Effects and Mechanisms of Change of Internet Delivered Cognitive Behavior Therapy for Generalized Anxiety Disorder (ORIGAMI)

Effects and Mechanisms of Change of Internet Delivered Cognitive Behavior Therapy for Generalized Anxiety Disorder Based on Intolerance of Uncertainty or Metacognitive Theory

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.

Study Overview

• Status: Recruiting
• Conditions: Generalized Anxiety Disorder
• Intervention / Treatment: Behavioral: Intolerance of uncertainty based Internet delivered Cognitive Behavior Therapy; Behavioral: Metacognitive Internet delivered Cognitive Behavior Therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vilgot Huhn, MSc; Phone Number: +46768482613; Email: vilgot.huhn@ki.se
• Study Contact Backup: Name: Erik Forsell, PhD; Phone Number: +46704903681; Email: erik.forsell@ki.se

Study Locations

• Sweden
  • Huddinge
    • Stockholm, Huddinge, Sweden, 14135
      • Recruiting
      • Internet Psychiatry Clinic, Psychiatry Southwest, SLSO, Region Stockholm
      • Contact: Erik Forsell; Phone Number: 0704903681; Email: erik.forsell@ki.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IU-ICBT; 10 week program of internet delivered cognitive behavior therapy with written support by licensed clinical psychologist. Based on the Intolerance of uncertainty model of worry.	Behavioral: Intolerance of uncertainty based Internet delivered Cognitive Behavior Therapy; Specialist Guided Internet delivered Cognitive Behavior Therapy based on the Intolerance of uncertainty model of excessive worry
Experimental: Meta-ICBT; 10 week program of internet delivered cognitive behavior therapy with written support by licensed clinical psychologist. Based on the Metacognitive model of worry.	Behavioral: Metacognitive Internet delivered Cognitive Behavior Therapy; Specialist Guided Internet delivered Cognitive Behavior Therapy based on the metacognitive model of excessive worry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Generalized Anxiety Disorder-7 score (GAD-7)	Measures Generalized Anxiety Symptoms. 7 items. Scores range from 0-21 with higher scores indicating more generalized anxiety	From treatment start to 10 weeks after treatment start
Change in Meta-Cognitions Questionnaire-30 score (MCQ-30, negative meta-cognition sub-scale)	Putative mediator. The MCQ-30 negative subscale measures negative meta-cognitive beliefs about the danger and uncontrollability of worry. 6 items. Scores range from 6-36 with higher scores indicating more negative beliefs about worry.	From treatment start to 10 weeks after treatment start
Change in Intolerance of Uncertainty Scale-12 score (IUS-12)	Putative mediator, measures intolerance of uncertainty. 12 items. Scores range from 12-60 with higher scores indicating more intolerance of uncertainty.	From treatment start to 10 weeks after treatment start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Penn-State Worry Questionnaire (PSWQ)	Measures trait worry. 16 items. Scores range from 16-80 with higher scores indicating more worry.	10 weeks - pre- and post-treatment.
Contrast Avoidance Questionnaire-Worry (CAQ-W)	measures Contrast Avoidance related to worry. 25 items. Scores range from 30 to 150 with higher scores indicating a higher degree of using worry to avoid emotional contrasts.	10 weeks - pre- and post-treatment.
Montomery-Asberg Depression Rating Scale - Self-rated (MADRS-S)	Measures depression symptoms. 9 items. Scores range from 0 to 54 with higher scores indicating more depressive symptoms.	10 weeks - pre- and post-treatment.
Meta-Cognitions Qquestionnaire-30 (MCQ-30 - full scale)	Measures metacognition. 30 items. Scores range from 30-120 with higher scores indicating more potentially dysfunctional metacognitive beliefs about thoughts and worry.	10 weeks - pre- and post-treatment.
Patient Health Questionnaire-9 (PHQ-9)	Measures depression symptoms. 9 items. Scores range from 0-27 with higher scores indicating more depressive symptoms.	10 weeks - pre- and post-treatment.
World Health Organization Disability Assessment Schedule 2.0	Measures disability/functional impairment. 12 items. Scores range from 0-48 with higher scores indicating a higher degree of impairment.	10 weeks - pre- and post-treatment.
Client satisfaction questionnaire (adapted to the clinic)	Measures satisfaction with treatment. 8 items. Scores range from 8-32 with higher scores indicating more satisfaction with the treatment.	10 weeks after treatment start.
Worry Behavior Inventory (WBI)	Inventory of worry behaviors - 10 items. Scores range from 0-40 with higher scores indicating more frequent worry behaviours.	10 weeks - pre- and post-treatment.

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Region Stockholm
• Investigators: Principal Investigator: Erik Forsell, PhD, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 4, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: cognitive behavior therapy; psychiatry; intolerance of uncertainty; internet delivered treatment; digital mental health services; metacognitive theory; mechanisms of change
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: 2022-02380-01-RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Patient records not available to share.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No