GSK-3 as a Target for Lithium-charged Au Nanoparticles in Bipolar Disorder
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Intracellular lithium concentration in patient derived neural cells (hiNSCs) treated with LiG-AuNPs versus lithium salts (LiCl)
研究概览
简要总结
This preclinical translational study aims to evaluate a new method of delivering lithium using gold nanoparticles for the treatment of bipolar disorder. Lithium is an effective treatment for bipolar disorder, but its clinical use is limited by a narrow therapeutic range and the risk of side effects. The study will investigate whether gold nanoparticles carrying lithium can improve lithium delivery to brain cells while reducing exposure to other tissues.
The research will use human induced pluripotent stem cell (iPSC)-derived neural cells generated from blood samples collected from people with bipolar disorder and healthy volunteers, as well as a mouse model of mania. No participants will receive the investigational treatment. Human participants will provide blood samples only for the generation of laboratory cell models.
The study will compare the effects of nanoparticle-delivered lithium with conventional lithium salts on cellular lithium uptake, disease-related molecular and functional changes, and biomarkers associated with bipolar disorder. The hypothesis is that lithium delivered by gold nanoparticles will achieve greater therapeutic effects at lower systemic lithium exposure than conventional lithium formulations, providing proof of concept for a safer and more targeted lithium delivery strategy for future clinical development.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria for patients
- •Age: 18-65 years.
- •Diagnosis of Bipolar I or Bipolar II Disorder, according to DSM-5 criteria.
- •Currently in a depressive, manic, hypomanic, mixed, or euthymic phase, as defined by DSM-5 and clinical evaluation.
- •No use of psychotropic medications during the 12 months preceding enrollment, except for low-dose benzodiazepines or antipsychotics used intermittently to manage sleep disturbances or anxiety symptoms.
- •No prior treatment with lithium at any point in the patient's psychiatric history.
- •Medically stable and deemed suitable for study participation.
- •Ability and willingness to provide written informed consent before any study procedure For the Human Healthy Control group
- •participants aged 18-65 years will be included, while subjects with DSM-5 disorders or a family history of psychiatric disorders will be excluded.
排除标准
- •Current or past diagnosis of schizophrenia, schizoaffective disorder, or borderline personality disorder as the primary psychiatric condition.
- •Diagnosis of moderate to severe substance use disorder (excluding nicotine) within the past 12 months.
- •Active suicidal ideation with plan or intent
- •History of major neurological disorders, including epilepsy, traumatic brain injury, or neurodegenerative disease.
- •Previous exposure to lithium at any point in the individual's psychiatric history.
- •Use of psychotropic medication within the 12 months before enrollment.
- •Presence of uncontrolled or clinically significant medical conditions, including but not limited to severe hepatic, renal, or cardiovascular disease.
结局指标
主要结局
Intracellular lithium concentration in patient derived neural cells (hiNSCs) treated with LiG-AuNPs versus lithium salts (LiCl)
时间窗: 1, 2, 6, 12, and 24 hours after in vitro treatment (assessed throughout the 3-year study period)
Quantification of intracellular lithium load by Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) and subcellular gold nanoparticle distribution by Transmission Electron Microscopy (TEM) in neurons, astrocytes, and oligodendrocytes differentiated from participant-derived human induced Neural Stem Cells (hiNSCs), treated with Lithium-loaded, Glutathione-coated Gold Nanoparticles (LiG-AuNPs) or Lithium Chloride (LiCl) at concentrations of 0.15, 0.5, 1, 3, and 6 mEq/L, to compare uptake efficiency between the two delivery methods.
次要结局
- Functional and biophysical differences(Assessed at 30 days of in vitro differentiation (within the 3-year study period))
- Molecular biomarker expression in patient-derived neural cells(Assessed at 30 days of in vitro differentiation (within the 3-year study period))
- Blood biomarker profile in BD patients versus healthy controls(Baseline (single blood draw) and up to 24 hours after in vitro lithium exposure (within the 3-year study period))