Bipolar DisorderDYSBIPNCT06167577
Dysbindin-antipsychotics Psychophamarcogenetics: a Mouse-human Translational Study Towards Personalized Healthcare in Bipolar Disorders
An observational study of Bipolar Disorder, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Psychometric scales (BPRS, MRS, HAM-D, SES, and GAF) monthly
- How many people
- 150 participants
- Where
- 1 siteItaly
- Study dates
- 8 Nov 2018to 8 Nov 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Bipolar disease patients who required therapy with an atypical antipsychotic in combination with a mood stabilizer
Who may be able to join
- 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.
Who cannot join
- Comorbidity with other psychiatric disorders;
- comorbidity with neurological disorders, with damage to the brain and with deficits intellectual;
- pregnancy;
- current and past substance abuse.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Milan, MI, 20100
About this study
Official title: Dysbindin-antipsychotics Psychophamarcogenetics: a Mouse-human Translational Study Towards Personalized Healthcare in Bipolar Disorders GR-2016-02362413
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).
Read the 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
- Being tested
- Psychometric scales (BPRS, MRS, HAM-D, SES, and GAF) monthly
- Keywords
- bipolar disorder, disbindina, antipsychotic
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psychometric scales (BPRS, MRS, HAM-D, SES, and GAF) monthlyDiagnostic test
Also called A single blood sample collection at study entry (T0) for the genotyping of the DTNBP1 gene (functional DysBray haplotype).
we will correlate the clinical/neuropsychological response to antipsychotics with the presence of the functional DysBray haplotype of the DTNBP1 gene
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2023
- Study start8 Nov 2018
- Primary completion8 Feb 2022
- Study completion8 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- ASST Santi Paolo e Carlo, Asst Melegnano e Martesana, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06167577
- Sponsor's protocol ID
- DYSBIP
- Acronym
- DYSBIP
- Status last verified
- Nov 2022
- First submitted
- 10 Nov 2023
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26388529Merikangas, K.R., et al. Archives of general psychiatry 68, 241-251 (2011).
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.
PubMed 23216388Ji, Y., et al. Proceedings of the National Academy of Sciences of the United States of America 106,19593-19598 (2009).
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.
PubMed 12923531Talbot 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.
PubMed 16980328Papaleo 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.
PubMed 20956979Papaleo, 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).
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.
PubMed 35328036
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dysbindin-antipsychotics Psychophamarcogenetics: a Mouse-human Translational Study Towards Personalized Healthcare in Bipolar Disorders GR-2016-02362413
- ClinicalTrials.gov ID
- NCT06167577
- Acronym / sponsor ID
- DYSBIP / DYSBIP
- Conditions
- Bipolar Disorder
- Keywords
- bipolar disorder, disbindina, antipsychotic
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Collaborators
- ASST Santi Paolo e Carlo, Asst Melegnano e Martesana, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
- Study start
- 8 Nov 2018 (actual)
- Primary completion
- 8 Feb 2022 (actual)
- Study completion
- 8 Nov 2023 (actual)
- First posted
- 12 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Bipolar disease patients who required therapy with an atypical antipsychotic in combination with a mood stabilizer
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (4 listed)
- Comorbidity with other psychiatric disorders;
- comorbidity with neurological disorders, with damage to the brain and with deficits intellectual;
- pregnancy;
- current and past substance abuse.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Psychometric scales (BPRS, MRS, HAM-D, SES, and GAF) monthlyAlso: A single blood sample collection at study entry (T0) for the genotyping of the DTNBP1 gene (functional DysBray haplotype).we will correlate the clinical/neuropsychological response to antipsychotics with the presence of the functional DysBray haplotype of the DTNBP1 gene | Diagnostic test | – |
Primary outcome
analyze the impact of genetic variants of the Disbindin-1 gene on patient's response to antipsychotic drugs
Time frame: 12 months
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- Background: PubMed 26388529Grande 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.
- BackgroundMerikangas, K.R., et al. Archives of general psychiatry 68, 241-251 (2011).
- Background: PubMed 23216388Hasan 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.
- BackgroundJi, Y., et al. Proceedings of the National Academy of Sciences of the United States of America 106,19593-19598 (2009).
- Background: PubMed 12923531Li 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.
- Background: PubMed 16980328Talbot 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.
- Background: PubMed 20956979Papaleo 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.
- BackgroundPapaleo, 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: PubMed 35328036Boscutti 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bipolar Disorder, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
analyze the impact of genetic variants of the Disbindin-1 gene on patient's response to antipsychotic drugs (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06167577, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.