Selenium Supplementation for Improving Depression in Children and Adolescents: Efficacy and Mechanistic Study

Обзор

The purpose of this study is to investigate the role and mechanisms of selenium in depression among children and adolescents, aiming to provide new insights for understanding the pathogenesis and treatment of depression in this population.

Подробное описание

This randomized, double-blind, placebo-controlled trial will evaluate the efficacy and safety of selenium supplementation (selenium yeast) combined with fluoxetine in children and adolescents with major depressive disorder (MDD). Eligible participants are aged \[specific age range if applicable\], meet DSM-5 criteria for a current depressive episode, and have a CDRS-R score ≥40 confirmed by trained psychiatrists. A total of \[planned sample size\] participants will be randomized 1:1 to receive either fluoxetine plus selenium yeast or fluoxetine plus placebo. Selenium yeast will be administered at 60-200 μg/day. Fluoxetine will begin at 10 mg/day and may be adjusted by the treating psychiatrist within a range of 20-60 mg/day. The placebo consists of commercially available yeast tablets identical in appearance, taste, and size to selenium yeast, administered at 60-200 μg/day. Biological samples (blood, urine, stool) will be collected for routine laboratory tests, thyroid, liver, and kidney function, and serum will be analyzed for selenium and ferroptosis-related biomarkers. Brain MRI will also be performed. These assessments will be repeated at weeks 4 and 8 of treatment, together with rating scale evaluations and biospecimen collection. The primary outcome is the change in depressive symptoms, measured by the CDRS-R and Beck Depression Inventory (BDI). Secondary outcomes include anxiety symptoms (SCARED, HAMA), overall clinical improvement (CGI-S, CGI-I), manic symptoms (YMRS), suicide risk (C-SSRS), quality of life (PedsQL 4.0), sleep quality (PSQI), and rumination (RSS). Safety will be monitored through adverse events, vital signs, laboratory tests, and tolerability assessments. This study will provide preliminary evidence on the adjunctive role of selenium supplementation in fluoxetine treatment for adolescent depression and inform future large-scale trials.

Вмешательства

• Препарат selenium yeast supplementation
  In this intervention, patients will receive adjunctive selenium yeast supplementation at a daily dose of 60-200 μg in addition to fluoxetine. Symptom rating scales, biospecimen collection, and brain MRI will be conducted at baseline, week 4, and week 8 to investigate the adjunctive role of selenium in fluoxetine treatment for depression.
• Препарат Placebo yeast supplementation
  In this intervention, patients will receive standard fluoxetine treatment combined with placebo yeast supplementation (60-200 μg/day), which is identical in appearance and odor to selenium yeast. The aim is to clarify the specific role of selenium in the treatment of depression.

Первичные конечные точки

• Change in CDRS-R (Children's Depression Rating Scale) scores from baseline [Срок оценки: Week 4 and Week 8 of treatment]

Вторичные конечные точки (8)

• Change in BDI-II (Baker Depression Scale) scores from baseline [Срок оценки: Week 4 and Week 8 of treatment]
• Change in SCARED (The Screen for Child Anxiety-Related Emotional Disorders) scores from baseline [Срок оценки: Week 4 and Week 8 of treatment]
• Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale) [Срок оценки: Week 4 and Week 8 of treatment]
• Change in PSQI (Pittsburgh Sleep Quality Index) scores from baseline [Срок оценки: Week 4 and Week 8 of treatment]
• Change in PedsQL4.0 (The Pediatric Quality of Life Inventory) scores from baseline [Срок оценки: Week 4 and Week 8 of treatment]
• Change in CGI-S (Clinical Global Impressions-Severity Scales) scores from baseline [Срок оценки: Week 4 and Week 8 of treatment]
• Change in CGI-I (Clinical Global Impressions-Improvement Scales) scores from baseline [Срок оценки: Week 4 and Week 8 of treatment]
• Change in RSS (Ruminative Responses Scale) [Срок оценки: Week 4 and Week 8 of treatment]

Критерии участия

Критерии включения

• Aged 12-18 years;
• Diagnosed with major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), using the K-SADS-PL diagnostic tool;
• A score of ≥28 on the Children's Depression Rating Scale-Revised (CDRS-R);
• Adequate visual and auditory abilities to complete the study;
• Willingness to participate in the study with informed consent signed by both the participant and a legal guardian.

Критерии исключения

• Patients with severe psychiatric disorders such as bipolar disorder, schizophrenia, bulimia nervosa, anorexia nervosa, or primary obsessive-compulsive disorder;
• Those with severe physical illnesses or other life-threatening conditions; patients in a current depressive episode with a clear suicidal plan or history of suicide attempt;
• Individuals with a history of substance or drug abuse;
• Those requiring immediate hospitalization for psychiatric disorders;
• Patients currently taking medications contraindicated with the investigational drug or that may interfere with its efficacy;
• Those who have received modified electroconvulsive therapy (MECT) within the past 12 months;
• Individuals allergic to selenium yeast protein, including those with allergic rhinitis, gastrointestinal sensitivity, allergic constitution, or autoimmune diseases such as Graves' disease or Hashimoto's thyroiditis;
• Patients with contraindications to magnetic resonance imaging (MRI);
• Aand left-handed individuals.

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Chongqing Medical University — Чунцин

Публикации

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• Hankin BL. Depression from childhood through adolescence: Risk mechanisms across multiple systems and levels of analysis. Curr Opin Psychol. 2015 Aug;4:13-20. doi: 10.1016/j.copsyc.2015.01.003. PMID 25692174
• Consoli A, Peyre H, Speranza M, Hassler C, Falissard B, Touchette E, Cohen D, Moro MR, Revah-Levy A. Suicidal behaviors in depressed adolescents: role of perceived relationships in the family. Child Adolesc Psychiatry Ment Health. 2013 Mar 16;7(1):8. doi: 10.1186/1753-2000-7-8. PMID 23497551
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• Cipriani A, Zhou X, Del Giovane C, Hetrick SE, Qin B, Whittington C, Coghill D, Zhang Y, Hazell P, Leucht S, Cuijpers P, Pu J, Cohen D, Ravindran AV, Liu Y, Michael KD, Yang L, Liu L, Xie P. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet. 2016 Aug 27;388(10047):881-90. doi: 10.1016/S0140-6736(16)30 PMID 27289172
• Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN. Characterization of mammalian selenoproteomes. Science. 2003 May 30;300(5624):1439-43. doi: 10.1126/science.1083516. PMID 12775843
• Rayman MP. Selenium and human health. Lancet. 2012 Mar 31;379(9822):1256-68. doi: 10.1016/S0140-6736(11)61452-9. Epub 2012 Feb 29. PMID 22381456
• Dang R, Wang M, Li X, Wang H, Liu L, Wu Q, Zhao J, Ji P, Zhong L, Licinio J, Xie P. Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway. J Neuroinflammation. 2022 Feb 7;19(1):41. doi: 10.1186/s12974-022-02400-6. PMID 35130906

Идентификаторы

NCT: NCT07203144 · 1stChongqingMU---ZXY

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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