PTSDPhase 2NCT04889664
Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD
A Phase 2 study testing Ketamine and Written Exposure Therapy in people with PTSD, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
The current pilot project will evaluate the efficacy of adding Written Exposure Therapy (WET) to a course of repeated IV ketamine infusions in improving PTSD symptoms and maintaining symptom improvement in patients with chronic PTSD. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- PTSD
- What is being tested?
- Ketamine and Written Exposure Therapy
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jun 2021to 14 Oct 2023
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women, 18-70 years of age;
- Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document;
- Participants must fulfill DSM-5 criteria for current civilian or combat-related PTSD, based on clinical assessment by a study psychiatrist and on the CAPS-5, and a past-month total CAPS5 score ≥ 30 at screening - this is done to ensure at least moderate severity and to safeguard against high placebo response rates;
- Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year);
- Women of childbearing potential must have a negative pregnancy test at screening and prior to each intravenous infusion;
- Men who are sexually active with women of childbearing potential must use a medically accepted reliable means of contraception and must agree not to donate sperm for a period of 90 days after receiving the last dose of ketamine;
- Participants must be able to identify a family member, physician, or friend (i.e. someone who knows them well) who will participate in a Treatment Contract (and e.g. contact the study physician on their behalf in case manic symptoms or suicidal thoughts develop).
Who cannot join
- Women who plan to become pregnant, are pregnant or are breast-feeding (because the medical risk of using ketamine during pregnancy and breast-feeding is unknown);
- Serious, unstable medical illnesses such as hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, including gastro-esophageal reflux disease, obstructive sleep apnea, history of difficulty with airway management during previous anesthetics, ischemic heart disease and uncontrolled hypertension, and history of severe head injury;
- Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
- Renal impairment, as reflected by a BUN >20 mg/dL, and/or creatinine clearance of >1.3 mg/dL;
- Clinically significant uncorrected hypothyroidism or hyperthyroidism, as indicated by a TSH value 25% above or below the normal range;
- A Body Mass Index (BMI) >40;
Show all 22Show fewer
- Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first infusion day;
- History of a neurodevelopmental disorder (e.g., autism, pervasive developmental disorder) ;
- History of one or more seizures without a clear and resolved etiology;
- Lifetime history of bipolar I or II disorder;
- Presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder;
- Drug or alcohol use disorder within the preceding 3 months
- Previous recreational use of ketamine or PCP on more than one occasion, or any recreational use of ketamine or PCP within the last two years;
- Previous non-response to clinical or research ketamine or esketamine administration;
- Current diagnosis of bulimia nervosa or anorexia nervosa;
- Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
- SBP >165 and DBP >95 at infusion days - higher BP allowed to account for stress or anxiety;
- Concurrent treatment with opioid medication, or with long-acting or daytime short-acting benzodiazepines within two weeks of study start;
- Current cognitive impairment, as defined by a score <23 on the Montreal Cognitive Assessment (MoCA);
- Estimated IQ <80;
- Currently receiving evidence-based psychotherapy for PTSD (e.g., prolonged exposure, cognitive processing therapy);
- Note: Concurrent treatment with other psychotropic medications (including a short-acting benzodiazepine at bedtime only) will be permitted, but dose must be stabilized for at least three months before study start.
Trial locations and contacts
1 site in 1 country.
United States1 site
Depression and Anxiety Center, Icahn School of Medicine at Mount Sinai
Manhattan, New York, 10029
About this study
Official title: Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD: A Pilot Study
The current pilot project will evaluate the efficacy of adding Written Exposure Therapy (WET) to a course of repeated IV ketamine infusions in improving PTSD symptoms and maintaining symptom improvement in patients with chronic PTSD. WET is a brief, 5-session evidence-based written trauma-focused therapy without in between-session assignments, with demonstrated efficacy and low dropout rates in patients with PTSD. WET will be administered to all eligible participants; the first WET sessions will be interleaved with the last two ketamine infusions to take advantage of a window of increased neuroplasticity potentially induced by repeated ketamine infusions. WET will be administered on different days as the ketamine infusions.
Read the detailed description
Current treatments for PTSD do not work for a significant proportion of individuals with PTSD, or work only partially, leaving persistent and disabling residual symptoms. The research team has led the development of ketamine for the treatment of chronic PTSD. After the initial, proof-of-concept randomized controlled trial (RCT) of a single ketamine infusion in individuals with chronic PTSD showed promising results, the study team recently completed the first RCT of repeated intravenous ketamine infusions where individuals with chronic PTSD received a course of six ketamine infusions (vs. active placebo midazolam infusions) and demonstrated a rapid and robust improvement in PTSD symptoms. Median time to loss of response, however, occurred a few weeks following the course of infusions, making it imperative to investigate novel approaches aimed at preventing symptom relapse following ketamine treatment. The study team proposes a proof-of-concept, open-label pilot study to evaluate the efficacy of adding an evidence-based, brief and scalable trauma-focused psychotherapy, Written Exposure Therapy (WET), to a course of ketamine infusions in improving PTSD symptoms and maintaining symptom improvement, in participants with chronic PTSD. To accomplish this aim, the study team will enroll individuals who meet DSM-5 criteria for chronic PTSD. Eligible patients will receive a total of six ketamine infusions and will participate in WET (a total of five sessions). The primary outcome will be change in PTSD symptom severity from baseline to 12 weeks from the start of WET, assessed with the Clinician-Administered PTSD Scale for DSM-5. Additionally, all participants will be assessed weekly until 12 weeks following the start of WET. Thereafter, participants who remain improved will be assessed monthly for up to 24 weeks. The study team will also evaluate whether extinction learning ability -assessed with a computerized extinction learning task- predicts maintenance of ketamine response over time, and will explore potential sociodemographic and clinical predictors of treatment response. If demonstrated to have preliminary efficacy, this novel combined treatment may represent a promising intervention for individuals with chronic PTSD, deserving further study.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Repeated intravenous Ketamine infusions.
Written Exposure TherapyBehavioural
Also called WET
WET is a brief, 5-session evidence-based written trauma-focused therapy
| Study group | Role | What they receive |
|---|---|---|
| Ketamine and Written Exposure Therapy | Experimental | Intravenous Ketamine 0.5 mg/kg and Written Exposure Therapy Receives: Drug: Ketamine; Behavioral: Written Exposure Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
CAPS-5
Clinician Administered PTSD Scale for DSM-5 (CAPS-5), assessed at baseline (before the first infusion) and 12 weeks following the start of WET. The Clinician-Administered PTSD Scale (CAPS) is a 30-item structured diagnostic interview designed to measure frequency and intensity of PTSD symptoms. The symptoms are scored in a 0-4 Likert-type scale, total score ranging from 0 to 80, higher score indicates more symptoms
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2021
- Study start4 Jun 2021
- Primary completion14 Oct 2023
- Study completion14 Oct 2023
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 PTSDStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- Open label pilot study
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adriana Feder, Icahn School of Medicine at Mount Sinai
- Investigators
- Adriana Feder, MD, Principal investigator, Depression and Anxiety Center, Icahn School of Medicine at Mount SinaiOneysha Brown, BA, Study director, Depression and Anxiety Center, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04889664
- Sponsor's protocol ID
- STUDY-21-00167
- Status last verified
- Sep 2024
- First submitted
- 12 May 2021
- Last updated
- 8 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after deidentification.
Publications
Feder A, Brown O, Rutter SB, Cahn L, Overbey JR, Seeley SH, Yu A, Bonanno PA, Fremont RA, Delgado AA, Jha MK, Costi S, Yehuda R, Schiller D, Pietrzak RH, Charney DS, Sloan DM, Murrough JW. Combining Ketamine Infusions and Written Exposure Therapy for Chronic PTSD: An Open-Label Trial. J Clin Psychiatry. 2025 Apr 2;86(2):24m15622. doi: 10.4088/JCP.24m15622.
PubMed 40215385
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD: A Pilot Study
- ClinicalTrials.gov ID
- NCT04889664
- Acronym / sponsor ID
- STUDY-21-00167
- Conditions
- PTSD
- Keywords
- ketamine, Written Exposure Therapy, PTSD, intervention, treatment, posttraumatic stress disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- 4 Jun 2021 (actual)
- Primary completion
- 14 Oct 2023 (actual)
- Study completion
- 14 Oct 2023 (actual)
- First posted
- 17 May 2021 (actual)
- Results
- Posted 8 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current pilot project will evaluate the efficacy of adding Written Exposure Therapy (WET) to a course of repeated IV ketamine infusions in improving PTSD symptoms and maintaining symptom improvement in patients with chronic PTSD. WET is a brief, 5-session evidence-based written trauma-focused therapy without in between-session assignments, with demonstrated efficacy and low dropout rates in patients with PTSD. WET will be administered to all eligible participants; the first WET sessions will be interleaved with the last two ketamine infusions to take advantage of a window of increased neuroplasticity potentially induced by repeated ketamine infusions. WET will be administered on different days as the ketamine infusions.
Detailed description
Current treatments for PTSD do not work for a significant proportion of individuals with PTSD, or work only partially, leaving persistent and disabling residual symptoms. The research team has led the development of ketamine for the treatment of chronic PTSD. After the initial, proof-of-concept randomized controlled trial (RCT) of a single ketamine infusion in individuals with chronic PTSD showed promising results, the study team recently completed the first RCT of repeated intravenous ketamine infusions where individuals with chronic PTSD received a course of six ketamine infusions (vs. active placebo midazolam infusions) and demonstrated a rapid and robust improvement in PTSD symptoms. Median time to loss of response, however, occurred a few weeks following the course of infusions, making it imperative to investigate novel approaches aimed at preventing symptom relapse following ketamine treatment. The study team proposes a proof-of-concept, open-label pilot study to evaluate the efficacy of adding an evidence-based, brief and scalable trauma-focused psychotherapy, Written Exposure Therapy (WET), to a course of ketamine infusions in improving PTSD symptoms and maintaining symptom improvement, in participants with chronic PTSD. To accomplish this aim, the study team will enroll individuals who meet DSM-5 criteria for chronic PTSD. Eligible patients will receive a total of six ketamine infusions and will participate in WET (a total of five sessions). The primary outcome will be change in PTSD symptom severity from baseline to 12 weeks from the start of WET, assessed with the Clinician-Administered PTSD Scale for DSM-5. Additionally, all participants will be assessed weekly until 12 weeks following the start of WET. Thereafter, participants who remain improved will be assessed monthly for up to 24 weeks. The study team will also evaluate whether extinction learning ability -assessed with a computerized extinction learning task- predicts maintenance of ketamine response over time, and will explore potential sociodemographic and clinical predictors of treatment response. If demonstrated to have preliminary efficacy, this novel combined treatment may represent a promising intervention for individuals with chronic PTSD, deserving further study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label pilot study
| Arm | Type | Receives |
|---|---|---|
| Ketamine and Written Exposure Therapy | Experimental | Drug: Ketamine, Behavioral: Written Exposure TherapyIntravenous Ketamine 0.5 mg/kg and Written Exposure Therapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Men or women, 18-70 years of age;
- Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document;
- Participants must fulfill DSM-5 criteria for current civilian or combat-related PTSD, based on clinical assessment by a study psychiatrist and on the CAPS-5, and a past-month total CAPS5 score ≥ 30 at screening - this is done to ensure at least moderate severity and to safeguard against high placebo response rates;
- Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year);
- Women of childbearing potential must have a negative pregnancy test at screening and prior to each intravenous infusion;
Key exclusion criteria (22 listed)
- Women who plan to become pregnant, are pregnant or are breast-feeding (because the medical risk of using ketamine during pregnancy and breast-feeding is unknown);
- Serious, unstable medical illnesses such as hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, including gastro-esophageal reflux disease, obstructive sleep apnea, history of difficulty with airway management during previous anesthetics, ischemic heart disease and uncontrolled hypertension, and history of severe head injury;
- Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
- Renal impairment, as reflected by a BUN >20 mg/dL, and/or creatinine clearance of >1.3 mg/dL;
- Clinically significant uncorrected hypothyroidism or hyperthyroidism, as indicated by a TSH value 25% above or below the normal range;
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 |
|---|---|---|
| KetamineRepeated intravenous Ketamine infusions. | Drug | Ketamine and Written Exposure Therapy |
| Written Exposure TherapyAlso: WETWET is a brief, 5-session evidence-based written trauma-focused therapy | Behavioural | Ketamine and Written Exposure Therapy |
Primary outcome
CAPS-5
Time frame: Baseline and Week 12
Clinician Administered PTSD Scale for DSM-5 (CAPS-5), assessed at baseline (before the first infusion) and 12 weeks following the start of WET. The Clinician-Administered PTSD Scale (CAPS) is a 30-item structured diagnostic interview designed to measure frequency and intensity of PTSD symptoms. The symptoms are scored in a 0-4 Likert-type scale, total score ranging from 0 to 80, higher score indicates more symptoms
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40215385Feder A, Brown O, Rutter SB, Cahn L, Overbey JR, Seeley SH, Yu A, Bonanno PA, Fremont RA, Delgado AA, Jha MK, Costi S, Yehuda R, Schiller D, Pietrzak RH, Charney DS, Sloan DM, Murrough JW. Combining Ketamine Infusions and Written Exposure Therapy for Chronic PTSD: An Open-Label Trial. J Clin Psychiatry. 2025 Apr 2;86(2):24m15622. doi: 10.4088/JCP.24m15622.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after deidentification.
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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.
Adriana Feder, MD principal investigator
Depression and Anxiety Center, Icahn School of Medicine at Mount Sinai
Oneysha Brown, BA study director
Depression and Anxiety Center, Icahn School of Medicine at Mount Sinai
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 Written Exposure Therapy in people with PTSD, run by Icahn School of Medicine at Mount Sinai 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 7 inclusion and 22 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 8 Oct 2024. 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 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 8 Oct 2024). 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?
CAPS-5 (time frame: Baseline and Week 12). 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 NCT04889664, 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 8 Oct 2024.