A Study of the Behavioral Variant of Frontotemporal Dementia and Bipolar Disorder: a Neuroimaging and Epigenetics Integrated Approach

NCT06706687 | Recruiting

• 1 other identifier: DISBAND
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bipolar Disorder; Frontotemporal Dementia, Behavioral Variant

Keywords

Bipolar Disorder (BD); Frontotemporal Dementia, Behavioral Variant (bvFTD); Epigenetics; Neuroimaging; miRNA; Nuclear Magnetic Resonance Imaging (NMR); Nuclear Magnetic Resonance Spectroscopy (1H-MRS); Positron Emission Tomography (PET); Healthy controls (HC)

Outcome Measures

Primary Outcomes (8)

• 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

  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

  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

  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

  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

  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

  36 months

• Differences in brain metabolism

  Evaluation of the differences in brain metabolism comparing the three groups, using FDG/PET

  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

  36 months

Secondary Outcomes (1)

• Creation of a machine learning model

  36 months

Study Arms (3)

Frontotemporal Dementia, Behavioral Variant (bvFTD)

OTHER

Diagnostic Test: DISBAND protocol

Bipolar Disorder (BD)

OTHER

Diagnostic Test: DISBAND protocol

Healthy controls (HC)

OTHER

Diagnostic Test: DISBAND protocol

Interventions

DISBAND protocol DIAGNOSTIC_TEST

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.

Bipolar Disorder (BD); Frontotemporal Dementia, Behavioral Variant (bvFTD); Healthy controls (HC)

Eligibility Criteria

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

You may qualify if:

• byFTD group: patients of either sex; 18 years of age or older; diagnosis of behavioral variant Frontotemporal Dementia according to current diagnostic criteria; presence of a signed informed consent.
• BD group: patients of either sex; 18 years of age or older; diagnosis of bipolar disorder according to DSM-V criteria; presence of a signed informed consent.
• HC group: patients of either sex; 18 years of age or older; subjects who have gone through the same diagnostic process as patients under suspicion of a central nervous system and/or psychiatric disorder, resulting in the absence of cognitive deficits and mood disorders; presence of a signed informed consent.

You may not qualify if:

• Diagnosis of Alzheimer's disease
• Comorbidities interfering with the studied condition (e.g. other neurological diseases or history of substance or alcohol abuse)
• Diseases with an inflammatory component (e.g. autoimmune diseases, tumors)
• Pregnancy

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead

Study Sites (1)

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Milan, MI, 20100, Italy

RECRUITING

Related Publications (15)

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  PMID: 23473366 BACKGROUND

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• Baez S. et al., Neuropsychologia. 2017 Feb 17; S0028-3932(17)30058-1. doi: 10.1016/j.neuropsychologia.2017.02.012.

  BACKGROUND

• Delvecchio G. et al., Aust N Z J Psychiatry. 2018 Dec 13:4867418815976. doi: 10.1177/0004867418815976

  BACKGROUND

• Neueder A. et al, J Mol Biol. 2018 Dec 29; S0022-2836(18)31287-7. doi: 10.1016/j.jmb.2018.12.012.

  BACKGROUND

• Belzil VV, Gendron TF, Petrucelli L. RNA-mediated toxicity in neurodegenerative disease. Mol Cell Neurosci. 2013 Sep;56:406-19. doi: 10.1016/j.mcn.2012.12.006. Epub 2012 Dec 29.

  PMID: 23280309 BACKGROUND

• Rademakers R, Eriksen JL, Baker M, Robinson T, Ahmed Z, Lincoln SJ, Finch N, Rutherford NJ, Crook RJ, Josephs KA, Boeve BF, Knopman DS, Petersen RC, Parisi JE, Caselli RJ, Wszolek ZK, Uitti RJ, Feldman H, Hutton ML, Mackenzie IR, Graff-Radford NR, Dickson DW. Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum Mol Genet. 2008 Dec 1;17(23):3631-42. doi: 10.1093/hmg/ddn257. Epub 2008 Aug 21.

  PMID: 18723524 BACKGROUND

• Galimberti D, Villa C, Fenoglio C, Serpente M, Ghezzi L, Cioffi SM, Arighi A, Fumagalli G, Scarpini E. Circulating miRNAs as potential biomarkers in Alzheimer's disease. J Alzheimers Dis. 2014;42(4):1261-7. doi: 10.3233/JAD-140756.

  PMID: 25024331 BACKGROUND

• Fenoglio C, Ridolfi E, Galimberti D, Scarpini E. An emerging role for long non-coding RNA dysregulation in neurological disorders. Int J Mol Sci. 2013 Oct 14;14(10):20427-42. doi: 10.3390/ijms141020427.

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• Ludwig B, Dwivedi Y. Dissecting bipolar disorder complexity through epigenomic approach. Mol Psychiatry. 2016 Nov;21(11):1490-1498. doi: 10.1038/mp.2016.123. Epub 2016 Aug 2.

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• Jin XF, Wu N, Wang L, Li J. Circulating microRNAs: a novel class of potential biomarkers for diagnosing and prognosing central nervous system diseases. Cell Mol Neurobiol. 2013 Jul;33(5):601-13. doi: 10.1007/s10571-013-9940-9. Epub 2013 Apr 30.

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• Jun C, Choi Y, Lim SM, Bae S, Hong YS, Kim JE, Lyoo IK. Disturbance of the glutamatergic system in mood disorders. Exp Neurobiol. 2014 Mar;23(1):28-35. doi: 10.5607/en.2014.23.1.28. Epub 2014 Mar 27.

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MeSH Terms

Conditions

Bipolar Disorder; Pick Disease of the Brain; Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Elio Scarpini, Professor

  UOSD Malattie Neurodegenerative

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paolo Brambilla, Professor

CONTACT

02 55035982; paolo.brambilla@policlinico.mi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2024
• First Posted: November 26, 2024
• Study Start: May 19, 2021
• Primary Completion: January 1, 2025
• Study Completion: April 1, 2025
• Last Updated: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)