Brain Voxel-based Morphometry in ManiaNCT03181698
Brain Voxel-based Morphometry in Bipolar Mania
An observational study of Brain Voxel-based Morphometry in Mania, run by Assiut University at 1 site in Egypt.
Trial summary
Bipolar disorder is a complex psychiatric disorder characterized by recurrent episodes of mania or hypomania and depression, and affects around one to three percent of the population . Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Brain Voxel-based Morphometry in Mania
- What is being tested?
- Magnetic resonance imaging
- How many people
- 45 participants
- Where
- 1 siteEgypt
- Study dates
- 22 Sep 2017to 11 Sep 2018
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: patients diagnosed to have mood disorder Bipolar I mania with or without psychotic features according to criteria of Diagnostic and Statistical Manual of Mental disorders-IV by psychiatric sheath of psychiatric unit at Assiut University hospital . and sex and age-matched healthy subjects
Who may be able to join
- clinically diagnosed to have mood disorder Bipolar I mania with or without psychotic features according to criteria of Diagnostic and Statistical Manual of Mental disorders-IV by psychiatric sheath of psychiatric unit at Assiut University hospital .
Who cannot join
- first and second degree relatives of psychiatric patients will be excluded from the healthy controls.
- Persons with any neurological disorder or other psychiatric illness will be excluded from controls
- Patients with proven major structural abnormality as detected during Magnetic Resonance Imaging examination will be excluded from patients or healthy controls.
- -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Differences in Voxel-based Morphometry of Different Brain Structures in Patients With Mood Disorder Bipolar Mania in Comparison to Morphometry of Nrmal Controls
Bipolar disorder is a complex psychiatric disorder characterized by recurrent episodes of mania or hypomania and depression, and affects around one to three percent of the population . Bipolar Disorder is associated with significant psychosocial morbidity and mortality , and is among the leading causes of disability worldwide . The disease is highly heritable, but the underlying pathophysiology is not yet understood .
Read the detailed description
It is recognized that lesions in some specific neuro-anatomic areas due to brain disease, e.g., stroke or brain tumor, may lead to the development of secondary depression. The possibility of structural brain abnormalities as a cause of depression stimulated the use of structural brain imaging studies. Developments in structural neuroimaging by computed tomography and magnetic resonance imaging in the past 15 years facilitated the direct examination of specific brain structures, making the study of the relationship between anatomy and psychopathology is possible.
Neuro-anatomic model of mood regulation :
The prefrontal cortex has extensive connectivity to cortical and subcortical circuits that may underlie its importance in cognitive functions and modulation of limbic activity .The main subcortical structures participating in these circuits are the basal ganglia, thalamus, hypothalamus, brainstem, and the white matter tracts that connect these structures among themselves and to the cerebral cortex . A limbic-thalamic-cortical circuit consisting of the amygdala, the medio-dorsal nucleus of the thalamus, and the medial and ventro-lateral prefrontal cortex, and a limbic-striato-pallidal-thalamic circuit comprising the striatum, the ventral pallidum, and the components of the other circuit are the main neuro-anatomic circuits that have been proposed to participate in the pathophysiology of mood disorders.
The basal ganglia connect with cortical and limbic regions through circuits that, despite functioning segregated, are organized in parallel , in such a way that lesions in different parts of these circuits could result in malfunction. Additionally, the cerebellum, through connections with the brainstem and limbic structures, may also be involved in mood regulation.
Both primary and secondary mood disorders may involve abnormalities in specific fronto-subcortical neuro-anatomic circuits. Abnormalities in these brain regions or in contiguous areas that can affect the connections between these regions could reflect malfunction of these circuits, associated with development of mood disorders. Alternatively, abnormalities in these circuits could confer vulnerability to mood disorders, and its onset could be determined by interactions with environmental and genetic factors. Deficits during brain development due to these factors could result in under-development of particular brain areas, which could be related subsequently with mood disorders. The aging process or pathology such as vascular brain disease could result in atrophy of some of these regions. Thus, the influence of genetic, environmental, developmental, and degenerative factors during the development of these brain structures may determine the onset of mood disorders .
Although structural brain abnormalities in Bipolar Disorder have been reported, the pattern of structural brain abnormalities based on magnetic resonance imaging is still not clearly defined.
Aim of the study :
To study the morphometric criteria of different brain structures in patients with Bipolar Disorder type I mania in comparison to healthy subjects.
Subjects and Methods:
Patients :
Inclusion criteria:
Patients diagnosed to have mood disorder Bipolar I mania with or without psychotic features according to criteria of Diagnostic and statistical Manual of Mental disorder-IV (American Psychiatric Association 1994) by psychiatric sheath of psychiatric unit at Assiut University hospital .
The patients will be arranged in Two subgroups:
first group: twenty five patients in more than one episode second group: twenty age and sex-matched healthy subjects will be enrolled in the study
.
Exclusion Criteria:
first and second degree relatives of psychiatric patients will be excluded from the healthy controls.
Persons with any neurological disorder or other psychiatric illness will be excluded from controls Patients with proven major structural abnormality as detected during Magnetic resonance Imaging Examination will be excluded from patients or healthy controls.
- Conditions
- Brain Voxel-based Morphometry in Mania
- Being tested
- Magnetic resonance imaging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic resonance imagingDiagnostic test
A full Magnetic Resonance Imaging examination of the brain will be done for each of the subjects included in the study. The protocol of the study will include a high-resolution thin-cuts three Dimensions-T1 weighted gradient echo sequence to be used for the morphometric study.
The obtained images will be analyzed for any gross structural abnormalities. by using fully-automated computational voxel-based volumetric software that calculates the volume of different structures of the brain. The obtained data will be analyzed statistically using linear regression tests to determine the differences between Bipolar Disorder type I mania patients and the healthy controls
| Study group | Role | What they receive |
|---|---|---|
| first group | patients with more than one episodes of mania Receives: Diagnostic Test: Magnetic resonance imaging | |
| second group | sex-matched and age- matched healthy controls Receives: Diagnostic Test: Magnetic resonance imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
mean differences in measurements of different brain structures
mean differences in measurements of brain structures between patients of Mania and Healthy controls by using standard of all statistical parametric brain mapping-based processing software.voxels typically represent a volume of 27 mm3 (a cube with 3mm length sides)
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2017
- Study start22 Sep 2017
- Primary completion14 Jul 2018
- Study completion11 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Brain Voxel-based Morphometry in ManiaStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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-control
- Time perspective
- Prospective
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shaza Ragab, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03181698
- Sponsor's protocol ID
- VBM MANIA
- Status last verified
- Jun 2020
- First submitted
- 6 Jun 2017
- Last updated
- 18 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hibar DP, Westlye LT, van Erp TG, Rasmussen J, Leonardo CD, Faskowitz J, Haukvik UK, Hartberg CB, Doan NT, Agartz I, Dale AM, Gruber O, Kramer B, Trost S, Liberg B, Abe C, Ekman CJ, Ingvar M, Landen M, Fears SC, Freimer NB, Bearden CE; Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes; Sprooten E, Glahn DC, Pearlson GD, Emsell L, Kenney J, Scanlon C, McDonald C, Cannon DM, Almeida J, Versace A, Caseras X, Lawrence NS, Phillips ML, Dima D, Delvecchio G, Frangou S, Satterthwaite TD, Wolf D, Houenou J, Henry C, Malt UF, Boen E, Elvsashagen T, Young AH, Lloyd AJ, Goodwin GM, Mackay CE, Bourne C, Bilderbeck A, Abramovic L, Boks MP, van Haren NE, Ophoff RA, Kahn RS, Bauer M, Pfennig A, Alda M, Hajek T, Mwangi B, Soares JC, Nickson T, Dimitrova R, Sussmann JE, Hagenaars S, Whalley HC, McIntosh AM, Thompson PM, Andreassen OA. Subcortical volumetric abnormalities in bipolar disorder. Mol Psychiatry. 2016 Dec;21(12):1710-1716. doi: 10.1038/mp.2015.227. Epub 2016 Feb 9.
PubMed 26857596Angst F, Stassen HH, Clayton PJ, Angst J. Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord. 2002 Apr;68(2-3):167-81. doi: 10.1016/s0165-0327(01)00377-9.
PubMed 12063145Tondo L, Isacsson G, Baldessarini R. Suicidal behaviour in bipolar disorder: risk and prevention. CNS Drugs. 2003;17(7):491-511. doi: 10.2165/00023210-200317070-00003.
PubMed 12751919Rocha-Rego V, Jogia J, Marquand AF, Mourao-Miranda J, Simmons A, Frangou S. Examination of the predictive value of structural magnetic resonance scans in bipolar disorder: a pattern classification approach. Psychol Med. 2014 Feb;44(3):519-32. doi: 10.1017/S0033291713001013. Epub 2013 Jun 5.
PubMed 23734914Soares JC, Mann JJ. The anatomy of mood disorders--review of structural neuroimaging studies. Biol Psychiatry. 1997 Jan 1;41(1):86-106. doi: 10.1016/s0006-3223(96)00006-6.
PubMed 8988799Lipska BK, Jaskiw GE, Weinberger DR. Postpubertal emergence of hyperresponsiveness to stress and to amphetamine after neonatal excitotoxic hippocampal damage: a potential animal model of schizophrenia. Neuropsychopharmacology. 1993 Aug;9(1):67-75. doi: 10.1038/npp.1993.44.
PubMed 8397725Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990 Jul;13(7):266-71. doi: 10.1016/0166-2236(90)90107-l.
PubMed 1695401
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Differences in Voxel-based Morphometry of Different Brain Structures in Patients With Mood Disorder Bipolar Mania in Comparison to Morphometry of Nrmal Controls
- ClinicalTrials.gov ID
- NCT03181698
- Acronym / sponsor ID
- VBM MANIA
- Conditions
- Brain Voxel-based Morphometry in Mania
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 22 Sep 2017 (actual)
- Primary completion
- 14 Jul 2018 (actual)
- Study completion
- 11 Sep 2018 (actual)
- First posted
- 9 Jun 2017 (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.
Bipolar disorder is a complex psychiatric disorder characterized by recurrent episodes of mania or hypomania and depression, and affects around one to three percent of the population . Bipolar Disorder is associated with significant psychosocial morbidity and mortality , and is among the leading causes of disability worldwide . The disease is highly heritable, but the underlying pathophysiology is not yet understood .
Detailed description
It is recognized that lesions in some specific neuro-anatomic areas due to brain disease, e.g., stroke or brain tumor, may lead to the development of secondary depression. The possibility of structural brain abnormalities as a cause of depression stimulated the use of structural brain imaging studies. Developments in structural neuroimaging by computed tomography and magnetic resonance imaging in the past 15 years facilitated the direct examination of specific brain structures, making the study of the relationship between anatomy and psychopathology is possible.
Neuro-anatomic model of mood regulation :
The prefrontal cortex has extensive connectivity to cortical and subcortical circuits that may underlie its importance in cognitive functions and modulation of limbic activity .The main subcortical structures participating in these circuits are the basal ganglia, thalamus, hypothalamus, brainstem, and the white matter tracts that connect these structures among themselves and to the cerebral cortex . A limbic-thalamic-cortical circuit consisting of the amygdala, the medio-dorsal nucleus of the thalamus, and the medial and ventro-lateral prefrontal cortex, and a limbic-striato-pallidal-thalamic circuit comprising the striatum, the ventral pallidum, and the components of the other circuit are the main neuro-anatomic circuits that have been proposed to participate in the pathophysiology of mood disorders.
The basal ganglia connect with cortical and limbic regions through circuits that, despite functioning segregated, are organized in parallel , in such a way that lesions in different parts of these circuits could result in malfunction. Additionally, the cerebellum, through connections with the brainstem and limbic structures, may also be involved in mood regulation.
Both primary and secondary mood disorders may involve abnormalities in specific fronto-subcortical neuro-anatomic circuits. Abnormalities in these brain regions or in contiguous areas that can affect the connections between these regions could reflect malfunction of these circuits, associated with development of mood disorders. Alternatively, abnormalities in these circuits could confer vulnerability to mood disorders, and its onset could be determined by interactions with environmental and genetic factors. Deficits during brain development due to these factors could result in under-development of particular brain areas, which could be related subsequently with mood disorders. The aging process or pathology such as vascular brain disease could result in atrophy of some of these regions. Thus, the influence of genetic, environmental, developmental, and degenerative factors during the development of these brain structures may determine the onset of mood disorders .
Although structural brain abnormalities in Bipolar Disorder have been reported, the pattern of structural brain abnormalities based on magnetic resonance imaging is still not clearly defined.
Aim of the study :
To study the morphometric criteria of different brain structures in patients with Bipolar Disorder type I mania in comparison to healthy subjects.
Subjects and Methods:
Patients :
Inclusion criteria:
Patients diagnosed to have mood disorder Bipolar I mania with or without psychotic features according to criteria of Diagnostic and statistical Manual of Mental disorder-IV (American Psychiatric Association 1994) by psychiatric sheath of psychiatric unit at Assiut University hospital .
The patients will be arranged in Two subgroups:
first group: twenty five patients in more than one episode second group: twenty age and sex-matched healthy subjects will be enrolled in the study
.
Exclusion Criteria:
first and second degree relatives of psychiatric patients will be excluded from the healthy controls.
Persons with any neurological disorder or other psychiatric illness will be excluded from controls Patients with proven major structural abnormality as detected during Magnetic resonance Imaging Examination will be excluded from patients or healthy controls.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| first group | – | Diagnostic Test: Magnetic resonance imagingpatients with more than one episodes of mania |
| second group | – | Diagnostic Test: Magnetic resonance imagingsex-matched and age- matched healthy controls |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- patients diagnosed to have mood disorder Bipolar I mania with or without psychotic features according to criteria of Diagnostic and Statistical Manual of Mental disorders-IV by psychiatric sheath of psychiatric unit at Assiut University hospital . and sex and age-matched healthy subjects
Key inclusion criteria (1 listed)
- clinically diagnosed to have mood disorder Bipolar I mania with or without psychotic features according to criteria of Diagnostic and Statistical Manual of Mental disorders-IV by psychiatric sheath of psychiatric unit at Assiut University hospital .
Key exclusion criteria (4 listed)
- first and second degree relatives of psychiatric patients will be excluded from the healthy controls.
- Persons with any neurological disorder or other psychiatric illness will be excluded from controls
- Patients with proven major structural abnormality as detected during Magnetic Resonance Imaging examination will be excluded from patients or healthy controls.
- -
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 |
|---|---|---|
| Magnetic resonance imagingA full Magnetic Resonance Imaging examination of the brain will be done for each of the subjects included in the study. The protocol of the study will include a high-resolution thin-cuts three Dimensions-T1 weighted gradient echo sequence to be used for the morphometric study. The obtained images will be analyzed for any gross structural abnormalities. by using fully-automated computational voxel-based volumetric software that calculates the volume of different structures of the brain. The obtained data will be analyzed statistically using linear regression tests to determine the differences between Bipolar Disorder type I mania patients and the healthy controls | Diagnostic test | first group, second group |
Primary outcome
mean differences in measurements of different brain structures
Time frame: 2 hours
mean differences in measurements of brain structures between patients of Mania and Healthy controls by using standard of all statistical parametric brain mapping-based processing software.voxels typically represent a volume of 27 mm3 (a cube with 3mm length sides)
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 18 Jun 2020.
- Background: PubMed 26857596Hibar DP, Westlye LT, van Erp TG, Rasmussen J, Leonardo CD, Faskowitz J, Haukvik UK, Hartberg CB, Doan NT, Agartz I, Dale AM, Gruber O, Kramer B, Trost S, Liberg B, Abe C, Ekman CJ, Ingvar M, Landen M, Fears SC, Freimer NB, Bearden CE; Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes; Sprooten E, Glahn DC, Pearlson GD, Emsell L, Kenney J, Scanlon C, McDonald C, Cannon DM, Almeida J, Versace A, Caseras X, Lawrence NS, Phillips ML, Dima D, Delvecchio G, Frangou S, Satterthwaite TD, Wolf D, Houenou J, Henry C, Malt UF, Boen E, Elvsashagen T, Young AH, Lloyd AJ, Goodwin GM, Mackay CE, Bourne C, Bilderbeck A, Abramovic L, Boks MP, van Haren NE, Ophoff RA, Kahn RS, Bauer M, Pfennig A, Alda M, Hajek T, Mwangi B, Soares JC, Nickson T, Dimitrova R, Sussmann JE, Hagenaars S, Whalley HC, McIntosh AM, Thompson PM, Andreassen OA. Subcortical volumetric abnormalities in bipolar disorder. Mol Psychiatry. 2016 Dec;21(12):1710-1716. doi: 10.1038/mp.2015.227. Epub 2016 Feb 9.
- Background: PubMed 12063145Angst F, Stassen HH, Clayton PJ, Angst J. Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord. 2002 Apr;68(2-3):167-81. doi: 10.1016/s0165-0327(01)00377-9.
- Background: PubMed 12751919Tondo L, Isacsson G, Baldessarini R. Suicidal behaviour in bipolar disorder: risk and prevention. CNS Drugs. 2003;17(7):491-511. doi: 10.2165/00023210-200317070-00003.
- Background: PubMed 23734914Rocha-Rego V, Jogia J, Marquand AF, Mourao-Miranda J, Simmons A, Frangou S. Examination of the predictive value of structural magnetic resonance scans in bipolar disorder: a pattern classification approach. Psychol Med. 2014 Feb;44(3):519-32. doi: 10.1017/S0033291713001013. Epub 2013 Jun 5.
- Background: PubMed 8988799Soares JC, Mann JJ. The anatomy of mood disorders--review of structural neuroimaging studies. Biol Psychiatry. 1997 Jan 1;41(1):86-106. doi: 10.1016/s0006-3223(96)00006-6.
- Background: PubMed 8397725Lipska BK, Jaskiw GE, Weinberger DR. Postpubertal emergence of hyperresponsiveness to stress and to amphetamine after neonatal excitotoxic hippocampal damage: a potential animal model of schizophrenia. Neuropsychopharmacology. 1993 Aug;9(1):67-75. doi: 10.1038/npp.1993.44.
- Background: PubMed 1695401Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990 Jul;13(7):266-71. doi: 10.1016/0166-2236(90)90107-l.
- Individual participant dataSharing planned: No
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 Brain Voxel-based Morphometry in Mania, run by Assiut University at 1 site in Egypt.
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 1 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 18 Jun 2020. 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 Egypt. 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?
mean differences in measurements of different brain structures (time frame: 2 hours). 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 NCT03181698, which also lists 7 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 18 Jun 2020.