Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06439797
Status:
COMPLETED
Last Update Posted:
2024-06-03
First Post:
2024-05-28
Brief Title:
Inflammatory Markers as Predictors of the Efficacy of Electroconvulsive Therapy ECT in Major Depression Patients
Sponsor:
The Chaim Sheba Medical Center
Organization:
The Chaim Sheba Medical Center
Study Overview
Official Title:
Inflammatory Markers as Predictors of the Efficacy of Electroconvulsive Therapy ECT in Major Depression Patients
Status:
COMPLETED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ECT MDD
Brief Summary:
Background ECT is an effective treatment indicated for patients with treatment resistant depression Although most patients display some degree of recovery 32-52 do not respond or remit at all Considering the possible side effects and the considerably high cost of treatment it is important to identify sub-populations that would benefit the most from ECT In the current study we sought to identify predictive molecular markers in the blood of depressed patients who are responsive to ECT
Methods Patients ages 18-70 with the diagnosis of treatment-resistant depression will be recruited Participants will undergo psychiatric and psychological assessments before baseline and 12 weeks after ECT initiation Assessments will include the Montgomery-Asberg Depression Rating Scale MADRAS Clinical Global Improvement and Severity Scales CGI-S CGI-I Inventory of Depressive Symptomatology IDS and the State-Trait Anxiety Inventory STAI Blood samples for serum and isolation of peripheral blood mononuclear cells PBMCswill be collected at baseline and the 12-week end-of-treatment time points for molecular analysis
Methods Patients ages 18-70 with the diagnosis of treatment-resistant depression will be recruited Participants will undergo psychiatric and psychological assessments before baseline and 12 weeks after ECT initiation Assessments will include the Montgomery-Asberg Depression Rating Scale MADRAS Clinical Global Improvement and Severity Scales CGI-S CGI-I Inventory of Depressive Symptomatology IDS and the State-Trait Anxiety Inventory STAI Blood samples for serum and isolation of peripheral blood mononuclear cells PBMCswill be collected at baseline and the 12-week end-of-treatment time points for molecular analysis
Detailed Description:
Despite impressive progress in our understanding of the molecular cellular and circuit-level correlates of major depression the biological mechanisms that causally underlie this disorder remain unclear hindering the development of effective novel therapeutic procedures One possible reason for this situation is that almost all research in this area focuses on the involvement of abnormalities in neuronal functioning whereas the involvement of non-neuronal brain cells particularly microglia has not been thoroughly investigated Recent studies indicate that impairments of the normal structure and function of microglia caused by either intense inflammatory activation or by decline and senescence of these cells can lead to depression and associated impairments in neuroplasticity and neurogenesis Accordingly we argued that at least some forms of depression can be considered as microgliopathies in which either microglial activation or microglial decline and suppression constitute the direct etiology of the depressive syndrome This implies that depression cannot be treated uniformly but should rather be treated by a personalized medical approach based on the microglial status of the individual depressed patient Yirmiya et al TiNS 2015 In the current proposal we aim to lay foundations for a thorough examination of the personalized medical approach to depression by examining the benefits of personalized utilization of anti-depressive procedures based on screening for inflammatory microglial markers and by developing state-of-the-art tools for microglia manipulations that will allow to directly examine the causal role of these cells in various animal models of depression
We specifically aim to develop a personalized approach to the utilization of electroconvulsive therapy ECT because our preliminary findings in a mouse model of depression associated with impaired microglia functioning conclusively show that ECT-induced microglia activation is causally related to the anti-depressive effects of this treatment We propose to utilize a translational approach assessing the inflammatorymicroglia-related molecular factors measured before treatment that predict and contribute to the efficacy of ECT in major depression patients Specifically we expect that ECT will be more beneficial in patients with low expression of inflammatorymicroglia-related genes and thus based on the findings of this experiment we shall be able to devise a molecular screening for the suitability of ECT and possibly other anti-depressant procedures for the individual depressed patient Furthermore we aim to establish the transcriptomic effects of ECT with a particular emphasis on inflammatory-related pathways We expect differential transcriptomic effects of ECT in patients with high vs low baseline inflammatory status The results should significantly contribute to our knowledge regarding the molecular mechanisms that underlie the therapeutic effects of ECT in specific sub-groups of depressed patients
In parallel studies we aim to develop molecular tools for selective and region-specific microglia activation or inhibition and to use these tools for 1 examining the effects of these manipulations in animal models of depression that involve either hyper-or hypo-activity of microglia 2 defining the causal role of microglia in mediating the anti-depressive effects of ECT in a depression model associated with low microglia status These studies should complement the clinical part in humans by providing definitive evidence for the inverted U-shape pattern of relations between inflammatory status and depression which constitutes the basis for the personalized medical approach to this disease
We specifically aim to develop a personalized approach to the utilization of electroconvulsive therapy ECT because our preliminary findings in a mouse model of depression associated with impaired microglia functioning conclusively show that ECT-induced microglia activation is causally related to the anti-depressive effects of this treatment We propose to utilize a translational approach assessing the inflammatorymicroglia-related molecular factors measured before treatment that predict and contribute to the efficacy of ECT in major depression patients Specifically we expect that ECT will be more beneficial in patients with low expression of inflammatorymicroglia-related genes and thus based on the findings of this experiment we shall be able to devise a molecular screening for the suitability of ECT and possibly other anti-depressant procedures for the individual depressed patient Furthermore we aim to establish the transcriptomic effects of ECT with a particular emphasis on inflammatory-related pathways We expect differential transcriptomic effects of ECT in patients with high vs low baseline inflammatory status The results should significantly contribute to our knowledge regarding the molecular mechanisms that underlie the therapeutic effects of ECT in specific sub-groups of depressed patients
In parallel studies we aim to develop molecular tools for selective and region-specific microglia activation or inhibition and to use these tools for 1 examining the effects of these manipulations in animal models of depression that involve either hyper-or hypo-activity of microglia 2 defining the causal role of microglia in mediating the anti-depressive effects of ECT in a depression model associated with low microglia status These studies should complement the clinical part in humans by providing definitive evidence for the inverted U-shape pattern of relations between inflammatory status and depression which constitutes the basis for the personalized medical approach to this disease
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None