miRNAs, Suicide, and Ketamine - Plasma Exosomal microRNAs as Novel Biomarkers for Suicidality and Treatment Outcome

NCT02418195 | Completed Phase 2 Results DMC

• 2 other identifiers: F1410290071R01MH107183-01
• Study Type: interventional
• Target: 247
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Major Depressive Disorder

Keywords

Depression; Ketamine; Suicide Attempt; Suicidal Ideation; Suicidality

Outcome Measures

Primary Outcomes (1)

• Beck Scale for Suicide Ideation (BSS)

  The Beck Scale for Suicidal Ideation (BSSI) is a 21-item, self-report rating scale that measures the current intensity of specific attitudes, behaviors, and plans to commit suicide. Each item consists of 3 options graded according to intensity on a 3-point scale (0-2). Scores range from 0-42, with higher scores indicating more severe symptoms. The participant numbers below correlate to the number of usable lab samples. This is the reason for discrepancy in numbers.

  180 minutes post dose

Secondary Outcomes (8)

• Montgomery Asberg Depression Rating Scale (MADRS)

  180 minutes post dose

• Beck Depression Inventory (BDI)

  180 minutes post dose

• Beck Anxiety Inventory (BAI)

  180 minutes post dose

• Beck Hopelessness Scale (BHS)

  180 minutes post dose

• 4-item Brief Psychiatric Rating Scale (BPRS)

  180 minutes post dose

Study Arms (4)

MDD with recent Suicide Attempt

ACTIVE COMPARATOR

All subjects with Major Depressive Disorder with a recent Suicide Attempt (in the past 2 weeks) will receive a one-time IV infusion of ketamine at a dose of 0.5mg/kg at a rate of 40 milliliters (mL) over 40 minutes. Blood will be drawn at pre-dose, 30 minutes post dose, 180 minutes post dose, 24 hours post dose, and 14 days post dose to measure changes in miRNAs.

Drug: ketamine

MDD with Suicidal Ideation no attempt

ACTIVE COMPARATOR

All subjects with Major Depressive Disorder with recent Suicidal Ideation (in the past 7 days) without a recent Suicide Attempt (in the past 6 months) will receive a one-time IV infusion of ketamine at a dose of 0.5mg/kg at a rate of 40mL over 40 minutes. Blood will be drawn at pre-dose, 30 minutes post dose, 180 minutes post dose, 24 hours post dose, and 14 days post dose to measure changes in miRNAs.

Drug: ketamine

MDD without Suicidal Ideation no attempt

ACTIVE COMPARATOR

All subjects with Major Depressive Disorder without recent Suicidal Ideation (in the past 7 days) without a recent Suicide Attempt (in the past 6 months) will receive a one-time IV infusion of ketamine at a dose of 0.5mg/kg at a rate of 40mL over 40 minutes. Blood will be drawn at pre-dose, 30 minutes post dose, 180 minutes post dose, 24 hours post dose, and 14 days post dose to measure changes in miRNAs.

Drug: ketamine

Healthy Controls

NO INTERVENTION

Healthy Control subjects without a psychiatric diagnosis will have a one-time blood draw to examine miRNAs.

Interventions

ketamine DRUG

IV infusion of ketamine 0.5mg/kg at a rate of 40mL over 40 minutes

Also known as: ketalar

MDD with Suicidal Ideation no attempt; MDD with recent Suicide Attempt; MDD without Suicidal Ideation no attempt

Eligibility Criteria

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

You may qualify if:

• Age 18-65
• Physically healthy and capable of undergoing ketamine infusion
• Willing and able to provide informed consent
• Diagnosis of Major Depressive Episode (MDE) as determined by the Mini International Neuropsychiatric Interview (MINI) (MDD participants)
• Hamilton Depression Rating Scale (HAM-D) 21 score ≥ 16 (MDD participants)
• Suicide attempt occurred within past 2 weeks (MDD Participants with Suicide Attempt)
• 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)
• For the time frame of the past 7 days, C-SSRS score \< 3 (MDD Participants without Suicide Attempt, without SUicidal Ideation)

You may not qualify if:

• Pregnancy or lactation
• Post-partum state (being within 2 months of delivery or miscarriage)
• Homicide risk as determined by clinical interview
• A lifetime history of psychotic disorder
• Any history of dissociation or dissociative disorder
• Bipolar disorder
• Pervasive developmental disorder
• Cognitive disorder
• Cluster A personality disorder
• Anorexia nervosa
• 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)
• 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
• Any known hypersensitivity or serious adverse effect associated with ketamine treatment
• Any clinically-significant medication condition or therapy that would preclude treatment with ketamine, to include: Recent myocardial infarction
• Unstable angina

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Suicide, Attempted; Suicidal Ideation

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Suicide; Self-Injurious Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Samantha White/ Clinical Trials Manager
• Organization: University of Alabama at Birmingham

swwhite@uabmc.edu

12059349189

Study Officials

• Yogesh Dwivedi, Ph.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Richard C Shelton, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 13, 2015
• First Posted: April 16, 2015
• Study Start: April 20, 2015
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: August 30, 2022
• Results First Posted: July 5, 2022

Record last verified: 2022-08

Locations

US (1)