Post-traumatic Stress DisorderPhase 1/2NCT03960658
Ketamine and Prolonged Exposure in PTSD
A Phase 1/2 study testing ketamine-enhanced prolonged exposure in people with Post-traumatic Stress Disorder, run by Minneapolis Veterans Affairs Medical Center at 1 site in United States.
Trial summary
This study aims at investigating the effectiveness of the drug, Ketamine, in combination with Prolonged Exposure (PE) therapy for people suffering from PTSD. Participation in the study includes Ketamine infusions, which occur once a week for three weeks. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Post-traumatic Stress Disorder
- What is being tested?
- ketamine-enhanced prolonged exposure
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Apr 2019to 4 Dec 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of chronic (minimum of three months) PTSD (Clinician-Administered PTSD Scale for DSM-5 -CAPS-5 score>33).
- Voluntarily eligible to participate in PE.
- Severity of PTSD symptoms defined by PCL-5>33.
- Psychotropic medications on stable doses (no dosing adjustments/changes for ≥4 weeks; ≥6 weeks for fluoxetine) prior to prior to beginning of the study.
Who cannot join
- Unwillingness/unable to sign informed consent.
- Previous or current participation in trauma-exposed therapy and/or ketamine treatment.
- Evidence of mental retardation, pervasive developmental disorder and/or moderate/severe cognitive impairment (MMSE scores ≤27).
- Any unstable medical or non-psychiatric CNS condition.
- Lifetime history of psychosis-related disorder, bipolar disorder I or II disorder, or any condition other than PTSD judged to be the primary presenting psychiatric diagnosis.
- Moderate to severe traumatic brain injury (mental status change or loss of consciousness>30 min; Glasgow Coma Scale <13; post-traumatic amnesia>24hours; visible lesion on CT/MRI brain scan).
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- Active alcohol/illicit substance use disorder within 6 months of initial assessment; presence of illicit drugs by positive urine toxicology.
- For women: pregnancy (confirmed by lab test), initiation of female hormonal treatments within 3 months of screening, or inability/ unwillingness to use a medically accepted contraceptive method during the study.
- Imminent risk of suicidal/homicidal ideation and/or behavior with intent and/or plan
Trial locations and contacts
1 site in 1 country.
United States1 site
Minneapolis VA Medical Center
Minneapolis, Minnesota, 55417
About this study
Official title: Repeated Sub-anesthetic Ketamine to Enhance Prolonged Exposure Therapy in Post-traumatic Stress Disorder: A Proof-of-concept Study
This study aims at investigating the effectiveness of the drug, Ketamine, in combination with Prolonged Exposure (PE) therapy for people suffering from PTSD. Participation in the study includes Ketamine infusions, which occur once a week for three weeks. PE therapy sessions will be scheduled one day after each infusion, and may continue up to 12 weeks. After completely therapy, there will be two monthly follow-up assessment visits.
Read the detailed description
Study location: Minneapolis VA Medical Center
The study is an open-label interventional study designed to inform and strengthen the feasibility of protocol implementation on sub-anesthetic doses of intravenous Ketamine as augmenting strategy of standardized, manually-driven Prolonged Exposure therapy in PTSD.
Timeline: Eligible individuals can expect their participation to last up to 5 months. Compensation will be given for participation per session that is attended. Potential participants will be provided with information about the study and asked a series of questions to determine if they meet basic inclusion/exclusion criteria (e.g., indicators of current PTSD). They will be informed that the treatment involves multiple infusions of sedatives at subanesthetic doses followed by PE therapy. Those interested will be scheduled for an in-person, baseline session.
Voluntary informed consent will be obtained in accordance with local IRB approvals. During the baseline, all assessments, computer tasks, and information on treatment will be explained. Participants will also undergo a urine toxicology analysis during this session. Ketamine infusions and PE therapy appointments will be scheduled within two weeks of the baseline.
The day of the infusion, patients will arrive in the morning after an overnight fast of at least 8 hours. An IV will be placed in the non-dominant arm for medication administration. Vitals will be recorded throughout the entire medication treatment. Subjects will then receive IV infusion of 0.5mg/Kg of ketamine hydrochloride solution over 40 minutes. The dose of ketamine will be calculated by ideal body weight. Any altered sensory or dissociative effects will be measured before and after each infusion. Vitals will be monitored for another hour, until all side-effects have subsided. Participants are required not to drive or use heavy machinery until the following morning.
One day after the infusion, patients will come back for study assessments and Prolonged Exposure therapy with a VA psychologist. PE is an evidence-based psychotherapy for PTSD that is based on the Emotional Processing Theory of PTSD; the four components of PE are: 1) exposure to safe situations, objects, or people that cause distress and are avoided because they are trauma reminders (in vivo exposure), 2) revisiting and processing of the trauma memory (imaginal exposure), 3) psycho-education about trauma-related symptoms, and 4) breathing retraining. Session 1 includes the presentation of treatment rationale and program overview, information gathering, and breathing retraining. Session 2 includes education about common reactions to trauma, rationale for in vivo exposure, and construction of an in vivo exposure hierarchy. The hierarchy includes safe or low-risk activities and situations that were avoided because of their association with the trauma. Throughout the treatment, participants will be assigned homework to confront items on the hierarchy in a gradual fashion, working up to the most anxiety-arousing situations. During Session 3, the rationale for confronting the trauma memory in imagination is presented and initiation of imaginal exposure and processing is conducted. In this procedure, participants will be asked to close their eyes, visualize the trauma, and recount it aloud in the present tense for 45-60 min. The memory recounting will be repeated if necessary to allow total reliving of 45-60 min. The exposure will be audiotaped; participants will be instructed to listen daily to the tape. Sessions 4-10 will be conducted in a similar fashion: therapists review homework, conduct imaginal exposure to trauma memory for 30-45 min, discuss the imaginal exposure, and assigned in vivo and imaginal exposure homework. In the final session, participants summarize learning in treatment, discuss their progress, plans, and relapse prevention.
Upon PE completion, participants are asked to come back for 2 follow-up sessions over two months. Familiar study and PTSD assessments will be administered during this time.
- Conditions
- Post-traumatic Stress Disorder
- Being tested
- ketamine-enhanced prolonged exposure
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ketamine-enhanced prolonged exposureDrug
Subjects will receive a single infusion of racemic ketamine at 0.5mg/kg (ideal body weight) for 40 minutes. The next day, patients will have a standardized prolonged exposure session which lasts approximately 90 minutes. This co-jointed intervention will be repeated for 3 weeks. Then, patients will continue with therapy sessions to complete a total of 10-12 sessions.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine and PE | Experimental | ketamine treatment followed by a standardized prolonged exposure session for the first 3 weeks; then, weekly prolonged exposure as usual. Receives: Drug: ketamine-enhanced prolonged exposure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Severity of Post-traumatic Stress Disorder (PTSD) Symptoms
The overall severity of PTSD symptoms would be measured by the mean change in the Past Month (current) total scores on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (CAPS-5) from baseline to post-treatment (10 weeks). The CAPS-5 is a structured interview with higher values representing worse outcomes. The CAPS-5 total symptom severity score ranges from 0 to 80 and it is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms.
Measured: 10 weeks
Secondary outcomes (2)
Change in Severity of Depressive Symptoms
Total score on the Montgomery- Åsberg Depression Rating Scale , a semi- structured 10-item scale. Range 0-60. Higher values represent worse outcomes. The total score is obtained by summing the severity score of each item.
Measured: 10 weeks
Change in PTSD Symptoms for DSM-5
The PTSD Checklist for DSM-5 (PCL5) is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Range from 0-80. Higher values represent worse outcomes.
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2019
- Study start3 Apr 2019
- Primary completion18 Nov 2019
- Study completion4 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-traumatic Stress DisorderStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label study
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Minneapolis Veterans Affairs Medical Center
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Paulo Shiroma, Minneapolis Veterans Affairs Medical Center
- Investigators
- Paulo R Shiroma, MD, Principal investigator, Minneapolis Veterans Affairs Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03960658
- Sponsor's protocol ID
- VAM-18-00333
- Status last verified
- Oct 2026
- First submitted
- 20 May 2019
- Last updated
- 14 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shiroma PR, Thuras P, Wels J, Erbes C, Kehle-Forbes S, Polusny M. A Proof-of-Concept Study of Subanesthetic Intravenous Ketamine Combined With Prolonged Exposure Therapy Among Veterans With Posttraumatic Stress Disorder. J Clin Psychiatry. 2020 Nov 10;81(6):20l13406. doi: 10.4088/JCP.20l13406. No abstract available.
PubMed 33176074
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repeated Sub-anesthetic Ketamine to Enhance Prolonged Exposure Therapy in Post-traumatic Stress Disorder: A Proof-of-concept Study
- ClinicalTrials.gov ID
- NCT03960658
- Acronym / sponsor ID
- VAM-18-00333
- Conditions
- Post-traumatic Stress Disorder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Minneapolis Veterans Affairs Medical CenterUS federal agency
- Study start
- 3 Apr 2019 (actual)
- Primary completion
- 18 Nov 2019 (actual)
- Study completion
- 4 Dec 2019 (actual)
- First posted
- 23 May 2019 (actual)
- Results
- Posted 22 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims at investigating the effectiveness of the drug, Ketamine, in combination with Prolonged Exposure (PE) therapy for people suffering from PTSD. Participation in the study includes Ketamine infusions, which occur once a week for three weeks. PE therapy sessions will be scheduled one day after each infusion, and may continue up to 12 weeks. After completely therapy, there will be two monthly follow-up assessment visits.
Detailed description
Study location: Minneapolis VA Medical Center
The study is an open-label interventional study designed to inform and strengthen the feasibility of protocol implementation on sub-anesthetic doses of intravenous Ketamine as augmenting strategy of standardized, manually-driven Prolonged Exposure therapy in PTSD.
Timeline: Eligible individuals can expect their participation to last up to 5 months. Compensation will be given for participation per session that is attended. Potential participants will be provided with information about the study and asked a series of questions to determine if they meet basic inclusion/exclusion criteria (e.g., indicators of current PTSD). They will be informed that the treatment involves multiple infusions of sedatives at subanesthetic doses followed by PE therapy. Those interested will be scheduled for an in-person, baseline session.
Voluntary informed consent will be obtained in accordance with local IRB approvals. During the baseline, all assessments, computer tasks, and information on treatment will be explained. Participants will also undergo a urine toxicology analysis during this session. Ketamine infusions and PE therapy appointments will be scheduled within two weeks of the baseline.
The day of the infusion, patients will arrive in the morning after an overnight fast of at least 8 hours. An IV will be placed in the non-dominant arm for medication administration. Vitals will be recorded throughout the entire medication treatment. Subjects will then receive IV infusion of 0.5mg/Kg of ketamine hydrochloride solution over 40 minutes. The dose of ketamine will be calculated by ideal body weight. Any altered sensory or dissociative effects will be measured before and after each infusion. Vitals will be monitored for another hour, until all side-effects have subsided. Participants are required not to drive or use heavy machinery until the following morning.
One day after the infusion, patients will come back for study assessments and Prolonged Exposure therapy with a VA psychologist. PE is an evidence-based psychotherapy for PTSD that is based on the Emotional Processing Theory of PTSD; the four components of PE are: 1) exposure to safe situations, objects, or people that cause distress and are avoided because they are trauma reminders (in vivo exposure), 2) revisiting and processing of the trauma memory (imaginal exposure), 3) psycho-education about trauma-related symptoms, and 4) breathing retraining. Session 1 includes the presentation of treatment rationale and program overview, information gathering, and breathing retraining. Session 2 includes education about common reactions to trauma, rationale for in vivo exposure, and construction of an in vivo exposure hierarchy. The hierarchy includes safe or low-risk activities and situations that were avoided because of their association with the trauma. Throughout the treatment, participants will be assigned homework to confront items on the hierarchy in a gradual fashion, working up to the most anxiety-arousing situations. During Session 3, the rationale for confronting the trauma memory in imagination is presented and initiation of imaginal exposure and processing is conducted. In this procedure, participants will be asked to close their eyes, visualize the trauma, and recount it aloud in the present tense for 45-60 min. The memory recounting will be repeated if necessary to allow total reliving of 45-60 min. The exposure will be audiotaped; participants will be instructed to listen daily to the tape. Sessions 4-10 will be conducted in a similar fashion: therapists review homework, conduct imaginal exposure to trauma memory for 30-45 min, discuss the imaginal exposure, and assigned in vivo and imaginal exposure homework. In the final session, participants summarize learning in treatment, discuss their progress, plans, and relapse prevention.
Upon PE completion, participants are asked to come back for 2 follow-up sessions over two months. Familiar study and PTSD assessments will be administered during this time.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label study
| Arm | Type | Receives |
|---|---|---|
| Ketamine and PE | Experimental | Drug: ketamine-enhanced prolonged exposureketamine treatment followed by a standardized prolonged exposure session for the first 3 weeks; then, weekly prolonged exposure as usual. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of chronic (minimum of three months) PTSD (Clinician-Administered PTSD Scale for DSM-5 -CAPS-5 score>33).
- Voluntarily eligible to participate in PE.
- Severity of PTSD symptoms defined by PCL-5>33.
- Psychotropic medications on stable doses (no dosing adjustments/changes for ≥4 weeks; ≥6 weeks for fluoxetine) prior to prior to beginning of the study.
Key exclusion criteria (9 listed)
- Unwillingness/unable to sign informed consent.
- Previous or current participation in trauma-exposed therapy and/or ketamine treatment.
- Evidence of mental retardation, pervasive developmental disorder and/or moderate/severe cognitive impairment (MMSE scores ≤27).
- Any unstable medical or non-psychiatric CNS condition.
- Lifetime history of psychosis-related disorder, bipolar disorder I or II disorder, or any condition other than PTSD judged to be the primary presenting psychiatric diagnosis.
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 |
|---|---|---|
| ketamine-enhanced prolonged exposureSubjects will receive a single infusion of racemic ketamine at 0.5mg/kg (ideal body weight) for 40 minutes. The next day, patients will have a standardized prolonged exposure session which lasts approximately 90 minutes. This co-jointed intervention will be repeated for 3 weeks. Then, patients will continue with therapy sessions to complete a total of 10-12 sessions. | Drug | Ketamine and PE |
Primary outcome
Change in Severity of Post-traumatic Stress Disorder (PTSD) Symptoms
Time frame: 10 weeks
The overall severity of PTSD symptoms would be measured by the mean change in the Past Month (current) total scores on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (CAPS-5) from baseline to post-treatment (10 weeks). The CAPS-5 is a structured interview with higher values representing worse outcomes. The CAPS-5 total symptom severity score ranges from 0 to 80 and it is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms.
2 secondary outcomes
Change in Severity of Depressive Symptoms
Time frame: 10 weeks
Change in PTSD Symptoms for DSM-5
Time frame: 10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33176074Shiroma PR, Thuras P, Wels J, Erbes C, Kehle-Forbes S, Polusny M. A Proof-of-Concept Study of Subanesthetic Intravenous Ketamine Combined With Prolonged Exposure Therapy Among Veterans With Posttraumatic Stress Disorder. J Clin Psychiatry. 2020 Nov 10;81(6):20l13406. doi: 10.4088/JCP.20l13406. No abstract available.
- Individual participant dataSharing planned: No
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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.
Paulo R Shiroma, MD 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 1/2 study testing ketamine-enhanced prolonged exposure in people with Post-traumatic Stress Disorder, run by Minneapolis Veterans Affairs Medical Center 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 4 inclusion and 9 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 14 Oct 2026. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Severity of Post-traumatic Stress Disorder (PTSD) Symptoms (time frame: 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03960658, which also lists 1 linked publication.
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 14 Oct 2026.