Clinical TrialPTSDKetamineKetaminePlaceboRecruiting

Enhancing Week-long Psychological Treatment for PTSD With Ketamine

Randomised, parallel Phase II trial (n=162) comparing two ketamine IV doses (0.2 mg/kg and 0.5 mg/kg; two infusions) vs midazolam (active comparator) combined with week-long trauma-focused psychotherapy for chronic PTSD.

Target Enrollment
162 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

This parallel-group, randomised Phase II trial evaluates whether combining two IV ketamine infusions with intensive trauma-focused psychotherapy over one week produces greater PTSD symptom reduction than midazolam plus the same psychotherapy.

Participants receive psychotherapy education at the first visit, an infusion and MRI on day 2, psychotherapy sessions on days 3–6 (60–90 minutes each), a second infusion on day 4, and a post-treatment MRI on day 7; follow-up clinical assessments and one MRI at 30 days and clinical evaluation at 90 days assess durability.

Outcomes include PTSD symptom measures (CAPS-5), safety/tolerability, and neurophysiological changes on MRI to explore mechanistic effects of drug-augmented psychotherapy.

Study Protocol

Preparation

1 sessions

Dosing

2 sessions
40 min each

Integration

4 sessions

Therapeutic Protocol

cbt

Study Arms & Interventions

Ketamine 0.2 mg/kg

experimental

Two IV ketamine infusions (0.2 mg/kg) on days 2 and 4 combined with trauma-focused psychotherapy (week-long).

Interventions

  • Ketamine0.2 mg/kg
    via IV• two infusions• 2 doses total

    40-minute infusion on day 2 and day 4; clinical monitoring throughout.

Ketamine 0.5 mg/kg

experimental

Two IV ketamine infusions (0.5 mg/kg) on days 2 and 4 combined with trauma-focused psychotherapy (week-long).

Interventions

  • Ketamine0.5 mg/kg
    via IV• two infusions• 2 doses total

    40-minute infusion on day 2 and day 4; clinical monitoring throughout.

Midazolam

active comparator

Two IV midazolam infusions (active comparator) on days 2 and 4 combined with trauma-focused psychotherapy (week-long).

Interventions

  • Placebo0.045 mg/kg
    via IV• two infusions• 2 doses total

    Midazolam 0.045 mg/kg IV infusion over 40 minutes on days 2 and 4; encoded as active comparator (compound placeholder).

Participants

Ages
21 – 70
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Male or female between the ages of 21-70 years.
  • Must not have a medical/neurological problem or use medication that would render ketamine unsafe by history or medical evaluation.
  • Diagnosis of chronic PTSD with a score of 25 or higher on the Clinician-Administered PTSD Scale (CAPS-5) at screening; symptoms persisting >1 year.
  • Subjects on certain stable psychotropic treatments may enter if stable for at least 4 weeks prior to randomization.
  • Able to provide written informed consent and read/write English.

Exclusion Criteria

  • Exclusion Criteria:
  • Diagnostic history of borderline personality disorder, obsessive compulsive disorder, schizophrenia or schizoaffective disorder or current psychotic features; dementia or suspicion thereof.
  • History of bipolar disorder with a manic/hypomanic episode in the 30 days prior to enrollment (such patients excluded); other DSM Axis I disorders permitted if not primary.
  • History of antidepressant-induced hypomania or mania.
  • Current, ongoing serious suicidal risk as assessed by investigator using the Columbia-Suicide Severity Rating Scale (C-SSRS).
  • Moderate or greater Substance Use Disorder (excepting Alcohol and Marijuana) during the 3 months prior; alcohol or marijuana disorder may be allowed per clinician judgment.
  • Use of prohibited medications (see protocol Table 1) or recent use within specified washout periods.
  • History of TBI with prolonged LOC or PTA unless >1 year and minimal symptoms.
  • Positive pregnancy test or breastfeeding; positive pre-study urine drug screen (or per investigator discretion).
  • Resting BP <90/60 or >150/90 or HR <45 or >100 bpm.
  • Significant medical/neurological illness, ECG or lab abnormalities, claustrophobia, implanted electronic/ferromagnetic devices incompatible with MRI.
  • Recent blood donation >500 mL within 56 days; sensitivity to ketamine; body circumference ≥52 inches or weight ≥350 pounds.
  • Active engagement in trauma-focused CBT or evidence-based PTSD psychotherapy initiated within past 3 months; enrollment in another interventional research study affecting symptoms within last 2 months or planned within next 3 months.

Study Details

  • Status
    Recruiting
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Randomizedquadruple Blind
  • Target Enrollment162 participants
  • Timeline
    Start: 2023-08-21
    End: 2031-08-01
  • Compounds
    KetamineKetaminePlacebo
  • Topic
    PTSD

Locations

Yale University School of Medicine — New Haven, Connecticut, United States
Tel Aviv University — Tel Aviv, Israel

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