Post-Traumatic Stress DisordersPhase 1NCT04032301
Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans
A Phase 1 study testing Ketamine and Normal Saline in people with Post-Traumatic Stress Disorders and Major Depressive Disorder, run by University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Post-Traumatic Stress Disorders, Major Depressive Disorder
- What is being tested?
- Ketamine and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2019to 10 Nov 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.)
Trial locations and contacts
1 site in 1 country.
United States1 site
Minneapolis Veterans Affairs Health Care System
Minneapolis, Minnesota, 55417
About this study
Official title: Characterization of Comorbid Post-traumatic Stress Disorder and Major Depressive Disorder Utilizing Ketamine as an Experimental Medicine Probe
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.
Read the 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.
- Being tested
- Ketamine, Normal Saline
- Keywords
- 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
- Medical subject headings
- Stress Disorders, Post-Traumatic, Depressive Disorder, Major, Stress Disorders, Traumatic, Anxiety Disorders, Mental Disorders, Depression, Depressive Disorder, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketamine Hydrochloride
Six infusions of intravenous 0.5 mg/kg ketamine hydrochloride solution over 3 weeks.
Normal SalineOther
Also called Sodium Chloride in Water
Six infusions of intravenous normal saline solution over 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous ketamine infusions | Experimental | Six infusions of 0.5 mg/kg ketamine hydrochloride solution over 3 weeks. Receives: Drug: Ketamine |
| Intravenous saline infusions | Placebo comparator | Six infusions of normal saline solution over 3 weeks. Receives: Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale (MADRS)
Change in major depressive disorder symptoms over the course of the intervention.
Measured: At baseline, 60 minutes pre-infusion, 24 hours post-infusion, and after infusion series up to 2 months.
PTSD Symptom Scale-Interview for DSM-5 (PSS-I-5)
Change in post-traumatic stress disorder symptoms over the course of the intervention.
Measured: At baseline, 60 minutes pre-infusion, 24 hours post-infusion, and after infusion series up to 2 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2019
- Study start30 Sep 2019
- Primary completion16 Sep 2024
- Study completion10 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-Traumatic Stress DisordersStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Experimental versus Placebo
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Minneapolis Veterans Affairs Medical Center
- Responsible party
- Sponsor
- Investigators
- Cristina S Albott, MD, MA, Principal investigator, Minneapolis Veterans Affairs Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04032301
- Sponsor's protocol ID
- PSYCH-2019-28086
- Status last verified
- Jun 2025
- First submitted
- 26 Jun 2019
- Last updated
- 27 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Comorbid Post-traumatic Stress Disorder and Major Depressive Disorder Utilizing Ketamine as an Experimental Medicine Probe
- ClinicalTrials.gov ID
- NCT04032301
- Acronym / sponsor ID
- PSYCH-2019-28086
- Keywords
- ketamine, stress disorders, post-traumatic, stress disorders, traumatic, anxiety disorders, mental disorders, adjuvants, anesthesia, analgesics, anesthetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Minneapolis Veterans Affairs Medical Center
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 16 Sep 2024 (actual)
- Study completion
- 10 Nov 2024 (actual)
- First posted
- 25 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Experimental versus Placebo
| Arm | Type | Receives |
|---|---|---|
| Intravenous ketamine infusions | Experimental | Drug: KetamineSix infusions of 0.5 mg/kg ketamine hydrochloride solution over 3 weeks. |
| Intravenous saline infusions | Placebo comparator | Other: Normal SalineSix infusions of normal saline solution over 3 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- 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
Key exclusion criteria (47 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: Ketamine HydrochlorideSix infusions of intravenous 0.5 mg/kg ketamine hydrochloride solution over 3 weeks. | Drug | Intravenous ketamine infusions |
| Normal SalineAlso: Sodium Chloride in WaterSix infusions of intravenous normal saline solution over 3 weeks. | Other | Intravenous saline infusions |
Primary outcome
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cristina S Albott, MD, MA principal investigator
Minneapolis Veterans Affairs Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ketamine and Normal Saline in people with Post-Traumatic Stress Disorders and Major Depressive Disorder, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2025.