Intensive 7-day Treatment for PTSD Combining Ketamine With Exposure Therapy

NCT02727998 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 150901653023260
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to combine a single infusion of Ketamine with 7-days of trauma focus psychotherapy to relieve post traumatic stress disorder (PTSD) symptoms more effectively. This treatment has the potential to produce a significant therapeutic effect that otherwise would take months to occur.

Conditions

Posttraumatic Stress Disorder

Keywords

PTSD

Outcome Measures

Primary Outcomes (1)

• Change in PTSD Symptoms

  PTSD symptoms severity will be evaluated overtime using the PTSD Checklist for DSM-5 (PCL-5), a 20 items self-report measure. Items are scored 0-4 (0=not at all to 4=Extremely), thus total PCL-5 score ranges from 0 to 80. Higher scores reflect greater severity of PTSD. Total PCL-5 scores are reported. PCL score\>33 indicates probable PTSD diagnosis. Evidence for the PCL suggested 5 points reduction as a minimum threshold for determining whether an individual has responded to treatment and 10 points reduction in the PCL-5 as a minimum threshold for determining whether the improvement is clinically meaningful.

  Baseline, 7 days, 30 days and 90 days

Secondary Outcomes (1)

• Change in Beck Depression Inventory (BDI-II)

  Baseline, 7 days, 30 days and 90 days

Study Arms (2)

Single infusion of Ketamine with prolonged exposure

EXPERIMENTAL

After the reactivation of the scripted memories during PE on day 2, the ketamine infusion procedure will begin inside the MRI. A physician will oversee and administer the ketamine infusions. A nurse will accompany the subject throughout the study sessions, from the insertion of bilateral cannula for drug infusion and blood sampling, to the recovery following ketamine infusion. Whilst subjects undergo the infusion, their heart rate and blood pressure will be constantly monitored. The participant will receive a steady state ketamine infusion of 0.50 mg/kg/hour. The infusion will continue for 40 minutes.

Drug: Ketamine

Midazolam with prolonged exposure

ACTIVE COMPARATOR

After the reactivation of the scripted memories during PE on day 2, the midazolam infusion procedure will begin inside the MRI. A physician will oversee and administer the Midazolam infusions. A nurse will accompany the subject throughout the study sessions, from the insertion of bilateral cannula for drug infusion and blood sampling, to the recovery following midazolam infusion. Whilst subjects undergo the infusion, their heart rate and blood pressure will be constantly monitored. The participant will receive a steady midazolam infusions at a rate 0.045 mg/kg for 40 minutes.

Drug: Midazolam

Interventions

Ketamine DRUG

Prolonged exposure therapy combined with a single infusion of 0.50 mg/kg/hour for 40 min on day 2.

Also known as: Ketalar

Single infusion of Ketamine with prolonged exposure

Midazolam DRUG

Prolonged exposure therapy combined with a single infusion of 0.045 mg/kg/hour for 40 min on day 2.

Also known as: Versed

Midazolam with prolonged exposure

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between the ages of 21-75 years. This age range was chosen to fit with prior samples in which no adverse effects of ketamine have been observed. Adults in the 18-20 ranges have been eliminated because previous experience indicates that they often lack the maturity to participate effectively in similar protocols. Females will be included if they are not pregnant and agreed to utilize a medically accepted birth control method (to include oral, injectable, or implant birth control, condom, diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner with vasectomy) or if post-menopausal for at least 1 year, or surgically sterile.
• Able to provide written informed consent according to Yale HIC guidelines.
• Able to read and write English as a primary language.
• Diagnosis of PTSD, as determined by the Clinician Administered PTSD Scale (CAPS-5) (Weathers et al., 2013).
• Must have a score of 50 or higher on the Clinician-Administered PTSD Scale (CAPS-5) at screening.
• No more than mild Traumatic Brain Injury (TBI) according to a modified version of the Brief TBI Screen (Schwab, et al., 2006).
• Must not have a medical/neurological problem or use medication that would render ketamine unsafe by history or medical evaluation.

You may not qualify if:

• Patients with a diagnostic history of bipolar disorder, schizophrenia or schizoaffective disorder or currently exhibiting psychotic features as determined by the Structured Clinical Interview for DSM (SCID) (First, et al. 2010); dementia or suspicion thereof, are excluded. Other DSM Axis I disorders are permitted as long as they are not considered primary disorders.
• Patients with a history of antidepressant-induced hypomania or mania as determined by open-ended psychiatric interview.
• Serious suicide or homicide risk, as assessed by evaluating clinician; A serious suicide risk will be considered an inability to control suicide attempts, imminent risk of suicide in the investigator's judgment, or a history of serious suicidal behavior, which is defined using the Columbia-Suicide Severity Rating Scale (C-SSRS) (Posner et al., 2011) as either (1) one or more actual suicide attempts in the 3 years before study entry with the lethality rated at 3 or higher, or (2) one or more interrupted suicide attempts with a potential lethality judged to result in serious injury or death.
• Substance abuse or dependence during the 6 months prior to screening as determined by the Structured Clinical Interview for DSM (SCID).
• Any significant history of serious medical or neurological illness.
• Any signs of major medical or neurological illness on examination or as a result of electrocardiogram (ECG) screening or laboratory studies.
• Lifetime history of psychoactive substance or alcohol dependence or substance or alcohol abuse (other than nicotine or caffeine abuse), or drinking more than 5 drinks/week during the last year.
• Abnormality on physical examination. A subject with a clinical abnormality may be included only if the study physician considers the abnormality will not introduce additional risk factors and will not interfere with the study procedure.
• A positive pre-study (screening) urine drug screen or, at the study physician's discretion on any drug screens given before the scans.
• Pregnant or lactating women or a positive urine pregnancy test for women of child-bearing potential at screening or prior to any imaging day.
• Positive HIV or Hepatitis B tests. This test will take place at the screening visit. Subjects will be invited back to the Yale Depression Research Program either for their next study visit or for a HIV/Hep debriefing session. A study physician will inform them in person of the results. They will be given access to counselling and advised of the appropriate next steps.
• Has received either prescribed or over-the-counter (OTC) centrally active medicine or herbal supplements within 60 days of enrollment into the study. Subjects who have taken OTC medication or herbal supplements may still be entered into the study, if, in the opinion of the principal/co-investigator, the medication received will not interfere with the study procedures or compromise safety.
• Any history indicating learning disability, mental retardation, or attention deficit disorder.
• Known sensitivity to ketamine.
• Body circumference of 52 inches or greater.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Due to study termination, full enrollment was not achieved and therefore the intended regression modeling was not performed.

Results Point of Contact

• Title: Dr. Ilan Harpaz-Rotem
• Organization: Yale School of Medicine

ilan.harpaz-rotem@yale.edu

(203) 937-4760

Study Officials

• Ilan Harpaz-Rotem, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2016
• First Posted: April 5, 2016
• Study Start: December 1, 2015
• Primary Completion: November 28, 2021
• Study Completion: November 28, 2021
• Last Updated: October 17, 2022
• Results First Posted: October 17, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)