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

N/ANot Yet RecruitingNCT07586150

Ludwig-Maximilians - University of Munich140 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

140

Conditions

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

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.

Exercise moduleBEHAVIORAL

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 moduleBEHAVIORAL

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

Sleep intervention moduleBEHAVIORAL

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

Social prescribing moduleBEHAVIORAL

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 psychoeducationBEHAVIORAL

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

Sham CL-tACSDEVICE

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Baseline to Month 3