Ignite Creation Date:
2024-05-06 @ 7:04 PM
Last Modification Date:
2024-10-26 @ 3:00 PM
Study NCT ID:
NCT05887310
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2023-06-02
First Post:
2023-05-24
Brief Title:
In Vitro Modeling of Drug-resistant Psychiatric Disorders Using Induced Pluripotent Cells
Sponsor:
University of Milano Bicocca
Organization:
University of Milano Bicocca
Study Overview
Official Title:
In Vitro Modeling of Drug-resistant Psychiatric Disorders Using Induced Pluripotent Cells
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2023-05
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:
None
Brief Summary:
Major depressive disorder MDD is a major medical and economic burden for todays society About 30 of MDD patients develop treatment-resistant depression - TRD with the related sequelae in terms of worse prognosis
If several risk factors can be assessed readily on presentation it can guide treatment planning and ultimately improve clinical outcomes Currently unlike other areas of medicine poly-risk tools to facilitate this stratification in practice among patients with MDD are lacking but demanded in the era of personalisedprecision medicine - a challenge that the project takes up Ketamine - a glutamate N-methyl-d-aspartate NMDA receptor antagonist is the first exemplary agent with rapid within hours antidepressant effects even in TRD patientsIts mechanisms of actions MoA are still unclear but greatly demanded
So far insights about ketamines MoA come from preclinical animal studies but its known that animal models have limited abilityeffectiveness in mimicking the clinical complexity and were not subjected to sequential application of different treatments - a key requisite in humans to be defined as TRD This ambitious intermultidisciplinary project has 3 goals
1 To develop a clinical risk stratification tool for predicting TRD development
2 To unravel ketamines fast-acting antidepressant mechanisms of action MoA on mature neurons obtained from human induced pluripotent stem cells iPSCs obtained from ketamine-responsive non-responsive patients with TRD
3 To give maximum visibility to the project and spreading its contents findings to and in a way understood by all target groups variously implicatedinterested in project research innovation
If several risk factors can be assessed readily on presentation it can guide treatment planning and ultimately improve clinical outcomes Currently unlike other areas of medicine poly-risk tools to facilitate this stratification in practice among patients with MDD are lacking but demanded in the era of personalisedprecision medicine - a challenge that the project takes up Ketamine - a glutamate N-methyl-d-aspartate NMDA receptor antagonist is the first exemplary agent with rapid within hours antidepressant effects even in TRD patientsIts mechanisms of actions MoA are still unclear but greatly demanded
So far insights about ketamines MoA come from preclinical animal studies but its known that animal models have limited abilityeffectiveness in mimicking the clinical complexity and were not subjected to sequential application of different treatments - a key requisite in humans to be defined as TRD This ambitious intermultidisciplinary project has 3 goals
1 To develop a clinical risk stratification tool for predicting TRD development
2 To unravel ketamines fast-acting antidepressant mechanisms of action MoA on mature neurons obtained from human induced pluripotent stem cells iPSCs obtained from ketamine-responsive non-responsive patients with TRD
3 To give maximum visibility to the project and spreading its contents findings to and in a way understood by all target groups variously implicatedinterested in project research innovation
Detailed Description:
Major depressive disorder MDD affecting roughly 300 million people is a major medical and economic burden for todays society Unsatisfactory response to current antidepressants contributes to the enormous public health burden of MDD Critically about 30 of MDD patients develop treatment-resistant depression - TRD ie do not respond adequately to at least 2 successive antidepressant treatments under a proper therapeutic regimen with the related sequelae in terms of worse prognosis When an outpatient first presents for treatment of MDD what is the likelihood that she will not reach symptomatic remission despite multiple treatment trials If several risk factors can be assessed readily on presentation it can guide treatment planning and ultimately improve clinical outcomes Human genome-wide association studies have failed to identify common variants associated with TRD Large-scale studies have pointed toward strong effects of clinical variables on treatment outcome yet considered separately clinical variables usually showed odds ratios around 15 and thus were not applicable for stratifying MDD patients and detecting those at high risk On the other hand compelling evidence supports the consideration of measuring peripheral biomarkers that could result in improved stratification and TRD prediction Currently unlike other areas of medicine poly-risk tools to facilitate this stratification in practice among patients with MDD are lacking but demanded in the era of personalisedprecision medicine - a challenge that the project takes up Treatments that exert fast-acting antidepressant action are an unmet clinical need as the effects of currently available medications often take several weeks to promote clinical response if MDD patients show a response Ketamine - a glutamate N-methyl-d-aspartate NMDA receptor antagonist is the first exemplary agent with rapid within hours antidepressant effects even in TRD patients Multiple controlled trials demonstrate that 50-70 of TRD patients show clinical response after a single dose of ketamine delivered intravenously for 40 minutes Although ketamine seems poised to transform the treatment of depression its mechanisms of actions MoA are still unclear but greatly demanded as the derived knowledge can provide a model for understanding the mechanisms behind rapidly acting antidepressants which may lead to the discovery of novel compounds to treat depression So far insights about ketamines MoA come from preclinical animal studies which underscored complex pathways involvement and possible changes in synaptic structural plasticity However animal models have limited abilityeffectiveness in mimicking the clinical complexity and were not subjected to sequential application of different treatments - a key requisite in humans to be defined as TRD According to the American Psychiatric Association Council of Research Task Force on Novel Biomarkers and Treatments although ketamines antidepressant efficacy is promising for future glutamate-modulating strategies the fact that other NMDA antagonists do not have antidepressant proprieties suggests that any forthcoming advances will depend on improving our understanding of ketamines MoA hopefully in humans - a challenge that the project takes up This ambitious intermultidisciplinary project going beyond the state-of-the-art embracing responsible research innovation principles and involving training and professional opportunities for young researchers has 3 goals
1 To develop a clinical risk stratification tool for predicting TRD development Specifically well implement machine learning a form of artificial intelligence to evaluate the prognostic value of 55 socio-demographic clinical variables including comorbid anxiety disorders and peripheral biomarkers to establish a predictive clinical risk stratification tool for TRD
2 To unravel ketamines fast-acting antidepressant mechanisms of action MoA on mature neurons obtained from human induced pluripotent stem cells iPSCs obtained from ketamine-responsive non-responsive patients with TRD Here well capitalize on iPSC technology and the distinctive paradigm of rapid mood normalization following ketamine infusion to disclose mechanisms of action accounting for fast-acting antidepressant effect on patient-derived differentiated neurons Well explore whether the changes and complex pathways observed in animal models can be validated in patients and potentially identity new ones
3 To give maximum visibility to the project and spreading its contents findings to and in a way understood by all target groups variously implicatedinterested in project research innovation A series of public engagement initiatives will also foster communication and interaction between researchers civil society making real research and its process more concrete simple accessible and closer to society and contributing to citizen science
1 To develop a clinical risk stratification tool for predicting TRD development Specifically well implement machine learning a form of artificial intelligence to evaluate the prognostic value of 55 socio-demographic clinical variables including comorbid anxiety disorders and peripheral biomarkers to establish a predictive clinical risk stratification tool for TRD
2 To unravel ketamines fast-acting antidepressant mechanisms of action MoA on mature neurons obtained from human induced pluripotent stem cells iPSCs obtained from ketamine-responsive non-responsive patients with TRD Here well capitalize on iPSC technology and the distinctive paradigm of rapid mood normalization following ketamine infusion to disclose mechanisms of action accounting for fast-acting antidepressant effect on patient-derived differentiated neurons Well explore whether the changes and complex pathways observed in animal models can be validated in patients and potentially identity new ones
3 To give maximum visibility to the project and spreading its contents findings to and in a way understood by all target groups variously implicatedinterested in project research innovation A series of public engagement initiatives will also foster communication and interaction between researchers civil society making real research and its process more concrete simple accessible and closer to society and contributing to citizen science
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?:
False
Is an FDA AA801 Violation?:
None