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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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.
• Поведенческое 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.
• Поведенческое 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.
• Поведенческое Sleep intervention module
  Adapted cognitive behavioral therapy for insomnia (SLEEPexpert) including a structured introduction and supported self-management.
• Поведенческое Social prescribing module
  Structured intervention to increase social participation, community engagement, and behavioral activation.
• Устройство Closed-loop transcranial alternating current stimulation (CL-tACS)
  Optional adjunctive bifrontal closed-loop transcranial alternating current stimulation for participants with prominent depressive symptoms.
• Поведенческое Structured lifestyle psychoeducation
  Control intervention consisting of psychoeducation and counseling on lifestyle domains with self-guided continuation.
• Устройство Sham CL-tACS
  Sham closed-loop transcranial alternating current stimulation in the control arm for eligible participants with prominent depressive symptoms.

Первичные конечные точки

• Change in Short Form 36 Health Survey (SF-36) Mental Component Summary (MCS) score [Срок оценки: Baseline to Month 3]

Вторичные конечные точки (12)

• Change in Short Form 36 Health Survey (SF-36) Mental Component Summary score (MCS) at Month 6 [Срок оценки: Baseline to Month 6]
• Change in Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) score [Срок оценки: Baseline to Month 3 and Month 6]
• Change in Short Form 36 Health Survey (SF-36) total score [Срок оценки: Baseline to Month 3 and Month 6]
• Change in MATRICS Consensus Cognitive Battery [Срок оценки: Baseline to Month 3 and Month 6]
• Change in Insomnia Severity Index (ISI) [Срок оценки: Baseline to Month 3 and Month 6]
• Change in UCLA Loneliness Scale score [Срок оценки: Baseline to Month 3 and Month 6]
• Change in International Physical Activity Questionnaire [Срок оценки: Baseline to Month 3 and Month 6]
• Change in EQ-5D-3L score [Срок оценки: Baseline to Month 3 and Month 6]
• Incidence of adverse events and serious adverse events [Срок оценки: Baseline through day 240-243]
• Change in Brief Psychiatric Rating Scale (BPRS) psychotic symptoms [Срок оценки: Baseline to Month 3 and Month 6]
• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) [Срок оценки: Baseline to Month 3 and Month 6]
• Change in Young Mania Rating Scale (YMRS) [Срок оценки: Baseline to Month 3 and Month 6]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Германия · 2 центра

• Central Institute of Mental Health — Mannheim
• Department of Psychiatry and Psychotherapy, LMU Klinikum — München

Нидерланды · 2 центра

• University Medical Center Groningen — Groningen
• University Medical Center Utrecht — Utrecht

Австрия · 1 центр

• Medical University of Vienna — Vienna

Идентификаторы

NCT: NCT07586150 · LIFETRAIN · U1111-1340-3272

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗