Combined Ketamine and eCBT Intervention for PTSD

Study Overview
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Brief Summary
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An open label RCT assessing the efficacy of a combined treatment approach for PTSD, using Ketamine infusions and online Cognitive Behavioural Therapy.

Detailed Description
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OBJECTIVES (i) To introduce a previously untreated patient population with PTSD to new therapeutic options. (ii) To provide new insights into the functional role of Glutamate in affective disorders as well as in learning and memory. (iii) To explore the utility of pharmacologically-enhanced psychotherapy. OUTLINE The present study is an open label randomized control trial assessing the efficacy of a combined treatment of sub-anaesthetic IV Ketamine in conjunction with online CBT (eCBT). In the study, 16 participants with refractory PTSD will be assigned either to an experimental group receiving a combination of Ketamine and eCBT over 12 weeks, or they will be assigned to a 12-week control group. Both groups will be assessed for symptoms of PTSD and comorbid disorders before treatment, at 2 midway points (4 and 8 weeks), and at the end of the 12 week experimental period. Symptoms of PTSD and comorbid disorders for participants in the experimental group are expected to improve significantly more than participants in the control.

Official Title
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Assessing a Combined Ketamine and Online Cognitive Behavioural Therapy Intervention for Treatment Resistant Post-Traumatic Stress Disorder

Conditions
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Post-Traumatic Stress Disorder

Intervention / Treatment
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* Drug: Ketamine
* Behavioral: Online Trauma-Focused Cognitive Behavioural Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PTSD by a psychiatrist on the team using the Clinician Administered PTSD Scale (CAPS-5) with a score of at least 50 and a medium presentation. Patients will have received at least 2 different types of prior treatment, both of which produced less than a 50% reduction in the participant's symptoms. Participants with hypertension or cardiovascular disease must be receiving stable treatment to participate. Participants must speak and read English, and will have consistent and reliable access to the internet. Patients with suicidal ideation will be included. Patients with a history of substance abuse will be included (except for opioid use disorder). Exclusion Criteria: Hypomanic/manic episodes, bipolar disorder, acute psychosis, opioid use disorder, treatment with Naltrexone, pregnancy, postpartum, breastfeeding, untreated hypertension, cardiovascular disease, ASPD, active homicidal ideation, and general noncompliance with the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants diagnosed with PTSD will be assigned either to the experimental treatment or a control. Data will be collected from participants in both groups at the same 4 time-points.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine + eCBT<br>Over 12 weeks, participants receive weekly sessions of asynchronous online cognitive-behavioural therapy as well as 6 sub-anesthetic infusions of Ketamine | Drug: Ketamine<br>* Patients will receive 6 sub-anesthetic IV ketamine infusions over 8 weeks, each one lasting 40 minutes.<br>* Other names: Ketalar;Behavioral: Online Trauma-Focused Cognitive Behavioural Therapy<br>* Participants will enrol in a 12-week online CBT program mirroring in-person trauma-focused CBT.<br>* Other names: TF-CBT;|
| No Intervention: Control<br>Participants are in a control condition receiving treatment as usual, during which time they will not receive the experimental treatment and will have no change in their treatment regimen. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Scores on the Clinician Administered PTSD Scale for DSM-5 | Assessment of PTSD symptoms for diagnosis and severity; score representing the mildest/lack of symptoms: 0; score representing the most severe symptoms: 120. | 0 weeks from start, 4 weeks from start, 8 weeks from start, and 12 weeks from start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Scores on the Montgomery Asberg Depression Rating Scale | Measure of depression; score representing the mildest/lack of symptoms: 0; score representing the most severe symptoms: 60. | 0 weeks from start, 4 weeks from start, 8 weeks from start, and 12 weeks from start | 
| Change in Scores on the Columbia Suicide Severity Rating Scale | Measuring thoughts, feelings, and behaviours associated with suicide; score representing the mildest/lack of symptoms: 0; score representing the most severe symptoms: 6. | 0 weeks from start, 4 weeks from start, 8 weeks from start, and 12 weeks from start | 
| Change in Scores on the Sheehan Disabilities Scale | A brief, patient rated measure of disability and impairment; score representing the mildest/lack of symptoms: 0; score representing the most severe symptoms: 44. | 0 weeks from start, 4 weeks from start, 8 weeks from start, and 12 weeks from start | 
| Change in Scores on the Global Assessment of Functioning | Assessing the patient's overall capacity to handle life's challenges; score representing the mildest/lack of symptoms: 100; score representing the most severe symptoms: 1. | 0 weeks from start, 4 weeks from start, 8 weeks from start, and 12 weeks from start | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine, Cognitive Behavioral Therapy, Online Cognitive Behavioral Therapy, Pharmacologically enhanced psychotherapy