional rehabilitation and cognitive-behavioral therapy.

Throughout the study, researchers will monitor:

• Changes in body weight and Body Mass Index (BMI)
• General and eating-disorder-related psychopathology
• Blood-based biomarkers related to inflammation, metabolism, and neuroendocrine function
• Gut microbiota composition and metabolites, including short-chain fatty acids

A total of 50 participants with AN are expected to be enrolled.

Study Overview

• Status: Active, not recruiting
• Conditions: Anorexia Nervosa; Gut Microbiota; Weight Trajectory
• Intervention / Treatment: Dietary supplement: Dietary Supplement: Butyric Acid; Dietary supplement: Dietary Supplement: Butyric Acid

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • FI
    • Florence, FI, Italy, 50134
      • SODc Psichiatria, Azienda Ospedaliero-Universitaria Careggi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female sex
• Age 18-65 years
• Current diagnosis of Anorexia Nervosa (DSM-5)
• Able and willing to provide informed consent
• Ability to comply with study procedures and assessments

Exclusion Criteria:

• Severe psychiatric conditions requiring inpatient hospitalization (e.g., psychosis, severe major depressive episode with suicidal intent)
• Severe medical conditions requiring inpatient care (cardiovascular, renal, hematopoietic, gastrointestinal, endocrine disorders)
• Intellectual disability, illiteracy, or conditions impairing consent or questionnaire completion
• Current participation in another experimental protocol
• Active use of probiotics
• Neutropenia (<0.5 × 10^9/L)
• Leukocytosis (>30 × 10^9/L)
• Fever > 38°C
• Radiological evidence of toxic megacolon or intestinal perforation
• Presence of colostomy
• Severe comorbidity limiting 30-day survival
• Active or past malignancy requiring chemotherapy
• Corticosteroid therapy within the past 6 months
• HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Comparator: Butyric Acid; Participants with anorexia nervosa receiving butyric acid supplementation plus Treatment As Usual.	Dietary supplement: Dietary Supplement: Butyric Acid; Daily oral supplementation with 2 capsules of microencapsulated butyric acid (Butyrose®, 550 mg each; total daily dose 1,100 mg) for 3 months, administered in addition to Treatment As Usual (nutritional rehabilitation + cognitive-behavioral therapy).; Dietary supplement: Dietary Supplement: Butyric Acid; Daily oral supplementation with 2 placebo capsules matched in appearance and composition (maltodextrins, cellulose, inert excipients), administered for 3 months in addition to Treatment As Usual.
Placebo Comparator: Placebo Comparator: Placebo; Participants with anorexia nervosa receiving placebo capsules plus Treatment As Usual.	Dietary supplement: Dietary Supplement: Butyric Acid; Daily oral supplementation with 2 capsules of microencapsulated butyric acid (Butyrose®, 550 mg each; total daily dose 1,100 mg) for 3 months, administered in addition to Treatment As Usual (nutritional rehabilitation + cognitive-behavioral therapy).; Dietary supplement: Dietary Supplement: Butyric Acid; Daily oral supplementation with 2 placebo capsules matched in appearance and composition (maltodextrins, cellulose, inert excipients), administered for 3 months in addition to Treatment As Usual.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Body weight measured in kilograms using a calibrated scale.	Baseline and 3 months
Body Mass Index (BMI)	BMI calculated as weight (kg) divided by height (m²). Unit of Measure: kg/m²	Baseline and 3 months
Gut Microbiota Composition	Assessment of the relative abundance of bacterial taxa through sequencing at baseline and 3 months. Changes over time will be evaluated to identify shifts in microbial composition and potential alterations in gut balance relevant to anorexia nervosa.	Baseline and 3 months
Short-Chain Fatty Acids (SCFAs)	Measurement of SCFA concentrations (e.g., butyrate, acetate, propionate) at baseline and 3 months. Changes in SCFA levels will be used to evaluate alterations in gut microbial metabolic activity over time.	Baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eating disorder psychopatology - Eating Disorder Examination Questionnaire 6.0 (EDE-Q 6.0; Calugi et al., 2015)	The EDE-Q measures eating-disorder psychopathology across four subscales: Restraint, Eating Concern, Shape Concern, and Weight Concern. Items are scored from 0 to 6. The Global Score is the mean of the four subscales. Higher scores indicate more severe eating-disorder symptoms. Unit of Measure: Units on a scale.	Baseline and 3 months
Eating disorder psychopathology - Eating Disorder Inventory - 3 (EDI-3; Clausen et al., 2011)	The EDI-3 evaluates psychological traits associated with eating disorders. It includes subscales such as Drive for Thinness, Bulimia, Body Dissatisfaction, Low Self-Esteem, Emotional Dysregulation, Interoceptive Deficits, Perfectionism, Asceticism, and others. Items are typically scored on 0-4 Likert scales. Higher scores indicate greater psychological dysfunction relevant to EDs. Unit of Measure: Units on a scale.	Baseline and 3 months
General psychopathology - Brief Symptom Inventory (BSI); Derogatis & Melisaratos, 1983)	The BSI assesses general psychopathology. It includes the following subscales: Somatization, Obsessive-Compulsive Symptoms, Interpersonal Sensitivity, Depression, Anxiety, Hostility, Phobic Anxiety, Paranoid Ideation, and Psychoticism. Items are rated on a 0-4 scale. Higher scores indicate greater overall psychopathology. Unit of Measure: Units on a scale.	Baseline and 3 months
Childhood maltreatment - Childhood Trauma Questionnaire - Short Form (CTQ-SF; Bernstein et al., 2003)	The CTQ-SF assesses exposure to childhood maltreatment. It includes five subscales: Emotional Abuse, Physical Abuse, Sexual Abuse, Emotional Neglect, and Physical Neglect. Subscale scores range from 5 to 25; the total score ranges from 25 to 125. Higher scores indicate more severe childhood maltreatment. Unit of Measure: Units on a scale.	Baseline
Emotional dysregulation - Difficulties in Emotion Regulation Scale (DERS; Gratz & Roemer, 2004)	The DERS measures emotion-regulation difficulties. It includes six subscales: Nonacceptance, Goals, Impulse, Awareness, Strategies, and Clarity. Total scores range from 36 to 180. Higher scores indicate greater difficulties in emotion regulation. Unit of Measure: Units on a scale	Baseline and 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory Biomarkers (pg/mL)	Blood-based inflammatory markers measured in pg/mL (e.g., IL-6, TNF-α). Higher values indicate increased inflammatory activation.	Baseline and 3 months
C-Reactive Protein (CRP)	CRP is a blood marker of systemic inflammation measured in mg/L. Higher levels indicate greater inflammatory activation.	Baseline and 3 months
Metabolic Biomarkers (mg/dL)	Metabolic markers measured in mg/dL, including glucose and lipid profile components. Variations may reflect changes in metabolic functioning and nutritional status.	Baseline and 3 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria Careggi
• Investigators: Principal Investigator: Giovanni Castellini, Medical Degree, Department of Health Sciences, University of Florence, Florence, Italy

Publications and helpful links

General Publications

• Facchin S, Vitulo N, Calgaro M, Buda A, Romualdi C, Pohl D, Perini B, Lorenzon G, Marinelli C, D'Inca R, Sturniolo GC, Savarino EV. Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease. Neurogastroenterol Motil. 2020 Oct;32(10):e13914. doi: 10.1111/nmo.13914. Epub 2020 May 31.
• Mack I, Cuntz U, Gramer C, Niedermaier S, Pohl C, Schwiertz A, Zimmermann K, Zipfel S, Enck P, Penders J. Weight gain in anorexia nervosa does not ameliorate the faecal microbiota, branched chain fatty acid profiles, and gastrointestinal complaints. Sci Rep. 2016 May 27;6:26752. doi: 10.1038/srep26752.
• 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.
• Hata T, Miyata N, Takakura S, Yoshihara K, Asano Y, Kimura-Todani T, Yamashita M, Zhang XT, Watanabe N, Mikami K, Koga Y, Sudo N. The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice. Endocrinology. 2019 Oct 1;160(10):2441-2452. doi: 10.1210/en.2019-00408.
• Castellini G, Cassioli E, Vitali F, Rossi E, Dani C, Melani G, Flaccomio D, D'Andria M, Mejia Monroy M, Galli A, Cavalieri D, Ricca V, Bartolucci GL, De Filippo C. Gut microbiota metabolites mediate the interplay between childhood maltreatment and psychopathology in patients with eating disorders. Sci Rep. 2023 Jul 20;13(1):11753. doi: 10.1038/s41598-023-38665-x.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2025
• Primary Completion (Estimated): November 12, 2026
• Study Completion (Estimated): November 12, 2028

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Actual): December 17, 2025

Study Record Updates

• Last Update Posted (Actual): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: outcome; gut microbiota; anorexia nervosa; butyric acid
• Additional Relevant MeSH Terms: Mental Disorders; Body Weight; Body Weight Changes; Feeding and Eating Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Body-Weight Trajectory; Anorexia Nervosa
• Other Study ID Numbers: 29252_spe; 29252 (Registry Identifier: Comitato Etico Area Vasta Centro - CEAVC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No