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
Intervention: ketamine
Intervention description: IV infusion of ketamine 0.5mg/kg at a rate of 40mL over 40 minutes
Intervention MeSH terms: Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 247.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Depression; Ketamine; Suicide Attempt; Suicidal Ideation; Suicidality

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18-65

          2. Physically healthy and capable of undergoing ketamine infusion

          3. Willing and able to provide informed consent

          4. Diagnosis of Major Depressive Episode (MDE) as determined by the Mini International
             Neuropsychiatric Interview (MINI) (MDD participants)

          5. Hamilton Depression Rating Scale (HAM-D) 21 score ≥ 16 (MDD participants)

          6. Suicide attempt occurred within past 2 weeks (MDD Participants with Suicide Attempt)

          7. For the time frame of the past 7 days, Columbia-Suicide Severity Rating Scale (C-SSRS)
             score ≥ 3 (MDD Participants without Suicide Attempt, with Suicidal Ideation)

          8. For the time frame of the past 7 days, C-SSRS score < 3 (MDD Participants without
             Suicide Attempt, without SUicidal Ideation)

        Exclusion Criteria:

          1. Pregnancy or lactation

          2. Post-partum state (being within 2 months of delivery or miscarriage)

          3. Homicide risk as determined by clinical interview

          4. A lifetime history of psychotic disorder

          5. Any history of dissociation or dissociative disorder

          6. Bipolar disorder

          7. Pervasive developmental disorder

          8. Cognitive disorder

          9. Cluster A personality disorder

         10. Anorexia nervosa

         11. Treatment with one of the following medications, known to affect the
             glutamate-N-methyl-D-aspartate (NMDA) receptor system (specifically: lamotrigine,
             acamprosate, memantine, riluzole, or lithium)

         12. Alcohol or drug dependence (except nicotine and caffeine) within the last month or the
             use of any hallucinogen (except cannabis), including phencyclidine in the last month

         13. Any known hypersensitivity or serious adverse effect associated with ketamine
             treatment

         14. Any clinically-significant medication condition or therapy that would preclude
             treatment with ketamine, to include: Recent myocardial infarction

         15. Unstable angina

         16. Active neoplasm in the past 6 months

         17. Immunosuppressive or corticosteroid therapy within the last month, with the following
             exceptions: any inhaled, intranasal, topical or vaginal corticosteroids are allowed.

         18. Chemotherapy

         19. Head injury of loss of consciousness in the past 6 months

         20. If the subject reports any of the following disorders:

               -  Rheumatoid arthritis

               -  Lupus erythematosus

               -  Autoimmune hepatitis

               -  Autoimmune peripheral neuropathy

               -  Autoimmune pancreatitis

               -  Behcet's disease

               -  Chrohn's disease

               -  Autoimmune glomerulonephritis

               -  Grave's disease

               -  Guillain-Barre syndrome (if active)

               -  Hashimoto's thyroiditis

               -  Autoimmune polymyositis or polymyalgia (fibromyalgia is OK)

               -  Myasthenia gravis

               -  Narcolepsy

               -  Polyarteritis nodosa

               -  Scleroderma

               -  Sjogren's syndrome

               -  Transverse myelitis

               -  Wegener's granulomatosis

               -  HIstory of seizures (only childhood febrile seizures allowed)

               -  (HIV and Hepatitis are OK if stable)

         21. Systolic blood pressure > 150 and/or diastolic blood pressure >90 at screening

         22. A Corrected QT Interval (QTc) > 480 msec as determined by an ECG