Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans

Sponsor

University of Minnesota (Other)

Overall Status

Recruiting

CT.gov ID

NCT04032301

Collaborator

Minneapolis Veterans Affairs Medical Center (U.S. Fed)

108

Enrollment

Location

Arms

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Experimental versus PlaceboExperimental 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 :

Sep 30, 2019

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

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 Names: 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 Names: Sodium Chloride in Water

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 Names:

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 Names:

Sodium Chloride in Water

Outcome Measures

Primary Outcome Measures

Montgomery-Asberg Depression Rating Scale (MADRS) [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.
PTSD Symptom Scale-Interview for DSM-5 (PSS-I-5) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

For the PTSD+MDD group, inclusion criteria are:

Female/Male veterans
18 to 75 years old
Meets DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features
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)]
If applicable, 6 weeks of stable antidepressants/augmenting agents
Sixth grade reading level
Ability to provide consent

For the Healthy Controls group, inclusion criteria are:

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

For the Depression-only group, inclusion criteria are:

Female/Male veterans
18 to 75 years old
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
Meets criteria for MDD, single or recurrent, moderate-severe
If applicable, 6 weeks of stable antidepressants/augmenting agents
Sixth grade reading level
Ability to provide consent

For the PTSD-only group, inclusion criteria are:

Female/Male veterans
18 to 75 years old
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)]
Does not meet DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features
If applicable, 6 weeks of stable antidepressants/augmenting agents
Sixth grade reading level
Ability to provide consent

Exclusion Criteria:

For the PTSD+MDD group, exclusion criteria are:

Inability or unwillingness to provide written informed consent
Moderate/severe cognitive impairment
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
History of moderate or severe traumatic brain injury
History of comorbid substance disorder within 1 month of screening
Prior use of ketamine as an antidepressant
Clinically unstable medical illness
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
Imminent risk of suicidal/homicidal ideation and/or behavior
Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)

For the Healthy Controls group, exclusion criteria are:

Inability or unwillingness to provide written informed consent
Moderate/severe cognitive impairment
History of any major medical or psychiatric disorders
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
History of moderate or severe traumatic brain injury
History of comorbid substance disorder within 1 month of screening
Prior use of ketamine as an antidepressant
Clinically unstable medical illness
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
Imminent risk of suicidal/homicidal ideation and/or behavior
Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)

For the Depression-only group, exclusion criteria are:

Inability or unwillingness to provide written informed consent
Moderate/severe cognitive impairment
Meet DSM-5 criteria for PTSD or subthreshold PTSD
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
History of moderate or severe traumatic brain injury
History of comorbid substance disorder within 1 month of screening
Prior use of ketamine as an antidepressant
Clinically unstable medical illness
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
Imminent risk of suicidal/homicidal ideation and/or behavior
Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)

For the PTSD-only group, exclusion criteria are:

Inability or unwillingness to provide written informed consent
Moderate/severe cognitive impairment
Meet DSM-5 criteria for a diagnosis of MDD, single or recurrent, moderate to severe
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
History of moderate or severe traumatic brain injury
History of comorbid substance disorder within 1 month of screening
Prior use of ketamine as an antidepressant
Clinically unstable medical illness
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
Imminent risk of suicidal/homicidal ideation and/or behavior
Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)