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Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans

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ClinicalTrials.gov Identifier: NCT04032301
Recruitment Status : Recruiting
First Posted : July 25, 2019
Last Update Posted : October 3, 2019
Sponsor:
Collaborator:
Minneapolis Veterans Affairs Medical Center
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

Brief Summary:
Co-occurring post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) is the most common response to trauma; it is associated with poor clinical outcomes and substantial human disability. Veterans with both PTSD and MDD (PTSD+MDD) have been shown to be at much greater suicidal risk than individuals with only one of these disorders. Ketamine given as repeated infusions has been shown to be effective in rapidly reducing PTSD and MDD symptoms in treatment resistant PTSD+MDD individuals. However, knowledge about the mechanisms underlying comorbid PTSD and MDD remain limited. The purpose of this study is to use repeated ketamine infusions as a probe to validate a model of PTSD+MDD that focuses on neuroanatomy and executive functioning.

Condition or disease Intervention/treatment Phase
Post-Traumatic Stress Disorders Major Depressive Disorder Drug: Ketamine Other: Normal Saline Phase 1

Detailed Description:
This study is designed to better characterize the neurocognitive and associated functional connectivity mechanisms underlying comorbid post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) among veterans. Participants will be male/female veterans (18 to 75 years old) of any era or military background who suffer from chronic PTSD and MDD. Potential participants will be recruited from mental health clinics and screened for eligibility using a two stage process (phone/chart review, followed by interview). Participants with PTSD+MDD will undergo a series of baseline assessments including a baseline functional magnetic resonance imaging (fMRI) then be randomized to receive either 6 ketamine or 6 normal saline infusions on a Monday-Friday schedule over 3 weeks. On the day of infusion, participants will be required to stay at the clinical site for 2 hours after the infusion has been given. They will also be monitored via a phone call on the following day. After the infusion period has been completed participants will undergo a follow-up fMRI then 4 follow-up visits, up to 2 months. Additional participants will be enrolled in healthy control, depression only, and PTSD only groups and will only undergo baseline assessments, including a single fMRI.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Experimental versus Placebo
Masking: Double (Participant, Investigator)
Primary Purpose: Diagnostic
Official Title: Characterization of Comorbid Post-traumatic Stress Disorder and Major Depressive Disorder Utilizing Ketamine as an Experimental Medicine Probe
Actual Study Start Date : September 30, 2019
Estimated Primary Completion Date : September 1, 2024
Estimated Study Completion Date : September 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intravenous ketamine infusions
Six infusions of 0.5 mg/kg ketamine hydrochloride solution over 3 weeks.
Drug: Ketamine
Six infusions of intravenous 0.5 mg/kg ketamine hydrochloride solution over 3 weeks.
Other Name: Ketamine Hydrochloride

Placebo Comparator: Intravenous saline infusions
Six infusions of normal saline solution over 3 weeks.
Other: Normal Saline
Six infusions of intravenous normal saline solution over 3 weeks.
Other Name: Sodium Chloride in Water




Primary Outcome Measures :
  1. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: At baseline, 60 minutes pre-infusion, 24 hours post-infusion, and after infusion series up to 2 months. ]
    Change in major depressive disorder symptoms over the course of the intervention.

  2. PTSD Symptom Scale-Interview for DSM-5 (PSS-I-5) [ Time Frame: At baseline, 60 minutes pre-infusion, 24 hours post-infusion, and after infusion series up to 2 months. ]
    Change in post-traumatic stress disorder symptoms over the course of the intervention.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

For the PTSD+MDD group, inclusion criteria are:

  1. Female/Male veterans
  2. 18 to 75 years old
  3. Meets DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features
  4. Meets DSM-5 criteria for chronic PTSD or subthreshold PTSD [meets criterion A (traumatic event), criterion B (intrusion symptoms), and 2 of the following 3 criteria: C (avoidance symptoms), D (negative alterations in cognitions and mood), or E (marked alterations in arousal and reactivity)]
  5. If applicable, 6 weeks of stable antidepressants/augmenting agents
  6. Sixth grade reading level
  7. Ability to provide consent

For the Healthy Controls group, inclusion criteria are:

  1. Female/Male veterans
  2. 18 to 75 years old
  3. Does not meet DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features
  4. Does not meet DSM-5 criteria for chronic PTSD or subthreshold PTSD
  5. Not on medications for managing a psychiatric indication
  6. Sixth grade reading level
  7. Ability to provide consent

For the Depression-only group, inclusion criteria are:

  1. Female/Male veterans
  2. 18 to 75 years old
  3. Experienced a traumatic event that meets DSM-5 criterion A for a diagnosis of PTSD but does not meet sufficient criteria (B-E) necessary for a diagnosis of PTSD or subthreshold PTSD
  4. Meets criteria for MDD, single or recurrent, moderate-severe
  5. If applicable, 6 weeks of stable antidepressants/augmenting agents
  6. Sixth grade reading level
  7. Ability to provide consent

For the PTSD-only group, inclusion criteria are:

  1. Female/Male veterans
  2. 18 to 75 years old
  3. Meets DSM-5 criteria for chronic PTSD or subthreshold PTSD [meets criterion A (traumatic event), criterion B (intrusion symptoms), and 2 of the following 3 criteria: C (avoidance symptoms), D (negative alterations in cognitions and mood), or E (marked alterations in arousal and reactivity)]
  4. Does not meet DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features
  5. If applicable, 6 weeks of stable antidepressants/augmenting agents
  6. Sixth grade reading level
  7. Ability to provide consent

Exclusion Criteria:

For the PTSD+MDD group, exclusion criteria are:

  1. Inability or unwillingness to provide written informed consent
  2. Moderate/severe cognitive impairment
  3. Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition
  4. History of moderate or severe traumatic brain injury
  5. History of comorbid substance disorder within 1 month of screening
  6. Prior use of ketamine as an antidepressant
  7. Clinically unstable medical illness
  8. For women: pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study
  9. Imminent risk of suicidal/homicidal ideation and/or behavior
  10. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)

For the Healthy Controls group, exclusion criteria are:

  1. Inability or unwillingness to provide written informed consent
  2. Moderate/severe cognitive impairment
  3. History of any major medical or psychiatric disorders
  4. Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition
  5. History of moderate or severe traumatic brain injury
  6. History of comorbid substance disorder within 1 month of screening
  7. Prior use of ketamine as an antidepressant
  8. Clinically unstable medical illness
  9. For women: pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study
  10. Imminent risk of suicidal/homicidal ideation and/or behavior
  11. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)

For the Depression-only group, exclusion criteria are:

  1. Inability or unwillingness to provide written informed consent
  2. Moderate/severe cognitive impairment
  3. Meet DSM-5 criteria for PTSD or subthreshold PTSD
  4. Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition
  5. History of moderate or severe traumatic brain injury
  6. History of comorbid substance disorder within 1 month of screening
  7. Prior use of ketamine as an antidepressant
  8. Clinically unstable medical illness
  9. For women: pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study
  10. Imminent risk of suicidal/homicidal ideation and/or behavior
  11. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)

For the PTSD-only group, exclusion criteria are:

  1. Inability or unwillingness to provide written informed consent
  2. Moderate/severe cognitive impairment
  3. Meet DSM-5 criteria for a diagnosis of MDD, single or recurrent, moderate to severe
  4. Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition
  5. History of moderate or severe traumatic brain injury
  6. History of comorbid substance disorder within 1 month of screening
  7. Prior use of ketamine as an antidepressant
  8. Clinically unstable medical illness
  9. For women: pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study
  10. Imminent risk of suicidal/homicidal ideation and/or behavior
  11. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)

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): NCT04032301


Contacts
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Contact: Sey Lee, BS 612-629-7489 Sey.Lee@va.gov
Contact: Christina S Albott, MD, MA 612-273-9041 Cristina.Albott@va.gov

Locations
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United States, Minnesota
Minneapolis Veterans Affairs Health Care System Recruiting
Minneapolis, Minnesota, United States, 55417
Contact: Sey Lee, BS         
Principal Investigator: Christina S Albott, MD, MA         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Minneapolis Veterans Affairs Medical Center
Investigators
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Principal Investigator: Christina S Albott, MD, MA Minneapolis Veterans Affairs Medical Center

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Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT04032301     History of Changes
Other Study ID Numbers: VAM-18-00364
First Posted: July 25, 2019    Key Record Dates
Last Update Posted: October 3, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
ketamine
stress disorders, post-traumatic
stress disorders, traumatic
anxiety disorders
mental disorders
adjuvants, anesthesia
analgesics
anesthetics
anesthetics, dissociative
anesthetics, general
anesthetics, intravenous
excitatory amino acid agents
excitatory amino acid antagonists
hypnotics and sedatives
molecular mechanisms of pharmacological action
neurotransmitter agents
peripheral nervous system agents
pharmacologic actions
physiological effects of drugs
psychotropic drugs
sensory system agents
central nervous system agents
central nervous system depressants
depression
depressive disorder
depressive disorder, treatment-resistant
behavioral symptoms
mood disorders
therapeutic uses
Additional relevant MeSH terms:
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Ketamine
Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Trauma and Stressor Related Disorders
Anesthetics
Pharmaceutical Solutions
Excitatory Amino Acids
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action