PTSDPhase 2NCT04560660

Ketamine-enhanced Prolonged Exposure Therapy in PTSD

A Phase 2 study testing Ketamine and Midazolam in people with PTSD, run by VA Office of Research and Development at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to test the safety and efficacy of repeated doses of ketamine as compared to placebo to reduce symptoms of Posttraumatic Stress Disorder (PTSD) among Veteran receiving Prolonged Exposure Therapy. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: PTSD
What is being tested?: Ketamine and Midazolam
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 73 participants
Where: 1 siteUnited States
Study dates: 9 Mar 2021to 7 Oct 2025
Phase: Phase 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

male or female Veterans between the ages of 18 and 75 years
diagnosis of PTSD
ability to provide written informed consent

Who cannot join

females who are currently pregnant or breastfeeding
current high risk for suicide
history of moderate/severe head injury
history of psychosis
current episode of mania/hypomania
severe substance and/or alcohol use disorder in the last 6 months

Trial locations and contacts

1 site in 1 country.

United States1 site

Minneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, 55417-2309

Other trials in United States

About this study

Official title: Repeated Ketamine Treatment to Accelerate Efficacy of Prolonged Exposure in PTSD

Read the detailed description

In this single site clinical trial, intended to evaluate the safety and efficacy of repeated doses of ketamine in conjunction with prolonged exposure (PE) therapy for PTSD. Veterans who meet criteria for PTSD and the additional inclusion and exclusion criteria will be randomized to one of two treatment arms (placebo plus PE vs ketamine plus PE). Participants receive the study drug via intravenous infusion once per week for 3-weeks.

Conditions: PTSD
Being tested: Ketamine, Midazolam
Keywords: Post-traumatic Stress Disorder
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.

KetamineDrug
FDA approved anesthetic medication with rapid acting antidepressant effects.
MidazolamDrug
FDA approved sedative medication with dissociative effects.

Study groups in NCT04560660
Study group	Role	What they receive
Ketamine and prolonged exposure (PE)	Experimental	Single IV ketamine 0.5 mg/kg 24-72 hrs prior to PE session at week 1,2, and 3 followed by 7 additional PE sessions. Receives: Drug: Ketamine
Midazolam and prolonged exposure (PE)	Placebo comparator	Single IV midazolam 0.045 mg/kg 24-72 hrs prior to PE session at week 1,2, and 3 followed by 7 additional PE sessions. Receives: Drug: Midazolam

What is being measured

The primary outcome is the main question the study is designed to answer.

Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.
Measured: Baseline
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.
Measured: Week 4
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.
Measured: Week 10
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.
Measured: Week 14
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.
Measured: Week 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Mar 20217 Oct 2025

First posted23 Sep 2020
Study start9 Mar 2021
Primary completion1 Jul 2025
Study completion7 Oct 2025

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.
Other trials for PTSDStudies of the same condition, open and under way.
More trials run by VA Office of Research and DevelopmentThe 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Subjects will be randomly assigned to one of two parallel treatment conditions: 1) adjunctive ketamine infusions to prolonged exposure therapy or 2) adjunctive midazolam (active placebo) infusions to prolonged exposure therapy.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 73 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04560660
Sponsor's protocol ID: MHBP-006-19F
Status last verified: Jul 2026
First submitted: 17 Sep 2020
Last updated: 11 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All PTSD trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Repeated Ketamine Treatment to Accelerate Efficacy of Prolonged Exposure in PTSD
ClinicalTrials.gov ID: NCT04560660
Acronym / sponsor ID: MHBP-006-19F
Conditions: PTSD
Keywords: Post-traumatic Stress Disorder
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 73 participants (actual)
Lead sponsor: VA Office of Research and DevelopmentUS federal agency
Study start: 9 Mar 2021 (actual)
Primary completion: 1 Jul 2025 (actual)
Study completion: 7 Oct 2025 (actual)
First posted: 23 Sep 2020 (actual)
Results: Posted 15 Jul 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Subjects will be randomly assigned to one of two parallel treatment conditions: 1) adjunctive ketamine infusions to prolonged exposure therapy or 2) adjunctive midazolam (active placebo) infusions to prolonged exposure therapy.

Arm	Type	Receives
Ketamine and prolonged exposure (PE)	Experimental	Drug: KetamineSingle IV ketamine 0.5 mg/kg 24-72 hrs prior to PE session at week 1,2, and 3 followed by 7 additional PE sessions.
Midazolam and prolonged exposure (PE)	Placebo comparator	Drug: MidazolamSingle IV midazolam 0.045 mg/kg 24-72 hrs prior to PE session at week 1,2, and 3 followed by 7 additional PE sessions.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

male or female Veterans between the ages of 18 and 75 years
diagnosis of PTSD
ability to provide written informed consent

Key exclusion criteria (6 listed)

females who are currently pregnant or breastfeeding
current high risk for suicide
history of moderate/severe head injury
history of psychosis
current episode of mania/hypomania

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
KetamineFDA approved anesthetic medication with rapid acting antidepressant effects.	Drug	Ketamine and prolonged exposure (PE)
MidazolamFDA approved sedative medication with dissociative effects.	Drug	Midazolam and prolonged exposure (PE)

Primary outcome

Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time frame: Baseline
The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time frame: Week 4
The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time frame: Week 10
The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time frame: Week 14
The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time frame: Week 22
The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.

Results and safety

Results posted to the registry on 15 Jul 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ketamine and Prolonged Exposure (PE)	37	20
Midazolam and Prolonged Exposure (PE)	36	19

Primary outcome: Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

Time frame: Baseline. Mean (Standard Deviation). Unit: units on a scale

Measure	Ketamine and Prolonged Exposure (PE) n = 37	Midazolam and Prolonged Exposure (PE) n = 36
Value	42.1 (9.3)	41.9 (11.0)

Population analysed: The variability in the number of participants for data points resulted from a variety of reasons for example participants not showing up for appointments, dropping out of the study and/or illness.

Primary outcome: Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

Time frame: Week 4. Mean (Standard Deviation). Unit: units on a scale

Measure	Ketamine and Prolonged Exposure (PE) n = 25	Midazolam and Prolonged Exposure (PE) n = 19
Value	34.0 (13.4)	36.7 (13.0)

Primary outcome: Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

Time frame: Week 10. Mean (Standard Deviation). Unit: units on a scale

Measure	Ketamine and Prolonged Exposure (PE) n = 13	Midazolam and Prolonged Exposure (PE) n = 10
Value	25.3 (17.0)	26.8 (16.8)

Primary outcome: Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

Time frame: Week 14. Mean (Standard Deviation). Unit: units on a scale

Measure	Ketamine and Prolonged Exposure (PE) n = 16	Midazolam and Prolonged Exposure (PE) n = 14
Value	19.3 (16.4)	21.6 (13.6)

Adverse events

Time frame: from enrollment until end of follow-up (~22 weeks). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ketamine and Prolonged Exposure (PE)	1 of 37 (2.7%)	33 of 37 (89.2%)	0 of 37
Midazolam and Prolonged Exposure (PE)	1 of 36 (2.8%)	34 of 36 (94.4%)	0 of 36

Limitations and caveats (from the sponsor): The study did not achieve its planned sample size due to delays in hiring research therapists, which reduced our dedicated research capacity. To maintain study operations, the investigators relied on clinical therapists; however, their availability was constrained by ongoing clinical responsibilities. This competition with clinical demands further limited the number of participants who could be enrolled during the recruitment period.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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 VA Health Care System, Minneapolis, MN

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ketamine and Midazolam in people with PTSD, run by VA Office of Research and Development 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 3 inclusion and 6 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 11 Aug 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. 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 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 15 Jul 2026). 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?

Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) (time frame: Baseline). The study lists 5 primary outcomes in all. 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 NCT04560660.

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 11 Aug 2026.