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

Official title

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

Overview

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.

Interventions

• 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 o
• 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.

Primary outcome measures

• Self-efficacy [Time frame: 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.]
• Tobacco dependence [Time frame: 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.]
• Metabolome [Time frame: 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.]
• Smoking behaviour [Time frame: From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.]

Secondary outcome measures (1)

• Psychiatric Symptoms [Time frame: From enrollment to follow-up 3 months after the end of the 6-weeks treatment period.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Austria · 3 centers

• Grüner Kreis Organization Johnsdorf Facility — Fehring
• Medical University Graz — Graz
• Sigmund Freud Private University Vienna — Vienna

Publications

• Fuchshuber J, Schober H, Wohlmuth M, Senra H, Rominger C, Schwerdtfeger A, Unterrainer HF. The effectiveness of a standardized tobacco cessation program on psychophysiological parameters in patients with addiction undergoing long-term rehabilitation: a quasi-experimental pilot study. BMC Med. 2024 May 1;22(1):184. doi: 10.1186/s12916-024-03405-z. PMID 38693570
• Peter J, Pritz A, Hiebler M, Mahmoudi M, Fuchshuber J, Morkl S, Holasek S, Humer E, Unterrainer HF. Metabolomic and gut microbial biomarkers of smoking cessation treatment in long-term drug therapy: a study protocol for a randomized controlled trial. Front Psychiatry. 2026 Mar 3;17:1677235. doi: 10.3389/fpsyt.2026.1677235. eCollection 2026. PMID 41853081

Identifiers

NCT: NCT06803706 · 1155/2024 · 1155/2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗