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

NCT07586150 | Not Yet Recruiting

• 2 other identifiers: LIFETRAINU1111-1340-3272
• Study Type: interventional
• Target: 140
• Locations: 3 countries
• Sites: 5

Brief Summary

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.

Conditions

Bipolar Disorder (BD); Severe Mental Illness; Depression / Major Depressive Disorder; Schizophrenia

Outcome Measures

Primary Outcomes (1)

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

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

  Baseline to Month 3

Secondary Outcomes (21)

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

  Baseline to Month 6

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

  Baseline to Month 3 and Month 6

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

  Baseline to Month 3 and Month 6

• Change in MATRICS Consensus Cognitive Battery

  Baseline to Month 3 and Month 6

• Change in Insomnia Severity Index (ISI)

  Baseline to Month 3 and Month 6

Study Arms (2)

Personalized pharmaco-lifestyle intervention

EXPERIMENTAL

Participants receive one or more individualized intervention modules selected according to predefined eligibility criteria, digital guidance, and shared decision-making. Modules may include exercise, anti-inflammatory diet, sleep intervention, social prescribing, semaglutide, and optional closed-loop transcranial alternating current stimulation for participants with prominent depressive symptoms. Weekly guided support is provided through Month 3, followed by self-directed continuation with digital support through Month 6.

Drug: Semaglutide (SEMA); Behavioral: Exercise module; Behavioral: Anti-inflammatory diet module; Behavioral: Sleep intervention module; Behavioral: Social prescribing module; Device: Closed-loop transcranial alternating current stimulation (CL-tACS)

Structured lifestyle psychoeducation control

ACTIVE COMPARATOR

Participants receive structured psychoeducation and counseling on exercise, diet, sleep, and social contact approximately every four weeks through Month 3, followed by self-guided continuation through Month 6. Participants with prominent depressive symptoms may receive sham closed-loop transcranial alternating current stimulation.

Behavioral: Structured lifestyle psychoeducation; Device: Sham CL-tACS

Interventions

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.

Personalized pharmaco-lifestyle intervention

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.

Personalized pharmaco-lifestyle intervention

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.

Personalized pharmaco-lifestyle intervention

Sleep intervention module BEHAVIORAL

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

Personalized pharmaco-lifestyle intervention

Social prescribing module BEHAVIORAL

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

Personalized pharmaco-lifestyle intervention

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

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

Personalized pharmaco-lifestyle intervention

Structured lifestyle psychoeducation BEHAVIORAL

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

Structured lifestyle psychoeducation control

Sham CL-tACS DEVICE

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

Structured lifestyle psychoeducation control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (5)

Medical University of Vienna

Vienna, 1090, Austria

Location

Central Institute of Mental Health

Mannheim, 68159, Germany

Location

Department of Psychiatry and Psychotherapy, LMU Klinikum

München, 80336, Germany

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

MeSH Terms

Conditions

Mental Disorders; Depression; Depressive Disorder, Major; Bipolar Disorder; Schizophrenia

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Bipolar and Related Disorders; Schizophrenia Spectrum and Other Psychotic Disorders

Central Study Contacts

Peter Falkai, MD

CONTACT

+49 89 4400 - 55501; peter.falkai@med.uni-muenchen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to the nature of the behavioral and pharmacological interventions, participants and treating clinicians are not blinded to study arm assignment. Outcome assessors are blinded to treatment allocation. In the subgroup with prominent depressive symptoms, sham closed-loop transcranial alternating current stimulation is used in the control arm to reduce nonspecific procedural effects.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant, Department of Psychiatry and Psychotherapy, LMU University Hospital

Model Details: Participants are randomized in a parallel 1:1 design to either an individualized personalized intervention arm or an active control arm. Within the individualized intervention arm, participants may receive one or more intervention modules according to predefined eligibility criteria, digital decision support, and shared decision-making with the treating clinician.

Study Record Dates

• First Submitted: April 9, 2026
• First Posted: May 14, 2026
• Study Start (Estimated): October 1, 2028
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 14, 2026

Record last verified: 2026-05

Locations

NL (2); DE (2); AU (1)