An interventional study of DISBAND protocol in Bipolar Disorder and Frontotemporal Dementia, Behavioral Variant, sponsored by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-11-26.
Sponsored by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico · Not applicable, Interventional, and Other
The aim of this study is to investigate the selective epigenetic modifications and their effect on brain's morphology and functionality in the frontotemporal dementia behavioral variant and bipolar disorder. The open-label, multicentric, interventional case-control study involves the analysis of 3 separate cohorts of patients, partly selected over the course of the past 10 years. More specifically, 80 behavioral variant Frontotemporal Dementia (bvFTD) patients (40, of whom 20 carry G4C2 expansion in the C9orf72 gene, are already available, while 40 will be prospectively recruited), 80 Bipolar Disorder (BD) patients (40, including 20 with early onset and 20 with late onset, are already available, while 40 will be prospectively recruited) and 50 healthy control (HC) subjects (20 of whom are already available from other previously approved studies), will be enrolled in this study.
For each participant a blood sample will be collected, processed, and studied in order analyze the expression of miRNA. Every participant will also undergo Nuclear Magnetic Resonance Imaging (NMR), Nuclear Magnetic Resonance Spectroscopy (1H-MRS), and Positron Emission Tomography (PET) and, lastly, a battery of behavioral scales to explore different cognitive domains will be administered to all participants by a team of psychologists and physicians. The overall estimated duration of the study is 36 months.
Following the inclusion and exclusion criteria, the participants will be recruited and subdivided into three groups:
The investigators will be collecting participants blood samples, which will be processed and analyzed. More specifically, total exosomes will be isolated from 500 microliters of plasma by ExoQuick precipitation solution (SBI). Isolation and purification of NDEs will be performed by ExoFlow purification kit using biotinylated anti-human CD171 (L1CAM) antibody (clone 5G3, Ebiosciences). Total RNA contained in NDEs will be extracted by Total Exosome RNA and Protein Isolation Kit and miRNA expression analysis by TaqMan OpenArray Human Advanced MicroRNA Panel (Thermo Fisher Scientific). Expression analysis of lncRNAs will be conducted by LincFinder Array and inflammatory and autoimmunity arrays (Qiagen).
The participants will also undergo a neuroimaging session, where structural MRI and 1H-MRS sessions will be performed using a 3T MRI scanner available at the Neuroradiology Unit. The 1H-MRS will provide sensitive and reliable assessment of neurochemical changes in specific brain areas. The acquisition voxels will be palced in the dorso- and ventrolateral prefrontal cortex (DLPFC/VLPFC), amygdala, and hippocampus. Finally, an FDG-PET scan will be performed with a Biograph Truepoint 64 PET/TC scanner. T1-weighted and FDG-PET images will be used to explore brain morphological/metabolic differences between the groups. Gray matter and white matter volumes will be estimated locally and compared between groups using voxel-based morphometry. A parallel region of interest comparison (ROIs) will be performed to estimate regional volumes using the Automated Anatomical Labelling (AAL) atlas as a reference, again focusing on the DLPFC/VLPFC, amygdala and hippocampus. Finally, an additional regional analysis based on Freesurfer software will allow the investigators to estimate the cortical thickness, cortical surface area, and cortical gyrification of the Desikan-Killiany atlas regions. All MRI and PET analyses will be performed in the context of a general linear model using a specific software implementation in MATLAB called Statistical Parametric Mapping (SPM).
Lastly, neuroimaging data and ncRNA expression profiles will be used as predictors in the ML analysis. Given the small sample size, initially linear models (e.g., Support Vector Machine) will be used. Later, to improve the predictive power of our models, the investigators will apply the ML method called random forest, a more versatile and powerful classification algorithm, and the XGBoost (eXtreme Gradient Boosting) algorithm. To avoid overfitting of the learning process, a "grid" search of model hyperparameters will be performed. A 5-fold cross-validation will be used to validate the results, with a split between training-tests of 80%-20%.
1,637 studies on the registry are indexed under Bipolar Disorder; 258 are open to participants now.
This study's planned enrollment of 210 is above the median of 63 across 1,245 interventional studies indexed under Bipolar Disorder.
Browse Bipolar Disorder studies →Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico is the lead sponsor of 232 studies on the registry; 83 are open to participants now.
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Exclusion Criteria:
Diagnostic Test: DISBAND protocol
Diagnostic Test: DISBAND protocol
Diagnostic Test: DISBAND protocol
For each participant blood samples will be collected, processed and studied to analyse microRNA expression, more specifically investigating non-coding RNA (ncRNA). Each participant will undergo a multimodal neuroimaging session, composed of structural MRI, 1H-MRS and PET.
Identification of ncRNA transcripts and a specific noncoding RNA profile in neuron-derived exosomes
Identification of ncRNA transcripts and a specific noncoding RNA profile in neuron-derived exosomes in patients with bvFTD and BD
Time frame: 36 months
Differences in brain structure in terms of white matter volumes
Evaluation of the differences in brain structure in terms of white matter volumes comparing the three groups, using structural MRI
Time frame: 36 months
Differences in brain structure in terms of gray matter volumes
Evaluation of the differences in brain structure in terms of gray matter volumes comparing the three groups, using structural MRI
Time frame: 36 months
Differences in brain structure in terms of cortical gyrification
Evaluation of the differences in brain structure in terms of cortical gyrification comparing the three groups, using structural MRI
Time frame: 36 months
Differences in brain structure in terms of superficial cortical area
Evaluation of the differences in brain structure in terms of superficial cortical area comparing the three groups, using structural MRI
Time frame: 36 months
Differences in brain structure in terms of cortical thickness
Evaluation of the differences in brain structure in terms of cortical thickness comparing the three groups, using structural MRI
Time frame: 36 months
Differences in brain metabolism
Evaluation of the differences in brain metabolism comparing the three groups, using FDG/PET
Time frame: 36 months
Differences in glutamatergic neurotransmission in the prefrontal-limbic cortex
Evaluation of the differences in the glutamatergic neurotransmission of the prefrontal-limbic cortex, comparing the three groups, using 1H-MRS
Time frame: 36 months
Creation of a machine learning model
Creation of a machine learning model that could integrate neuroimaging data and miRNA expression data to validate the best candidates identified combining imaging and epigenetic data
Time frame: 36 months
Plan to share: No
Started May 2021 (actual). Primary completion is estimated for Jan 2025, 44 months after the start.
Of 348 non-industry interventional studies with no phase under Bipolar Disorder, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 23 and three quarters within 58. This study's planned 44 months is above that.
Counting every sponsor, half of 349 studies reached it within 39 months; a quarter within 23 and three quarters within 58.
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