Efficacy of Internet-delivered Cognitive-behavior Therapy for PTSD

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare therapist-guided internet delivered prolonged exposure to an active control condition( therapist-guided internet delivered cognitive behavioral therapy containing relaxation techniques) for post-traumatic stress disorder. The objective with this study is to investigate efficacy, mechanisms of change and cost effectiveness of therapist-guided internet delivered prolonged exposure. Adult patients with post-traumatic stress disorder will be randomly assigned to receive either 10 weeks of therapist-guided internet delivered prolonged exposure or therapist-guided internet delivered cognitive-behavioral therapy containing relaxation.

Detailed Description
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PTSD is a debilitating psychiatric disorder strongly linked to subsequent psychiatric and medical problems. Trauma-focused cognitive behavioral therapy (CBT-T) such as prolonged exposure is an effective treatment for PTSD and is recommended in most clinical guidelines as first-line treatment but is seldom available in regular care. A possible solution to significantly improve access to evidence-based treatment would be the use of remotely delivered digital intervention. Preliminary research shows that therapist-guided internet delivered to be effective and safe, but studies have typically excluded patients with severe PTSD. Before this type of treatment can be offered in regular care in Sweden, it needs to be further evaluated also with psychiatric patients suffering from severe PTSD. If therapist-guided internet delivered prolonged exposure would be found to effective, this project has the potential to be the first step towards implementation of a novel, superior and more cost-effective mode of treatment delivery for adults with PTSD in regular Swedish health care. The study is a single-blind, parallel-group superiority randomized controlled trial with 284 patients (142 per arm) that will compare therapist-guided internet delivered prolonged exposure with therapist-guided internet delivered cognitive-behavioral therapy The primary outcome is the blind-rater administered Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes are cost effectiveness, mediators of change, dropout rate, and negative effects. The trial will also be preregistered at the Open Science Framework. Research questions to be answered are: Is guided i-CBT with exposure more efficacious than an active control condition (therapist-supported internet-delivered psychoeducation, relaxation and support) in regard to reduction of blinded assessor rated PTSD symptom severity 1-month post-treatment? Is guided i-CBT with exposure more cost-effective than an active control condition (therapist-supported internet-delivered psychoeducation, relaxation and support) in regard to reduction of blinded assessor rated PTSD symptom severity 1-month post-treatment? Are the therapeutic gains of i-CBT maintained at long term follow up (6 and 12 months after treatment)? Is guided i-CBT with exposure more efficacious than an active control condition (therapist-supported internet-delivered psychoeducation, relaxation and support) in regard to reduction in depressive symptoms and increase in quality of life up to 12 months after treatment completion? What are the mediators of change in guided i-CBT for PTSD?

Official Title
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Efficacy and Mediators of Change of Cognitive-behavior Therapy for PTSD: a Randomized Controlled Trial

Conditions
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Post Traumatic Stress Disorder

Intervention / Treatment
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* Behavioral: Therapist-supported internet-delivered prolonged exposure
* Behavioral: Therapist-supported internet-delivered CBT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: current primary diagnosis PTSD according to DSM-5 diagnostic criteria be 18 years of age or older be able to read and communicate fluently in Swedish have had a stable dose of any psychotropic medication for at least 4 weeks prior to study entry Daily access to a computer or device with internet connection Exclusion Criteria: PTSD is not the primary concern Initiation or adjustment of any psychotropic medication within the last 4 weeks prior to commencement of treatment Serious mental health symptoms, such as mania, psychosis, alcohol, or substance use disorders or current suicide risk warranting immediate clinical attention. Ongoing trauma-focused CBT or Eye movement desensitization and reprocessing therapy Ongoing trauma-related threat (e.g. living with a violent spouse)

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapist-supported internet delivered prolonged exposure<br>Therapist-supported internet delivered prolonged exposure comprising psychoeducation about PTSD, controlled breathing, imaginal exposure including processing, in vivo exposure and relapse prevention. The treatment will be delivered in a digital platform for ten weeks. Participants will have access to a therapist that will guide them through treatment in a text based format. | Behavioral: Therapist-supported internet-delivered prolonged exposure<br>* 10 weeks of therapist-supported internet-delivered prolonged exposure<br>|
| Active Comparator: Therapist-supported CBT<br>Therapist-supported CBT internet-delivered treatment comprising psychoeducation about PTSD, relaxation techniques and relapse prevention. . The treatment will be delivered in a digital platform for ten weeks. Participants will have access to a therapist that will guide them through treatment in a text based format. | Behavioral: Therapist-supported internet-delivered CBT<br>* 10 weeks of therapist-supported internet-delivered CBT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PTSD symptoms as assessed by the Clinician Administered PTSD Scale (CAPS-5) | The CAPS-5 is structured interview that assesses the Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-5) criteria for PTSD (Weathers et al., 2013). Each item is rated on a severity scale ranging from 0 (Absent) to 4 (Extreme/incapacitating) and combines information about frequency and intensity for each of the 20 symptoms. Total Score (Range 0-80 with higher scores representing more PTSD symptoms. | Baseline, 1-month (primary endpoint), 6-month and 12-month post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PTSD symptoms as assessed by the PTSD Check List - DSM-5 (PCL-5) | The PCL-5 is a 20-item self-report measure based upon the Diagnostic and Statistical Manual (DSM-5) criteria for PTSD. Total Score (Range 0-80 with higher scores representing more PTSD symptoms. | Baseline, through the treatment period up to 10 weeks and 1-month, 6-month and 12-month post-treatment] | 
| Change in ICD-11 PTSD and complex PTSD symptoms as assessed by the International Trauma Questionnaire (ITQ). | The ITQ includes six items measuring each PTSD symptom cluster and these items measure how bothersome each symptom has been in the past month. The ITQ also includes six items measuring each 'Disturbance in Self-Organization' (DSO) symptom in complex PTSD. These items measure how a respondent typically feels, thinks about oneself, and relates to others. The PTSD and DSO symptoms are accompanied by three items measuring associated functional impairments in the domains of social, occupation, and other important areas of life. All items are answered on a 5-point Likert scale ranging from 0 (Not at all) to 4 (Extremely). Thus, PTSD and DSO symptom scores range from 0 to 24 and CPTSD symptom scores range from 0 to 48. Higher scores represents more PTSD and complex PTSD symptoms. | Baseline, immediately after treatment completion, 1-month, 6-month and 12-month post-treatment | 
| Change in depressive symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9) | The PHQ-9 is a widely used and well-validated instrument for measuring the severity of depressive symptoms. Scores are calculated based on how frequently a person experiences 9 symptoms of depression ranging from not at all response is scored as 0; several days response is 1; more than half the days response is 2; and nearly every day response is 3. Higher scores represents more depressive symptoms. | Baseline, immediately after treatment completion, 1-month, 6-month and 12-month post-treatment | 
| Change in quality of life measured by Euroqol, EQ-5D | Change in overall health from baseline to post treatment and follow up . EQ-5D is a standardized self-report measure of overall health status measured in terms of five dimensions; mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension measures performance in work, study, housework, family or leisure activities. In pain/discomfort dimension, it asks how much pain or discomfort they have, and in anxiety/depression dimension, it asks how anxious or depressed they are. The respondents self-rate their level of severity for each dimension using a three-level scale: 1 having no problems, 2 having some problems and 3 having extreme problems. A higher score indicate worse severity. | Baseline, immediately after treatment completion, 1-month, 6-month and 12-month post-treatment | 
| Change in Assessing Quality of Life 6 Dimensions (AQoL-6D) | Used to assess cost-effectiveness. 20 questions that assess different aspects of quality of life. The AQoL provides a utility score that ranges from 1.00 (full health) to 0.00 (death-equivalent health states) to -0.04 (health states worse than death. | Baseline, immediately after treatment completion, 1-month, 6-month and 12-month post-treatment | 
| Change in Treatment Inventory of Costs in Psychiatric Patients (TIC-P) | Self-rated questionnaire on healthcare utilization and productivity losses in patients with a psychiatric disorder. The TIC-P questionnaire measures costs in two dimensions: use of health resources and loss of productivity. Lower cost is better. | Baseline, immediately after treatment completion, 1-month, 6-month and 12-month post-treatment | 
| Adverse events related to treatment measured by the Negative effects questionnaire | Self-rated questionnaire on negative effects. It contains 32 items that are scored on a five point Likert-scale (0-4) and differentiates between negative effects that are attributed to treatment and those possibly caused by other circumstances. The total score of the NEQ ranges from 0 to 80 points, a higher score reflects more negative effects. | Immediately after treatment completion, 1-month, 6-month and 12-month post-treatment | 
| Participants satisfaction with treatment, assessed by The Client Satisfaction Questionnaire (CSQ-8). | The CSQ-8 yields a single score measuring a single dimension of overall satisfaction. An overall score is calculated by summing the score on each of the eight scale item. Scores range from 8 to 32, with higher values indicating higher satisfaction. | Immediately after treatment completion | 
| Number of completed treatment modules | Data will be gathered on total number of completed modules during the 10 week treatment. | Baseline up to treatment completion at 10 weeks | 
| Number of messages sent and received in the digital platform | Data will be gathered on total number of messages sent and received back and forth between the participant and the therapist during the 10 week treatment. | Baseline up to treatment completion at 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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therapist-assisted treatment, prolonged exposure, trauma focused CBT, PTSD, therapist-guided treatment, internet delivered treatment, digital treatment