miRNAs, Suicide, and Ketamine - Plasma Exosomal microRNAs as Novel Biomarkers for Suicidality and Treatment Outcome
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major; Suicidal Ideation
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to examine whether neural-derived exosomal miRNAs are
      differentially expressed that are specific to suicidal ideation or behavior, and which by
      affecting specific miRNA targets and pathways, are associated with suicidal behavior and
      response to ketamine. The following groups of subjects will be examined: 1) major depressive
      disorder (MDD) with a recent suicide attempt (in past 2 weeks), 2) MDD with serious ideation
      (in the past 7 days) without recent suicide attempt (in the past 6 months), 3) MDD without
      clinically significant suicidal ideation (in the past 7 days) or recent suicide attempt (in
      the past 6 months), and 4) healthy controls. Both suicidal and non-suicidal MDD will be given
      ketamine (0.5 mg/kg, IV) and blood will be drawn at predose, 30 min, 180 min, 24 hours, and
      14 days post-infusion to measure changes in miRNAs.

      As of May 2022, study is in data analysis. Final outcomes will be known once analysis is
      complete.

      As of July 2022, all data collection is complete. The primary and secondary data outcome
      measure results are complete.

      The investigators are working on final analysis of the mRNA samples, to provide final
      responses to questions posed in the Detailed Description section below and listed here: 1)
      whether suicidal ideation or behavior is associated with differences in the expression of
      specific miRNAs, 2) whether anti-suicidal/antidepressant effects of ketamine is associated
      with miRNAs changes, and 3) whether miRNA/mRNA-regulatory pathways contribute to suicide
      pathogenesis and treatment response.
    

Detailed description: 
      Neural MicroRNAs (miRNAs) are responsive to environmental, synaptic, and pathological changes
      and can be actively secreted by cells such as exosomes from brain into blood. These exosomes
      bear cell-type specific surface markers. Using a neural specific surface marker, the
      investigators successfully isolated neural-derived exosomes and found that these exosomes are
      enriched with miRNAs/Messenger RNA (mRNAs) that are expressed in brain. Using this novel
      approach the investigators aim to examine whether neural derived exosomal miRNAs are
      differentially expressed that are specific to suicidal ideation or behavior, and which by
      affecting specific mRNA targets and pathways, are associated with suicidal behavior and
      response to ketamine.

      The following groups of subjects will be examined: 1) major depressive disorder (MDD) with a
      recent suicide attempt (in past 2 weeks), 2) MDD with serious ideation (in the past 7 days)
      without recent suicide attempt (in the past 6 months), 3) MDD without clinically significant
      suicidal ideation (in the past 7 days) or suicide attempt in the past 6 months, and 4)
      healthy controls. Both suicidal and non-suicidal MDD will be given ketamine (0.5 mg/kg, IV)
      and blood will be drawn at pre-infusion, 30 minutes and 180 minutes post-infusion to measure
      changes in miRNAs. Healthy controls will have a one-time blood draw. The investigators also
      propose a parallel human postmortem brain study to examine whether changes in miRNAs in
      suicidality correspond to miRNA changes in brain by comparing dlPFC and hippocampus from MDD
      suicide, MDD non-suicide, and control subjects.

      With this the investigators attempt to discover 1) whether suicidal ideation or behavior is
      associated with differences in the expression of specific miRNAs, 2) whether
      anti-suicidal/antidepressant effects of ketamine is associated with miRNAs changes, and 3)
      whether miRNA/mRNA-regulatory pathways contribute to suicide pathogenesis and treatment
      response. Our study will provide a novel avenue for the development of miRNAs as ''molecular
      tool'' to identify suicidality and treatment response and in generating target based
      therapies to treat this devastating disorder.
    

Intervention name(s): ketamine
Intervention type(s): Drug
Intervention description(s): IV infusion of ketamine 0.5mg/kg at a rate of 40mL over 40 minutes
Other intervention name(s): ketalar
Intervention MeSH terms: Ketamine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Depression; Ketamine; Suicide Attempt; Suicidal Ideation; Suicidality