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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.

Aperçu de l'étude

Statut

Pas encore de recrutement

Type d'étude

Interventionnel

Inscription (Estimé)

20

Phase

  • N'est pas applicable

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Oui

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Intracellular lithium concentration in patient derived neural cells (hiNSCs) treated with LiG-AuNPs versus lithium salts (LiCl)
Délai: 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)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Functional and biophysical differences
Délai: 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
Délai: 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
Délai: 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)

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

  • Chercheur principal: Gabriele Sani, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 octobre 2026

Achèvement primaire (Estimé)

30 septembre 2027

Achèvement de l'étude (Estimé)

31 mars 2029

Dates d'inscription aux études

Première soumission

21 juillet 2026

Première soumission répondant aux critères de contrôle qualité

27 juillet 2026

Première publication (Réel)

29 juillet 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

29 juillet 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

27 juillet 2026

Dernière vérification

1 juillet 2026

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

  • RF-2024-12379870

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Description du régime IPD

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

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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