Clinical trial NCT05849493: Effects and Mechanisms of Change of Internet Delivered Cognitive Behavior Therapy for Generalized Anxiety Disorder
Official title: Effects and Mechanisms of Change of Internet Delivered Cognitive Behavior Therapy for Generalized Anxiety Disorder Based on Intolerance of Uncertainty or Metacognitive Theory
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Generalized Anxiety Disorder
Keywords: internet delivered treatment
digital mental health services
psychiatry
cognitive behavior therapy
intolerance of uncertainty
metacognitive theory
mechanisms of change
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Region Stockholm
First posted: 2023-05-09
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare two psychological treatments for Generalized Anxiety Disorder. The main questions it aims to answer are:

How well do these treatments work compared to earlier studies? Is one of the treatments more effective than the other? Are the treatments working the way that we think they do? Specifically, do changes in the variables that these treatments aim to target predict changes in anxiety symptoms?

Participants will be randomized to two different internet-based cognitive behavioral therapy (ICBT) programs: Intolerance of uncertainty-based ICBT and metacognition-based ICBT. Both programs consist of 8 treatment modules and run for 10 weeks. A psychologist will respond to the participants assignments and exercises and will respond to messages.

Detailed description: A randomized trial will be conducted within the Internet Psychiatry Clinic in Stockholm. An option will be added to the online sign-up form giving potential patients the option to participate in a treatment for GAD as part of this study. Based on information provided in the sign-up-form and an assessment via video-call with a psychologist, patients will be included/excluded.

Included patients will be randomized (1:1) to two different ICBT treatment programs (IU-ICBT and Meta-ICBT). These programs will be implemented into regular care at the Internet Psychiatry Clinic in Stockholm, meaning that each patient will undergo the regular assessment process at the clinic. Both programs are ICBT programs of similar scope, consisting of 8 modules to be completed during 10 weeks. During this time patients read written material which instructs them to do specific exercises, answer specific questions and can message a psychologist at the clinic via the web-platform. Based on similar treatments on the Internet Psychiatry Clinic we expect around 10% drop-out.

The effectiveness of both forms of ICBT (meaning within-group change in symptoms during the ten-week treatment) will be compared to a meta-analysis of the effectiveness of traditional CBT for GAD (g = 0.80). When comparing the treatment programs to each other the threshold for a clinically relevant difference will be g = 0.24. A power analysis has shown that n=200 in each arm gives at least 80% power to detect an effect of that size.

Hypothesis 1: IU-ICBT and Meta-ICBT will be effective and equivalent in a benchmarking analysis.

Data-analysis: We plan to use multi-level modeling to utilize the increased power/precision we get from within-participant repeated measures.

Hypothesis 2: Changes in intolerance of uncertainty will statistically mediate the treatment effect in the IU-ICBT group. Changes in negative metacognitive beliefs about worry will statistically mediate the treatment effect in the Meta-ICBT group. The effect of both mediators will be moderated by level of intolerance uncertainty and negative metacognitive beliefs at baseline. We will also compare the putative mediators to each other with the hypothesis that the mediation-effect will be stronger for the specific mediator that a treatment protocol targets.

Data-analysis: Participants will fill out weekly questionnaires which will include our putative mediators (MCQ-30 and IU-12 questionnaires) and their current symptom level (GAD-7 questionnaire). The mediation-effect of both treatment protocols will be analyzed using latent growth curve modeling which is considered suitable for the study of moderation and mediation in clinical trials.

Additional hypotheses: In addition to the primary hypotheses, we may also investigate alternative moderators proposed by the literature. Worry behaviors is hypothesised to moderate treatment effect in the IU-ICBT group since that treatment partially has a behavioral treatment focus. Emotional contrast avoidance will also be investigated as a moderator.

Eligibility criteria: Inclusion criteria:

* 18 years or older.
* Meet diagnostic criteria for GAD according to DSM-5, as assessed by a psychologist on a video-call.
* Self-rated score \> 10 on GAD-7.
* Can read and speak Swedish fluently.
* Have access to a smartphone, tablet, or computer and a Swedish BankID which allows access to the video-calls and treatment platform.
* Have the time and possibility to participate in the 10 week treatment.
* Consents to participate.

Exclusion criteria:

* Patients that are judged to be in greater need of another psychiatric treatment for another psychiatric diagnosis (for example severe depression) and/or is judged to have a high risk of suicide.
* Current drug or alcohol abuse.
* Current severe somatic health concern or social vulnerability if this is judged to be too great an obstacle for the patient to carry out the treatment.

Primary outcomes:
measure: Change in Generalized Anxiety Disorder-7 score (GAD-7)
timeFrame: From treatment start to 10 weeks after treatment start
measure: Change in Meta-Cognitions Questionnaire-30 score (MCQ-30, negative meta-cognition sub-scale)
timeFrame: From treatment start to 10 weeks after treatment start
measure: Change in Intolerance of Uncertainty Scale-12 score (IUS-12)
timeFrame: From treatment start to 10 weeks after treatment start
Secondary outcomes:
measure: Penn-State Worry Questionnaire (PSWQ)
timeFrame: 10 weeks - pre- and post-treatment.
measure: Contrast Avoidance Questionnaire-Worry (CAQ-W)
timeFrame: 10 weeks - pre- and post-treatment.
measure: Montomery-Asberg Depression Rating Scale - Self-rated (MADRS-S)
timeFrame: 10 weeks - pre- and post-treatment.
measure: Meta-Cognitions Qquestionnaire-30 (MCQ-30 - full scale)
timeFrame: 10 weeks - pre- and post-treatment.
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: 10 weeks - pre- and post-treatment.
measure: World Health Organization Disability Assessment Schedule 2.0
timeFrame: 10 weeks - pre- and post-treatment.
measure: Client satisfaction questionnaire (adapted to the clinic)
timeFrame: 10 weeks after treatment start.
measure: Worry Behavior Inventory (WBI)
timeFrame: 10 weeks - pre- and post-treatment.
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Internet Psychiatry Clinic, Psychiatry Southwest, SLSO, Region Stockholm
state: Huddinge
Study officials:
affiliation: Karolinska Institutet
name: Erik Forsell, PhD
role: PRINCIPAL_INVESTIGATOR
References: