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

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ClinicalTrials.gov Identifier: NCT02727998
Recruitment Status : Recruiting
First Posted : April 5, 2016
Last Update Posted : January 29, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

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.

Condition or disease Intervention/treatment Phase
Posttraumatic Stress Disorder Drug: Ketamine Drug: Midazolam Phase 2

Detailed Description:

Based on the current research findings on the therapeutic effectiveness of trauma focus psychotherapy and of ketamine, combining the two treatments may yield a promising new rapid 7-day treatment for PTSD. As PTSD symptoms' structure is comprised of several unique clusters which include re-experiencing, avoidance, numbing/depression and hypervigilance the investigators hypothesize that by combining Ketamine with prolonged exposure (PE) the investigators can address these symptoms clusters more effectively. This treatment has the potential to produce a significant therapeutic effect that otherwise would take months to occur by tapping on the enhanced neuroplasticity and the antidepressant effect of ketamine (which lasts between 24hrs to 7 days), to promote rapid changes in learning and memory using prolonged exposure therapy within this unique "window of opportunity".

During the first visit participants will undergo a clinical interview to establish a PTSD diagnosis and other eligibility criteria. If found eligible participants will be invited to take part in this 7-day rapid treatment trial for PTSD.

On the first therapy visits, participants will be educated about the psychological treatment that will be provided and the potential benefit of ketamine to enhance the psychotherapy outcomes.

On the second day of the study, participants will receive an infusion of ketamine and will undergo an magnetic resonance imaging (MRI) scan and will receive the second psychotherapy session.

On days 3-6 participants will attend a 60-90 minutes psychotherapy session to address their PTSD symptoms.

Day 7 will include another MRI scan and the last psychotherapy session.

Participants will be asked to come back for a follow up evaluation of their PTSD symptoms 30 and 90 days post discharge.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Combining Neurobiology and New Learning: Ketamine and Prolonged Exposure: A Potential Rapid Treatment for Post Traumatic Stress Disorder (PTSD)
Study Start Date : December 2015
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ketamine with prolonged exposure
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
Prolonged exposure therapy combined with a single infusion of 0.50 mg/kg/hour for 40 min on day 2.
Other Name: Ketalar

Active Comparator: Midazolam with prolonged exposure
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
Prolonged exposure therapy combined with a single infusion of 0.045 mg/kg/hour for 40 min on day 2.
Other Name: Versed




Primary Outcome Measures :
  1. Change from baseline to 90 days post treatment in Clinician-Administered PTSD Scale scores [ Time Frame: Baseline, 7 days, 30 days and 90 days ]
    Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). A higher score is associated with higher severity of PTSD. The score is interpreted as follows: 0-19=Asymptomatic/few symptoms 20-39=Sub-threshold/mild PTSD 40-59=Threshold PTSD/moderate 60-79=Severe PTSD >80=Extreme PTSD


Secondary Outcome Measures :
  1. Change from baseline to 90 days post treatment in Beck Depression Inventory (BDI-II) [ Time Frame: Baseline, 7 days, 30 days and 90 days ]
    The self-report BDI-II will be used to assess severity of depressive symptoms. A higher score is associated with higher severity of depression. The score is interpreted as follows: 0-13 indicates minimal depression, 14-19 indicates mild depression, 20-28 indicates moderate depression and 29-63 indicates severe depression



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female between the ages of 21-55 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.

Exclusion Criteria:

  • 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.
  • Body weight of 250 pounds or greater.
  • History of claustrophobia.
  • Presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening questionnaire.
  • Donation of blood in excess of 500 mL within 56 days prior to dosing.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02727998


Contacts
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Contact: Ilan Harps-Rotem, PhD 203-937-4760 ilan.harpaz-rotem@yale.edu
Contact: Charles Gordon, MA 203-932-5711 ext 4326 charles.gordon@yale.edu

Locations
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United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06510
Contact: Ilan Harpaz-Rotem, PhD    203-937-4760    ilan.harpaz-rotem@yale.edu   
Contact: Charles Gordon, MA    203-932-5711 ext 4326    charles.gordon@yale.edu   
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Ilan Harpaz-Rotem, PhD Yale University

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02727998     History of Changes
Other Study ID Numbers: 1509016530
23260 ( Other Grant/Funding Number: NARSAD )
First Posted: April 5, 2016    Key Record Dates
Last Update Posted: January 29, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Data from the initial stage of the investigation will be used to establish support for a Phase 3 RCT.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Yale University:
PTSD

Additional relevant MeSH terms:
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Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Ketamine
Midazolam
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents