Metabolome and Gut Microbiome Changes During Smoking Cessation in Long-term Drug Therapy in a Therapeutic Community

May 15, 2026 updated by: Sigmund Freud PrivatUniversitat

Metabolomic and Gut Microbial Biomarkers of Smoking Cessation Treatment in Long-term Drug Therapy: A Randomized Controlled Trial

Theoretical Framework: Cigarette smoking is the leading preventable cause of death worldwide, with nicotine dependence notably common among individuals with Substance Use Disorders (SUD). Smoking exacerbates both physical and mental health issues, further complicating the treatment of SUD. Current therapeutic approaches for SUD often prove inadequate, indicating a need for new strategies. Recent advancements in metabolomics and gut microbiome research have provided valuable insights into the biological mechanisms underlying addiction.

Objectives: This study aims to investigate the therapeutic potential of smoking cessation for individuals with SUD, using a six-week intervention within a therapeutic community. The research specifically explores the psychobehavioral, metabolic, and gut microbiome domains. It is hypothesized that smoking cessation will improve emotional regulation, self-efficacy, and reduce substance craving, mediated by changes in metabolic and microbiome profiles linked to brain reward systems.

Methods: A randomized controlled trial (N=150) will be conducted, examining outcomes such as clinical relapse rates, microbial and metabolic markers, particularly in choline and folate metabolism. Participants with SUD (n=100) will undergo a six-week smoking cessation intervention, with pre- and post-assessments, compared to a control group receiving treatment as usual. Metabolomic and microbiome analyses will be conducted using blood and stool samples, alongside psychological assessments via questionnaires. Assessments on a behavioural level will take place at a 3-months follow-up.

A cross-sectional, non-interventional healthy control group (n=50) will be examined at a single timepoint with an anologous panel of psychological variables, blood and stool to ascertain differences between smokers with SUD and healthy controls.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Austria
      • Fehring, Austria, 8350
        • Recruiting
        • Grüner Kreis Organization Johnsdorf Facility
        • Contact:
      • Graz, Austria, 8036
        • Recruiting
        • Medical University Graz
        • Contact:
      • Vienna, Austria, 1020

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • diagnosis of a form of substance use disorder (F1x.x) by a licensed psychiatrist according to ICD-10
  • minimum age of 18 years
  • sufficient knowledge of the German language
  • willingness to quit smoking
  • willingness and ability to consent

Inclusion criteria for healthy controls :

  • minimum age of 18 years
  • sufficient knowledge of the German language
  • willingness and ability to consent

Exclusion Criteria:

  • lack of consent, inability to provide informed consent
  • age below 18,
  • acute psychotic symptoms or acute suicidal tendencies
  • cardiovascular disease
  • pregnancy or breastfeeding
  • severe mental or organic illnesses (such as epilepsy, brain tumors, recent major surgery), tumor diseases, dementia (Mini Mental Score <20), severe autoimmune diseases or immunosuppression, acute infections, or acute diarrhea, prior gastrointestinal surgery (except appendectomy)
  • probiotic intake within the last 6 months,
  • ongoing consumtion of dietary supplements, probiotics, antibiotics, or prebiotic supplements during the study
  • prior participation in a smoking cessation programme

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Treatment As Usual
Patients in the TAU group receive long-term rehabilitation drug treatment according to the 'community as a treatment'-model
Behavioral: Long-term drug therapy within a therapeutic community
The standard treatment within the 'Grüner Kreis' therapeutic community - which all participants will receive - consists of group therapy (once a week), individual psychotherapy (once a week), counselling by social workers, psychiatric consultations, as well as sport-, art- and work-therapy. Daily life is organized according to principles of therapeutic community-based addiction treatment.
Experimental: 6-weeks smoking cessation cognitive-behavioral therapy intervention
The "smoke free in 6 weeks" program is a standardized behavioural therapy intervention that takes place once a week for 1.5 hours over 6 weeks and is provided by the Austrian health insurance provider Österreichische Gesundheitskasse (ÖGK).
Behavioral: Long-term drug therapy within a therapeutic community
The standard treatment within the 'Grüner Kreis' therapeutic community - which all participants will receive - consists of group therapy (once a week), individual psychotherapy (once a week), counselling by social workers, psychiatric consultations, as well as sport-, art- and work-therapy. Daily life is organized according to principles of therapeutic community-based addiction treatment.
Behavioral: 6-weeks CBT smoking cessation programme
Held in the therapeutic community, the intervention will employ principles of cognitive-behavioural therapy (CBT) coupled with personalized recommendations for nicotine replacement. The Austrian Health Insurance standard for therapy will be guiding the program's content, which is tailored for inpatient clients. Specifically, the following interventions based on CBT techniques will be applied in the weekly group sessions consisting of 10 to 15 participants: Psychoeducation including information on tobacco addiction, health risks, advice on relapse prevention and the handling of craving, motivation building, behavioural observation.
No Intervention: Healthy controls
Control group with n=50 healthy adult subjects, examined at a single timepoint. No interventions will be administered in this arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Self-efficacy
Time Frame: From enrollment to follow-up 3 months after the end of the 6-weeks treatment period
Self-efficacy as a psychological variable and will be assessed by the Self-Efficacy Scale (SWE), a self-report instrument for measuring general optimistic self-confidence. It consists of 10 items and measures optimistic competence expectancy, i.e., confidence in solving difficult situations with one's own abilities.
From enrollment to follow-up 3 months after the end of the 6-weeks treatment period
General substance-related craving
Time Frame: From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.
Substance related craving will be assessed by the MaCS (Mannheim Craving Scale). consists of 12 items and four additional items and is rated on a 5- point Likert scale.
From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.
Tobacco dependence
Time Frame: From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.
Tobacco dependence will be assessed by The Fagerström Test for Cigarette Dependence (formerly Fagerström Test for Nicotine Dependence; FTND). It consists of 6 categorically scaled items that assess the number of smoked cigarettes per day (CPD), compulsive use, and dependence intensity.
From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.
Primary Affects
Time Frame: From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.
Primary Affects, as proposed by Jaak Panksepp will be assessed by the German Version of the Brief Affective Neuroscience Personality Scales including a LUST Scale (BANPS-GL), a self-report questionnaire.
From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.
Metabolome
Time Frame: From enrollment to the end of the 6-weeks treatment period.
Metabolome will be ascertained from blood via state-of-the-art NMR (nuclear magnetic resonance).
From enrollment to the end of the 6-weeks treatment period.
Gut microbiome
Time Frame: From enrollment to the end of the 6-weeks treatment period.
Gut microbiome will be ascertained via 16s-rRNA sequencing from stool.
From enrollment to the end of the 6-weeks treatment period.
Smoking behaviour
Time Frame: From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.
Participants will be asked regarding their daily smoked cigarettes in the last two weeks (interval scaled). A second single item question will be, if participants have been completely abstinent from tobacco smoking in the last two weeks (dichotome).
From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Psychiatric Symptoms
Time Frame: From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.
For the evaluation of psychopathology, the ICD-10 Symptom Rating (ISR) questionnaire will be utilized. In accordance with the ICD-10, this self-assessment questionnaire, comprising 30 items, is designed to comprehensively assess the status and severity of mental disturbances. Symptoms of the six symptomatic patterns - depressive, anxiety, obsessive-compulsive, eating disorders, somatoform syndrome, and post-traumatic stress disorder - are assessed.
From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sigmund Freud PrivatUniversitat

Collaborators

Medical University of Graz

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 5, 2025

Primary Completion (Estimated)

October 28, 2026

Study Completion (Estimated)

October 28, 2026

Study Registration Dates

First Submitted

January 23, 2025

First Submitted That Met QC Criteria

January 27, 2025

First Posted (Actual)

January 31, 2025

Study Record Updates

Last Update Posted (Actual)

May 18, 2026

Last Update Submitted That Met QC Criteria

May 15, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1155/2024 (Other Identifier: Ethikkommission der Medizinischen Universität Graz)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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