In Vitro Modeling of Drug-resistant Psychiatric Disorders Using Induced Pluripotent Cells

NCT05887310 | Unknown

• 1 other identifier: FaReStem
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder (MDD), is a major medical and economic burden for today's 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 personalised/precision 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 patients.Its mechanisms of actions (MoA) are still unclear but greatly demanded. So far, insights about ketamine's MoA come from preclinical animal studies but it's known that animal models have limited ability/effectiveness 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 inter/multidisciplinary project, has 3 goals:

1. 1.To develop a clinical risk stratification tool for predicting TRD development.
2. 2.To unravel ketamine's 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. 3.To give maximum visibility to the project and spreading its contents \& findings to and in a way understood by all target groups variously implicated/interested in project research \& innovation.

Conditions

Depressive Disorder, Treatment-Resistant

Keywords

Ketamine; Esketamine; induced Pluripotent Stem Cells

Outcome Measures

Primary Outcomes (1)

• Create in vitro human cellular models of some drug-resistant psychiatric disorders.

  Using cellular reprogramming techniques, create in vitro human cellular models of the following drug-resistant psychiatric disorders: * Disorders of the schizophrenic spectrum; * Bipolar spectrum disorders; * Depressive disorders; * Obsessive-compulsive disorders; * Anxiety disorders.

  Entire study duration (approximately 10 years)

Secondary Outcomes (1)

• To study the etiopathogenesis of these drug-resistant psychiatric disorders

  Entire study duration (approximately 10 years)

Study Arms (1)

Patients with drug-resistant psychiatric disorders

Eligibility Criteria

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

Study Population

Patients with drug-resistant psychiatric disorders.

You may qualify if:

• Age ≥ 18 years;
• Diagnosis, confirmed through the Structured Clinical Interview for DSM-5, of:
• Schizophrenic spectrum disorder;
• Bipolar spectrum disorder;
• Depressive Disorder
• Obsessive-Compulsive Disorder
• Anxiety Disorder;
• Clear evidence of drug resistance (defined, according to the EMA criteria and the literature, as failure at a minimum of 2 treatments set for adequate dosage and duration);
• Informed consent freely granted and acquired before the start of the study

You may not qualify if:

• Age ≥ 80 years;
• History of drug abuse;
• Comorbidity with neurodegenerative neurological disorders;
• Diagnosis of Intellectual Disability

Sponsors & Collaborators

• University of Milano Bicocca: lead
• Università degli Studi di Trento: collaborator
• National Research Council: collaborator

Study Sites (1)

Fondazione IRCCS San Gerardo di Monza

Monza, Monza E Brianza, 20900, Italy

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2023
• First Posted: June 2, 2023
• Study Start: August 5, 2022
• Primary Completion: August 5, 2024
• Study Completion: August 5, 2024
• Last Updated: June 2, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)