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

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

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

Interventions

DRUG

Semaglutide (SEMA)

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.

BEHAVIORAL

Exercise module

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.

BEHAVIORAL

Anti-inflammatory diet module

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

BEHAVIORAL

Sleep intervention module

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

BEHAVIORAL

Social prescribing module

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

DEVICE

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

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

BEHAVIORAL

Structured lifestyle psychoeducation

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

DEVICE

Sham CL-tACS

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

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2028-10-31

Primary Completion

2030-07-31

Completion

2030-12-31

Countries

• Austria
• Germany
• Netherlands

Study Locations