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

NCT07732933 | Not Yet Recruiting

• 1 other identifier: RF-2024-12379870
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bipolar Disorder (BD); Bipolar Disorder (BPD)

Outcome Measures

Primary Outcomes (1)

• Intracellular lithium concentration in patient derived neural cells (hiNSCs) treated with LiG-AuNPs versus lithium salts (LiCl)

  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)

Secondary Outcomes (3)

• 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)

Study Arms (1)

Biological sample collection for iPSC/hiNSC generation

EXPERIMENTAL

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

Procedure: Peripheral blood sampling for PBMC isolation

Interventions

Peripheral blood sampling for PBMC isolation PROCEDURE

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.

Biological sample collection for iPSC/hiNSC generation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Related Publications (15)

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• De Chiara G, Piacentini R, Fabiani M, Mastrodonato A, Marcocci ME, Limongi D, Napoletani G, Protto V, Coluccio P, Celestino I, Li Puma DD, Grassi C, Palamara AT. Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice. PLoS Pathog. 2019 Mar 14;15(3):e1007617. doi: 10.1371/journal.ppat.1007617. eCollection 2019 Mar.

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Related Links

• Related Info

MeSH Terms

Conditions

Bipolar Disorder

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Study Officials

• Gabriele Sani

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gabriele Sani

CONTACT

+39 06 30155807; gabriele.sani@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2026
• First Posted: July 29, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): March 31, 2029
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)