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Testing a New Gold Nanoparticle-Based Lithium Delivery Method for Bipolar Disorder in Laboratory Models (GLAD)

GSK-3 as a Target for Lithium-charged Au Nanoparticles in Bipolar Disorder

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.

研究概览

研究类型

介入性

注册 (估计的)

20

阶段

  • 不适用

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

学习地点

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

是的

描述

Inclusion Criteria:

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.

Exclusion Criteria:

  • 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.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Biological sample collection for iPSC/hiNSC generation
Includes both patients with Bipolar I or II Disorder (per DSM-5 criteria) and Human Healthy Controls (HC), recruited at the UOC of Clinical and Emergency Psychiatry, Fondazione Policlinico Universitario A. Gemelli IRCCS. All participants undergo the same peripheral blood sampling procedure, with no drug or device administered. The distinction between BD patients and healthy controls is defined by eligibility/diagnostic criteria, not by assignment or randomization to distinct arms
Blood collection in EDTA tubes for isolation of peripheral blood mononuclear cells (PBMCs), followed by reprogramming into induced pluripotent stem cells (iPSCs) via Sendai virus infection and differentiation into human induced neural stem cells (hiNSCs), used for the in vitro experiments of the protocol. No drug or device is administered to participants.

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Intracellular lithium concentration in patient derived neural cells (hiNSCs) treated with LiG-AuNPs versus lithium salts (LiCl)
大体时间: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.
1, 2, 6, 12, and 24 hours after in vitro treatment (assessed throughout the 3-year study period)

次要结果测量

结果测量
措施说明
大体时间
Functional and biophysical differences
大体时间:Assessed at 30 days of in vitro differentiation (within the 3-year study period)
Comparison of neuronal parameters (resting membrane potential, action potential threshold, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-D-aspartate (AMPA/NMDA) current ratio, frequency/amplitude of miniature excitatory postsynaptic currents, synaptic vesicle release) and astrocytic parameters (intracellular Ca²⁺ signaling, glutamate buffering/Excitatory Amino Acid Transporter 2 (EAAT2) activity, gliotransmitter release) between human induced Neural Stem Cell (hiNSC)-derived neurons/astrocytes from Bipolar Disorder (BD) patients versus healthy controls, before and after lithium exposure.
Assessed at 30 days of in vitro differentiation (within the 3-year study period)
Molecular biomarker expression in patient-derived neural cells
大体时间:Assessed at 30 days of in vitro differentiation (within the 3-year study period)
Levels of c-Fos, Synaptotagmin-7, Neuronal Pentraxin 2 (NPTX2), B-cell lymphoma 2 (Bcl-2), phospho-Glycogen Synthase Kinase 3 beta (GSK-3β)(Ser9)/total GSK-3β, and phospho-cytosolic Phospholipase A2 (cPLA2)(Ser505)/total cPLA2 in human induced Neural Stem Cell (hiNSC)-derived neurons and astrocytes from Bipolar Disorder (BD) patients.
Assessed at 30 days of in vitro differentiation (within the 3-year study period)
Blood biomarker profile in BD patients versus healthy controls
大体时间:Baseline (single blood draw) and up to 24 hours after in vitro lithium exposure (within the 3-year study period)
Plasma lithium levels, Thyroid Stimulating Hormone (TSH) levels, lithium load in blood cells, phospho-Glycogen Synthase Kinase 3 beta (pGSK-3β)(Ser9)/total GSK-3β ratio, and phospho-cytosolic Phospholipase A2 (cPLA2)(Ser505)/total cPLA2 levels, measured in blood cells and plasma from Bipolar Disorder (BD) patients (during the manic phase and again after standard lithium therapy) and from healthy controls, for comparison and biomarker identification.
Baseline (single blood draw) and up to 24 hours after in vitro lithium exposure (within the 3-year study period)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Gabriele Sani、Fondazione Policlinico Universitario Agostino Gemelli IRCCS

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年10月1日

初级完成 (估计的)

2027年9月30日

研究完成 (估计的)

2029年3月31日

研究注册日期

首次提交

2026年7月21日

首先提交符合 QC 标准的

2026年7月27日

首次发布 (实际的)

2026年7月29日

研究记录更新

最后更新发布 (实际的)

2026年7月29日

上次提交的符合 QC 标准的更新

2026年7月27日

最后验证

2026年7月1日

更多信息

与本研究相关的术语

其他研究编号

  • RF-2024-12379870

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

不

IPD 计划说明

Individual participant data will not be shared outside the research team due to the sensitive nature of the clinical, psychiatric, and biological data collected, including genetic and cellular material derived from patients with Bipolar Disorder. Data protection and confidentiality commitments made to participants during the informed consent process do not include provisions for external data sharing. Aggregate, de-identified results will be disseminated through peer-reviewed publications

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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