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NCT Number: NCT07586150

Personalized Pharmaco-Lifestyle Interventions for Severe Mental Illnesses (LIFETRAIN)

This randomized, rater-blind, multicenter clinical trial will evaluate whether a personalized pharmaco-lifestyle intervention improves mental functioning in adults with severe mental illness, including schizophrenia, bipolar disorder, or major depressive disorder. Participants will be randomized to either a modular individualized intervention program or a structured psychoeducation control condition. The individualized intervention may include physical exercise, an anti-inflammatory diet, sleep intervention, social prescribing, semaglutide for eligible participants with overweight or obesity, and optional closed-loop transcranial alternating current stimulation for participants with prominent depressive symptoms. The primary outcome is change in the SF-36 Mental Component Summary score from baseline to Month 3.

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Key information

Conditions

Severe Mental Illness Behavior Behavioral Symptoms Bipolar Disorder Bipolar Disorder (BD) Bipolar and Related Disorders Depression Depression / Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders Schizophrenia Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Medical University of Vienna, Vienna, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18 to 65 years
  • Able and willing to provide written informed consent
  • Diagnosis of schizophrenia, bipolar disorder, or major depressive disorder according to DSM-5-TR, confirmed by M.I.N.I.
  • Female participants of childbearing potential must agree to use an effective method of contraception
  • Stable psychopathology defined as BPRS less than or equal to 41, MADRS less than or equal to 34, and YMRS less than or equal to 25, with stable psychopharmacological treatment for at least 2 weeks
  • Reduced functioning at screening defined as SF-36 score less than or equal to 40
  • If using benzodiazepines, dose less than or equal to 2 mg lorazepam equivalent per day
  • Stable somatic condition for at least 4 weeks
  • For semaglutide treatment: overweight with BMI at least 27 and less than 30 kg/m² plus at least one weight-related risk condition, or obesity with BMI at least 30 kg/m²
  • For optional adaptive neurostimulation: MADRS score at least 19
  • Expected ability to comply with study procedures in the investigator's judgment

Exclusion criteria

  • Unable to provide informed consent
  • Current or past neurological disorder or structural brain pathology that may affect study procedures
  • Known intolerance or hypersensitivity to semaglutide
  • Pregnancy or lactation
  • Serious suicidal risk
  • Substance dependence within the last 3 months
  • BMI less than 18.5 kg/m²
  • eGFR less than 30 mL/min/1.73 m²
  • Type 1 diabetes, diabetic ketoacidosis, diabetic retinopathy, or poorly controlled diabetes with recurrent hypoglycemic episodes
  • Pancreatitis, history of pancreatitis, or pancreatic cancer
  • Multiple endocrine neoplasia type 2 or personal/family history of medullary thyroid cancer
  • Pre-existing significant gastrointestinal conditions such as inflammatory bowel disease or gastroparesis
  • Need for acute surgery
  • Other medical condition that may affect study procedures or participant safety
  • For optional adaptive neurostimulation: nonremovable metal in or around the head, known increased intracranial pressure due to infarcts or trauma, professional metal work or prior ocular metal injury, history of rTMS or ECT, or current (es)ketamine treatment

Treatment and study plan

Semaglutide (SEMA)

Drug

Once-weekly subcutaneous semaglutide for eligible participants with overweight or obesity and metabolic risk, titrated according to protocol up to 2.4 mg/week as tolerated, followed by tapering after Month 6.

Exercise module

Behavioral

Personalized moderate-intensity exercise intervention with supervised sessions during the structured phase and supported maintenance, targeting at least 150 minutes of moderate physical activity per week.

Anti-inflammatory diet module

Behavioral

Structured anti-inflammatory dietary intervention based on the Brain Anti-Inflammatory Nutrition (BrAIN) diet, supported by coaching, recipes, and digital materials.

Sleep intervention module

Behavioral

Adapted cognitive behavioral therapy for insomnia (SLEEPexpert) including a structured introduction and supported self-management.

Social prescribing module

Behavioral

Structured intervention to increase social participation, community engagement, and behavioral activation.

Closed-loop transcranial alternating current stimulation (CL-tACS)

Device

Optional adjunctive bifrontal closed-loop transcranial alternating current stimulation for participants with prominent depressive symptoms.

Structured lifestyle psychoeducation

Behavioral

Control intervention consisting of psychoeducation and counseling on lifestyle domains with self-guided continuation.

Sham CL-tACS

Device

Sham closed-loop transcranial alternating current stimulation in the control arm for eligible participants with prominent depressive symptoms.

Primary outcomes

  1. Change in Short Form 36 Health Survey (SF-36) Mental Component Summary (MCS) score

    Time frame: Baseline to Month 3

    Change from baseline in the SF-36 Mental Component Summary score.

Secondary outcomes

  1. Change in Short Form 36 Health Survey (SF-36) Mental Component Summary score (MCS) at Month 6

    Time frame: Baseline to Month 6

  2. Change in Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) score

    Time frame: Baseline to Month 3 and Month 6

  3. Change in Short Form 36 Health Survey (SF-36) total score

    Time frame: Baseline to Month 3 and Month 6

  4. Change in MATRICS Consensus Cognitive Battery

    Time frame: Baseline to Month 3 and Month 6

  5. Change in Insomnia Severity Index (ISI)

    Time frame: Baseline to Month 3 and Month 6

  6. Change in UCLA Loneliness Scale score

    Time frame: Baseline to Month 3 and Month 6

  7. Change in International Physical Activity Questionnaire

    Time frame: Baseline to Month 3 and Month 6

  8. Change in EQ-5D-3L score

    Time frame: Baseline to Month 3 and Month 6

  9. Incidence of adverse events and serious adverse events

    Time frame: Baseline through day 240-243

  10. Change in Brief Psychiatric Rating Scale (BPRS) psychotic symptoms

    Time frame: Baseline to Month 3 and Month 6

  11. Change in Montgomery-Åsberg Depression Rating Scale (MADRS)

    Time frame: Baseline to Month 3 and Month 6

  12. Change in Young Mania Rating Scale (YMRS)

    Time frame: Baseline to Month 3 and Month 6

  13. Change in Pittsburgh Sleep Quality Index (PSQI) scores

    Time frame: Baseline to Month 3 and Month 6

  14. Change in step aerobic test performance

    Time frame: Baseline to Month 3 and Month 6

  15. Change in grip strength

    Time frame: Baseline to Month 3 and Month 6

  16. Change in body weight

    Time frame: Baseline to Month 3 and Month 6

  17. Change in body mass index (BMI)

    Time frame: Baseline to Month 3 and Month 6

    Weight and height will be combined to report BMI in kg/m^2

  18. Change in waist-to-hip ratio

    Time frame: Baseline to Month 3 and Month 6

  19. Chage in blood pressure

    Time frame: Baseline to Month 3 and Month 6

  20. Change in lean mass

    Time frame: Baseline to Month 3 and Month 6

  21. Change in fat mass

    Time frame: Baseline to Month 3 and Month 6

Study contacts

Contact information is provided by the study sponsor or research team.

Peter Falkai, MD

CONTACT

[email protected]

+49 89 4400 - 55501

Sponsors and collaborators

Lead sponsor

Ludwig-Maximilians - University of Munich

Other

Registry information

Official study title

Personalised Pharmaco-Lifestyle Interventions for Severe Mental Illnesses Enhanced by Digital Health and Immersive Technologies

Acronym: LIFETRAIN

Important dates

Study start
2028
Primary completion
2030
Study completion
2030
First posted
May 14, 2026
Registry last updated
May 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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