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Trial record 48 of 419 for:    depression OR mood disorders OR depressive disorder OR bipolar depression OR postpartum depression OR child depression OR adolescent depression OR geriatric depression OR psychotic depression OR anhedonia OR dysphoria OR minor depression | Recruiting, Not yet recruiting, Available Studies | NIH

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

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ClinicalTrials.gov Identifier: NCT02418195
Recruitment Status : Recruiting
First Posted : April 16, 2015
Last Update Posted : August 3, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Yogesh Dwivedi, PhD, University of Alabama at Birmingham

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.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: ketamine Phase 2

Detailed Description:

Neural 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/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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Plasma Exosomal MicroRNAs as Promising Novel Biomarkers for Suicidality and Treatment Outcome
Study Start Date : April 2015
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Suicide
Drug Information available for: Ketamine

Arm Intervention/treatment
Active Comparator: MDD with recent Suicide Attempt
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 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
IV infusion of ketamine 0.5mg/kg at a rate of 40mL over 40 minutes
Other Name: ketalar

Active Comparator: MDD with Suicidal Ideation no attempt
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
IV infusion of ketamine 0.5mg/kg at a rate of 40mL over 40 minutes
Other Name: ketalar

Active Comparator: MDD without Suicidal Ideation no attempt
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
IV infusion of ketamine 0.5mg/kg at a rate of 40mL over 40 minutes
Other Name: ketalar

No Intervention: Healthy Controls
Healthy Control subjects without a psychiatric diagnosis will have a one-time blood draw to examine miRNAs.



Primary Outcome Measures :
  1. Beck Scale for Suicide Ideation (BSS) [ Time Frame: 180 minutes post dose ]

Secondary Outcome Measures :
  1. Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: 180 minutes post dose ]
  2. Beck Depression Inventory (BDI) [ Time Frame: 180 minutes post dose ]
  3. Beck Anxiety Inventory (BAI) [ Time Frame: 180 minutes post dose ]
  4. Beck Hopelessness Scale (BHS) [ Time Frame: 180 minutes post dose ]
  5. 4-item Brief Psychiatric Rating Scale (BPRS) [ Time Frame: 180 minutes post dose ]
  6. Clinician-Administered Dissociative States Scale (CADSS) [ Time Frame: 180 minutes post dose ]
  7. Young Mania Rating Scale (YMRS) [ Time Frame: 180 minutes post dose ]
  8. Systematic Assessment for Treatment Emergent Events (SAFTEE) [ Time Frame: 180 minutes post dose ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 MDE as determined by the MINI (MDD participants)
  5. 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, 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-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 QTc > 480 msec as determined by an ECG

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02418195


Contacts
Contact: Samantha White, BS, CCRC 205-934-9189 swwhite@uabmc.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Samantha White, BS, CCRC    205-934-9189    swwhite@uabmc.edu   
Principal Investigator: Yogesh Dwivedi, PhD         
Principal Investigator: Richard C Shelton, MD         
Sponsors and Collaborators
University of Alabama at Birmingham
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Yogesh Dwivedi, Ph.D. University of Alabama at Birmingham
Principal Investigator: Richard C Shelton, M.D. University of Alabama at Birmingham

Responsible Party: Yogesh Dwivedi, PhD, Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT02418195     History of Changes
Other Study ID Numbers: F141029007
1R01MH107183-01 ( U.S. NIH Grant/Contract )
First Posted: April 16, 2015    Key Record Dates
Last Update Posted: August 3, 2018
Last Verified: August 2018

Keywords provided by Yogesh Dwivedi, PhD, University of Alabama at Birmingham:
Depression
Ketamine
Suicide Attempt
Suicidal Ideation
Suicidality

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action