Dysbindin-antipsychotics Psychophamarcogenetics: a Mouse-human Translational Study Towards Personalized Healthcare in Bipolar Disorders

NCT ID: NCT06167577

Last Updated: 2024-12-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-11-08
• Study Completion Date: 2023-11-08

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).

Detailed Description

During the first visit, all subjects will sign informed consent and undergo a a clinical interview, in which clinical data will be collected. The demographic information will be transcribed into the electronic data collection form ("Electronic case report forms" - eCFR). The electronic data collection form should be completed at the time of the visit, so that it can objectively report the most recent observations. Each month recruited subjects will be administered specific scales (BPRS, YMRS, HAM-D, SES, GAF) validated in order to assess the psychopathological component. In addition, at the beginning of the study, a neuropsychological evaluation will be conducted to assess the cognitive status of the recruited patients. Therefore, neuropsychological tests will be administered. standardized (WAIS, BAC-A). In addition, neuropsychological assessments will be carried out as a follow-up (administration of the BAC-A) every 6 months, culminating in a follow-up of at least 12 months, to monitor the cognitive status of the subjects. Information obtained during the conduct of this clinical study is confidential and disclosure to third parties other than those indicated is strictly prohibited. The data collected (all information contained in original documents and certified copies or results clinical trials, observations or other activities in a clinical trial necessary for the reconstruction and evaluation of the study) will be archived in the file. The documents will be stored in a specific locked filing cabinet. The information collected will then be entered into a database, a management system (e.g., Microsoft Access). The data will be constantly backed up at the end of each week to prevent the loss of data that have been stored on the server. A server failure will cause delays in the execution phase of the analyses. The investigator must maintain all study records according to the guidelines on Good Clinical Practice (CGP) "International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)" and according to the record retention policies of the country in which the study. In accordance with the ICH/GCP guidelines, the investigator/institution will maintain all electronic resources and all original documents that support the data collected from each subject and all study documents (documents essential to the conduct of a study clinical trial). The investigator/institution will take measures to prevent the destruction accidental or premature destruction of these documents. Essential documents must be kept for at least 2 years after the end of the study.

Conditions

Bipolar Disorder

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Interventions

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

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

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

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

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ASST Santi Paolo e Carlo

OTHER

Sponsor Role: collaborator

Asst Melegnano e Martesana

OTHER_GOV

Sponsor Role: collaborator

Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria

OTHER

Sponsor Role: collaborator

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Milan, MI, Italy

Countries

Italy

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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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).

Reference Type: 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.

Reference Type: BACKGROUND

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Other Identifiers

DYSBIP

Identifier Type: -

Identifier Source: org_study_id