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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.

Studie Overzicht

Toestand

Nog niet aan het werven

Studietype

Ingrijpend

Inschrijving (Geschat)

20

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Ja

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Intracellular lithium concentration in patient derived neural cells (hiNSCs) treated with LiG-AuNPs versus lithium salts (LiCl)
Tijdsspanne: 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)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Functional and biophysical differences
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Onderzoekers

  • Hoofdonderzoeker: Gabriele Sani, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 oktober 2026

Primaire voltooiing (Geschat)

30 september 2027

Studie voltooiing (Geschat)

31 maart 2029

Studieregistratiedata

Eerst ingediend

21 juli 2026

Eerst ingediend dat voldeed aan de QC-criteria

27 juli 2026

Eerst geplaatst (Werkelijk)

29 juli 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

29 juli 2026

Laatste update ingediend die voldeed aan QC-criteria

27 juli 2026

Laatst geverifieerd

1 juli 2026

Meer informatie

Termen gerelateerd aan deze studie

Andere studie-ID-nummers

  • RF-2024-12379870

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Beschrijving IPD-plan

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

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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