Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04889664
Recruitment Status : Recruiting
First Posted : May 17, 2021
Last Update Posted : August 6, 2021
Sponsor:
Information provided by (Responsible Party):
Adriana Feder, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE May 12, 2021
First Posted Date  ICMJE May 17, 2021
Last Update Posted Date August 6, 2021
Actual Study Start Date  ICMJE June 4, 2021
Estimated Primary Completion Date May 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2021)
CAPS-5 [ Time Frame: up to 12 weeks ]
Clinician Administered PTSD Scale for DSM-5 (CAPS-5), assessed weekly between 3 weeks and up to 12 weeks following the start of WET, or until loss of response (whichever is shorter). 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD
Official Title  ICMJE Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD: A Pilot Study
Brief Summary The current project will evaluate the efficacy of adding Written Exposure Therapy (WET) to a course of repeated IV ketamine infusions in prolonging PTSD symptom improvement/time to loss of response 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 maintaining PTSD symptom improvement over time, in participants with chronic PTSD who respond to initial ketamine infusions. 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 time to loss of response in patients who show an initial response to ketamine, 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, regardless of initial response to ketamine. 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 longer maintenance of ketamine response. If demonstrated to prolong time to loss of response to ketamine, this novel combined treatment may represent a promising intervention for individuals with chronic PTSD, deserving further study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open label pilot study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE PTSD
Intervention  ICMJE
  • Drug: Ketamine
    Repeated intravenous Ketamine infusions.
  • Behavioral: Written Exposure Therapy
    WET is a brief, 5-session evidence-based written trauma-focused therapy
    Other Name: WET
Study Arms  ICMJE Experimental: Ketamine and Written Exposure Therapy
Intravenous Ketamine 0.5 mg/kg and Written Exposure Therapy
Interventions:
  • Drug: Ketamine
  • Behavioral: Written Exposure Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 12, 2021)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2025
Estimated Primary Completion Date May 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Men or women, 18-70 years of age;
  2. 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;
  3. 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 ≥ 25 at screening - this is done to ensure at least moderate severity and to safeguard against high placebo response rates;
  4. 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);
  5. Women of childbearing potential must have a negative pregnancy test at screening and prior to each intravenous infusion;
  6. 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;
  7. 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).

Exclusion Criteria:

  1. 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);
  2. 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;
  3. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
  4. Renal impairment, as reflected by a BUN >20 mg/dL, and/or creatinine clearance of >1.3 mg/dL;
  5. Clinically significant uncorrected hypothyroidism or hyperthyroidism, as indicated by a TSH value 25% above or below the normal range;
  6. A Body Mass Index (BMI) >40;
  7. Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first infusion day;
  8. History of a neurodevelopmental disorder (e.g., autism, pervasive developmental disorder) ;
  9. History of one or more seizures without a clear and resolved etiology;
  10. Lifetime history of bipolar I or II disorder;
  11. Presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder;
  12. Drug or alcohol use disorder within the preceding 3 months
  13. 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;
  14. Previous non-response to clinical or research ketamine or esketamine administration;
  15. Current diagnosis of bulimia nervosa or anorexia nervosa;
  16. Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
  17. SBP >165 and DBP >95 at infusion days - higher BP allowed to account for stress or anxiety;
  18. Concurrent treatment with opioid medication, or with long-acting or daytime short-acting benzodiazepines within two weeks of study start;
  19. Current cognitive impairment, as defined by a score <23 on the Montreal Cognitive Assessment (MoCA);
  20. Estimated IQ <80;
  21. 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Oneysha Brown, BA 212-585-4634 oneysha.brown@mssm.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04889664
Other Study ID Numbers  ICMJE IRB 21-00167
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: All of the individual participant data collected during the trial, after deidentification.
Supporting Materials: Informed Consent Form (ICF)
Time Frame: Immediately following publication. No end date.
Access Criteria: Researchers who provide a methodologically sound proposal. Any purpose. Upon receipt of request by PI, and after obtaining the necessary Data Transfer Agreement, PI will provide requested de-identified data via CSV file.
Current Responsible Party Adriana Feder, Icahn School of Medicine at Mount Sinai
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Icahn School of Medicine at Mount Sinai
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Adriana Feder, MD Depression and Anxiety Center, Icahn School of Medicine at Mount Sinai
Study Director: Oneysha Brown, BA Depression and Anxiety Center, Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP