NCT06167577

Brief Summary

We will conduct an observational study involving a preliminary long-term follow-up designed to test how dysbindin-1 gene expression can modulate the efficacy of treatments with antipsychotics on clinical and neuropsychological outcomes. We will recruit 150 patients diagnosed with DB who required therapy with an atypical antipsychotic (aripiprazole or quetiapine or olanzapine) in combination with a medication mood stabilizer (lithium or other mood stabilizer), according to the standards of DB treatment. Treatment will be maintained stably for at least 6 months, unless the patient's clinical evolution makes a therapeutic switch inevitable. In light of the data in mice, we will correlate the clinical/neuropsychological response to antipsychotics with the presence of the functional DysBray haplotype of the DTNBP-1 gene, which has in the general population a relatively high prevalence (about 25 percent).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Nov 2018

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 8, 2018

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 8, 2022

Completed
1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 8, 2023

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

November 10, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

December 12, 2023

Completed
Last Updated

December 4, 2024

Status Verified

November 1, 2022

Enrollment Period

3.3 years

First QC Date

November 10, 2023

Last Update Submit

December 2, 2024

Conditions

Bipolar Disorder

Keywords

bipolar disorderdisbindinaantipsychotic

Outcome Measures

Primary Outcomes (1)

  • analyze the impact of genetic variants of the Disbindin-1 gene on patient's response to antipsychotic drugs

    Patients will undergo a follow-up lasting at least 12 months, during which we will we will record: Number and duration of illness relapses (hypomanic/manic, mixed or depressive), the number of emergency room admissions, hospitalizations, attempted suicide; Assessment of clinical and psychopathological status by psychometric scales (BPRS, MRS, HAM-D, SES and GAF) every month; Assessment of cognitive status through neuropsychological tests standardized (WAIS, BAC-A) every 6 months; A single blood sample collection at study entry (TO) for the DTNBP1 gene genotyping (DysBray functional haplotype (12).

    12 months

Interventions

Psychometric scales (BPRS, MRS, HAM-D, SES, and GAF) monthlyDIAGNOSTIC_TEST

we will correlate the clinical/neuropsychological response to antipsychotics with the presence of the functional DysBray haplotype of the DTNBP1 gene

Also known as: A single blood sample collection at study entry (T0) for the genotyping of the DTNBP1 gene (functional DysBray haplotype).

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Bipolar disease patients who required therapy with an atypical antipsychotic in combination with a mood stabilizer

You may qualify if:

  • DB diagnoses, made by the use of the structured clinical interview based on the DSM-5 criteria (SCID-CV);
  • Therapy with an atypical antipsychotic (aripiprazole or quetiapine or olanzapine) in combination with a mood stabilizer (lithium or another mood stabilizer mood), according to the standard of care.

You may not qualify if:

  • Comorbidity with other psychiatric disorders;
  • comorbidity with neurological disorders, with damage to the brain and with deficits intellectual;
  • pregnancy;
  • current and past substance abuse.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Milan, MI, 20100, Italy

Location

Related Publications (9)

  • Grande I, Berk M, Birmaher B, Vieta E. Bipolar disorder. Lancet. 2016 Apr 9;387(10027):1561-1572. doi: 10.1016/S0140-6736(15)00241-X. Epub 2015 Sep 18.

    PMID: 26388529BACKGROUND

  • Merikangas, K.R., et al. Archives of general psychiatry 68, 241-251 (2011).

    BACKGROUND

  • Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Thibaut F, Moller HJ; WFSBP Task force on Treatment Guidelines for Schizophrenia. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry. 2013 Feb;14(1):2-44. doi: 10.3109/15622975.2012.739708. Epub 2012 Dec 6.

    PMID: 23216388BACKGROUND

  • Ji, Y., et al. Proceedings of the National Academy of Sciences of the United States of America 106,19593-19598 (2009).

    BACKGROUND

  • Li W, Zhang Q, Oiso N, Novak EK, Gautam R, O'Brien EP, Tinsley CL, Blake DJ, Spritz RA, Copeland NG, Jenkins NA, Amato D, Roe BA, Starcevic M, Dell'Angelica EC, Elliott RW, Mishra V, Kingsmore SF, Paylor RE, Swank RT. Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Nat Genet. 2003 Sep;35(1):84-9. doi: 10.1038/ng1229. Epub 2003 Aug 17.

    PMID: 12923531BACKGROUND

  • Talbot K, Cho DS, Ong WY, Benson MA, Han LY, Kazi HA, Kamins J, Hahn CG, Blake DJ, Arnold SE. Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin. Hum Mol Genet. 2006 Oct 15;15(20):3041-54. doi: 10.1093/hmg/ddl246. Epub 2006 Sep 15.

    PMID: 16980328BACKGROUND

  • Papaleo F, Yang F, Garcia S, Chen J, Lu B, Crawley JN, Weinberger DR. Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways. Mol Psychiatry. 2012 Jan;17(1):85-98. doi: 10.1038/mp.2010.106. Epub 2010 Oct 19.

    PMID: 20956979BACKGROUND

  • Papaleo, F., Burdick, M.C., Callicott, J.H. & Weinberger, D.R. Mol Psychiatry 19, 311- 316(2014). 12. Bray, N.J.,et al. Hum Mol Genet 14, 1947-1954 (2005).

    BACKGROUND

  • Boscutti A, Pigoni A, Delvecchio G, Lazzaretti M, Mandolini GM, Girardi P, Ferro A, Sala M, Abbiati V, Cappucciati M, Bellani M, Perlini C, Rossetti MG, Balestrieri M, Damante G, Bonivento C, Rossi R, Finos L, Serretti A, Brambilla P, The Gecobip Group. The Influence of 5-HTTLPR, BDNF Rs6265 and COMT Rs4680 Polymorphisms on Impulsivity in Bipolar Disorder: The Role of Gender. Genes (Basel). 2022 Mar 9;13(3):482. doi: 10.3390/genes13030482.

    PMID: 35328036BACKGROUND

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Positron-Emission Tomography

Condition Hierarchy (Ancestors)

Bipolar and Related DisordersMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Tomography, Emission-ComputedImage Interpretation, Computer-AssistedDiagnostic ImagingDiagnostic Techniques and ProceduresDiagnosisImage EnhancementPhotographyRadionuclide ImagingTomographyDiagnostic Techniques, Radioisotope

Study Design

Study Type
observational
Observational Model
CASE ONLY
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 10, 2023

First Posted

December 12, 2023

Study Start

November 8, 2018

Primary Completion

February 8, 2022

Study Completion

November 8, 2023

Last Updated

December 4, 2024

Record last verified: 2022-11

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)