Improving anxiety treatment by modifying emotional memories before real-life exposure
| ISRCTN | ISRCTN29668369 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN29668369 |
| Secondary identifying numbers | MREC Utrecht: Source ID: NL73918.041 |
- Submission date
- 24/05/2022
- Registration date
- 27/06/2022
- Last edited
- 28/08/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Mental and Behavioural Disorders
Plain English Summary
Background and study aims
Many people suffer from an anxiety-related disorder. They typically suffer from excessive fear in anticipation or the presence of feared (innocuous) stimuli and avoidance of disorder-related situations. For instance, patients with panic disorder suffer from an intense fear of certain bodily sensations (e.g., heart palpitations) and situations that provoke them (e.g., drinking coffee, exercise). During exposure therapy, patients are systematically confronted with feared disorder-related stimuli and situations. This way, they can learn that the anticipated feared outcome does not occur (e.g., having a heart attack), which reduces their anxiety. Exposure-based therapy is one of the most effective treatments for anxiety disorders, but many patients do not benefit sufficiently from it. Distressing images of threat, related to the content of the anxiety disorder (e.g. having a heart attack), may maintain anxiety symptoms or reduce exposure therapy effectiveness. A treatment that targets these distressing images is eye movement desensitization and reprocessing (EMDR) therapy. The main goal of this study is to examine whether EMDR therapy with exposure therapy (ET), compared to supportive counseling with exposure therapy, improves treatment efficacy, tolerability, and adherence in patients with panic disorder.
Who can participate?
Patients aged 18 years and over with panic disorder
What does the study involve?
Participants are allocated (at random) to one of two groups. Those in the first group receive four 90-minute sessions of EMDR followed by eight 90-minute sessions of ET. Those in the second group receive four 90-minute sessions of SC and eight 90-minute sessions of ET. Both groups will receive manualized treatment by trained and supervised staff. Researcher assistants or graduate students blind to group allocation will conduct assessments before treatment (T1), between treatments (T2) and after treatments (T3). Panic-related symptoms are measured to assess how well EMDR works. The researchers further assess whether EMDR also works to improve the tolerability of exposure therapy (less initial avoidance, more willingness to start exposure therapy, less considered drop-out; less no-show and drop-out) and reduce functional impairment as well as related psychiatric symptoms (e.g. generalized anxiety, depression).
What are the possible benefits and risks of participating?
The benefit of participating is that people will receive a well-controlled treatment for panic disorder and possibly gain more benefits from our new treatment approach. To the researchers' knowledge, there are no additional risks or negative effects compared to treatment as usual. Due to assessments, study participation will take more time compared to treatment as usual.
Where is the study run from?
The study is run from two mental healthcare institutions in the Netherlands: Altrecht (i.e., Altrecht Academic Anxiety Center) and Mondriaan/PsyQ (i.e., Academic Anxiety Center).
When is the study starting and how long is it expected to run for?
January 2020 to December 2024
Who is funding the study?
Netherlands Organization of Scientific Research (NWO) (Netherlands)
Who is the main contact?
Prof. Iris M. Engelhard
i.m.engelhard@uu.nl
Contact information
Principal Investigator
Heidelberglaan 1
Utrecht
3584 CS
Netherlands
| Phone | +31 (0)634103344 |
|---|---|
| i.m.engelhard@uu.nl |
Scientific
Heidelberglaan 1
Utrecht
3584 CS
Netherlands
 ORCID ID |
0000-0002-4425-514X |
|---|---|
| Phone | +31 (0)613257610 |
| b.endhoven@uu.nl |
Public
Heidelberglaan 1
Utrecht
3584 CS
Netherlands
| Phone | +31 (0)613257610 |
|---|---|
| b.endhoven@uu.nl |
Study information
| Study design | Multicenter interventional single-blind randomized controlled trial with a two-arm mixed factorial design |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format |
| Scientific title | Reducing panic-related symptoms through eye movement desensitization and reprocessing therapy or supportive counseling before exposure therapy in patients with panic disorder: a randomized controlled trial |
| Study acronym | IMPROVE |
| Study hypothesis | The first goal of this research is to investigate whether eye movement desensitization and reprocessing (EMDR) therapy, compared to supportive counseling (SC), prior to exposure therapy (ET) improves treatment efficacy, tolerability, and adherence in patients with panic disorder. It is hypothesized that: 1. EMDR therapy is more effective in reducing panic-related symptoms, compared to SC from baseline (T1) to between-treatment (T2) 2. EMDR + ET is more effective in reducing panic-related symptoms, compared to SC+ET at post-treatment (T3) 3. EMDR therapy results in higher tolerability of exposure therapy (less initial avoidance, more willingness to start exposure therapy, less considered drop-out; less no-show and actual drop-out) compared to SC It is further hypothesized that: 4. EMDR therapy is more effective in reducing related symptomatology (generalized anxiety, depression) and functional impairment, compared to SC from baseline (T1) to between-treatments (T2) 5. EMDR + ET is more effective in reducing related symptomatology (generalized anxiety, depression) and functional impairment, compared to SC+ET at post-treatment (T3) Hypotheses concerning the following goals will be preregistered at the Open Science Framework (OSF; osf.ip). The second goal is to unravel predictors of optimal treatment allocation (EMDR+ET > SC+ET). These include theory-driven variables (reduced extinction learning, less experienced life events, low intolerance of uncertainty, anxiety sensitivity, low worrying, enhanced imagery ability), patient variables (e.g. greater treatment credibility, better working alliance) and therapist factors (e.g. enhanced trait anxiety, better working alliance, greater treatment expectancy). The third goal is to elucidate mechanisms of change (most notably mental threat imagery, encapsulated threat beliefs) of this novel approach (EMDR+ET). Finally, the researchers will assess the cost-effectiveness of the new approach (EMDR+ET). |
| Ethics approval(s) | Approved 26/08/2020, amendment approved 08/02/2023, Medical Research Ethics Committee UMC Utrecht (MREC NedMec, PO Box 85500, 3508 GA Utrecht, Netherlands; +31 (0)88 7556376; info@metcutrecht.nl), ref: NL73918.041 |
| Condition | Panic disorder |
| Intervention | Patients will be randomized (by computer) to one of two conditions: (1) four EMDR sessions followed by eight ET sessions or (2) four SC sessions followed by eight ET sessions. Sessions will take 90 min (once weekly) and will be provided face to face or online by videoconferencing. The total treatment duration is 16 weeks (week 1: baseline measurement T1, week 2: case conceptualization, week 3-6: treatment phase 1; EMDR or SC, week 7: between-treatments measurement T2, week 8-15: treatment phase 2; ET, week 16: post-treatment T3). Follow up 1 (FU1) and follow up 2 (FU2) will be conducted 1 month and 6 months post-treatment (T3). |
| Intervention type | Behavioural |
| Primary outcome measure | Panic-related symptoms: 1. Panic disorder severity (self-report) is measured with a questionnaire: Panic Disorder Severity Scale (PDSS-SR), total severity score at T1, T2, T3, FU1, FU2 and once weekly during the intervention phase 2. Panic disorder severity is measured using an interview: Panic Agoraphobia Scale (PAS), total severity score and panic attack frequency at T1, T2, T3 and FU1 |
| Secondary outcome measures | Other anxiety symptomatology (avoidance, safety behavior, panic disorder cognitions, diagnosis): 1. Avoidance is measured with the Fear Questionnaire-Agoraphobia (FQ-A), total severity score at T1, T2, T3, FU1, FU2 2. Safety behavior is measured with the Subtle Avoidance Frequency Examination-Agoraphobia (SAFE-A) questionnaire, total severity score at T1, T2, T3, FU1, FU2 3. Panic disorder cognitions are measured with the Bodily Sensation Questionnaire (BSQ), total severity score at T1, T2, T3, FU1, FU2 4. Panic disorder diagnosis is measured with an interview: Mini-International Neuropsychiatric Interview Simplified (MINI-S-DSM-V), diagnosis yes/no at T1 and FU1 Treatment tolerability: 1. Behavioral avoidance is measured with a standardized interoceptive exposure task: total avoidance score at ET session 1 and ET session 8 2. Exposure willingness is measured with a single item, total score during intervention 1 (EMDR or SC), intervention 2 (ET), FU1 and FU2 3. Intention to stop treatment is measured with a questionnaire, total score at T2 and T3 4. Client satisfaction is measured with the Client Satisfaction Questionnaire (CSQ-8) and Net Promotor Score (NPS), total score at T2 and T3. Adherence: 1. Session attendance rate is measured as drop out and no-show rates during intervention 2 (ET) Related symptomatology, functional impairment and quality of life: 1. General anxiety is measured with the General Anxiety Disorder 7 (GAD 7) questionnaire, total severity score at T1, T2, T3, FU1, FU2 and once weekly during the intervention phase 2. Depression is measured with the Patient Health Questionnaire (PHQ-9), total severity score at T1, T2, T3, FU1, FU2 and once weekly during the intervention phase. 3. Quality of life is measured with the EuroQol (EQ-5D), total score at T1, T2, T3, FU1, FU2 4. Adjustment is measured with the Work and Social Adjustment Scale (WSAS), total score at T1, T2, T3, FU1, FU2 |
| Overall study start date | 01/01/2020 |
| Overall study end date | 31/12/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 50 |
| Participant inclusion criteria | 1. Patients ≥18 years of age 2. Sufficient mastery of the Dutch language and ability to complete questionnaires and understand informed consent information 3. Meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for (primary) panic disorder (with or without agoraphobia) 4. Stable medication for at least 6 weeks and willingness of the patient and physician to keep medication stable during the study period (until follow up 1). The use of sedating medication (e.g., benzodiazepines) is not a contraindication, but participants are discouraged to use sedating medication before or after treatment sessions and subsequent days. Use of sedating medication will be registered. 5. The self-reported ability to refrain from alcohol or drugs 24 hours before and after each session. General use of alcohol or drugs will be discouraged. |
| Participant exclusion criteria | 1. Self-reported neurological disorder 2. Acute or recent history of suicide attempts according to the M.I.N.I. section C 3. Self-reported visual or auditory impairments that could hinder treatment 4. Self-reported epilepsy, pregnancy, or heart disease (only for the fear-conditioning task) 5. Self-reported current psychological treatment for other DSM-5 disorder 6. Not willing or able to fill in (online) questionnaires |
| Recruitment start date | 01/02/2022 |
| Recruitment end date | 01/12/2025 |
Locations
Countries of recruitment
- Netherlands
Study participating centres
Utrecht
3524 SH
Netherlands
Maastricht
6624 KD
Netherlands
Sponsor information
Research council
Winthontlaan 2
Utrecht
3526 KV
Netherlands
| Phone | +31 (0)30 6001211 |
|---|---|
| nwo@nwo.nl | |
| Website | https://www.nwo.nl/contact |
"ROR" |
https://ror.org/04jsz6e67 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Netherlands Organisation for Scientific Research, Dutch National Scientific Foundation, Dutch National Science Foundation, Dutch Research Council (Nederlandse Organisatie voor Wetenschappelijk Onderzoek), NWO:Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO), Dutch Research Council, Dutch Research Council, Netherlands, NWO
- Location
- Netherlands
Results and Publications
| Intention to publish date | 31/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The papers will be submitted for publication to (inter)national peer-reviewed scientific journals, regardless of the results, and will be made available through open access. The sponsor (NWO) requires that all publications emerging from research it funds are made available in open access immediately upon publication. Furthermore, results will be shared at national and international conferences, and be used for education and training purposes. NWO will have no influence on the publication of the results and promotes knowledge utilization. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Iris M. Engelhard (i.m.engelhard@uu.nl). Requests can be submitted by researchers with an appropriate research question and statistical analysis plan, with guarantees of privacy regulations and not interfering with publication plans of the study board. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 14/03/2023 | 16/03/2023 | Yes | No |
Editorial Notes
28/08/2024: The following changes were made:
1. The recruitment end date was changed from 01/07/2024 to 01/07/2025.
2. The overall study end date has been changed from 31/12/2024 to 31/12/2025.
3. The intention to publish date has been changed from 31/12/2024 to 31/12/2025.
03/07/2024: The recruitment end date was changed from 01/07/2024 to 01/12/2024.
05/12/2023: The following changes were made:
1. The recruitment end date was changed from 31/12/2023 to 01/07/2024.
2. The overall study end date has been changed from 01/06/2024 to 31/12/2024.
3. The intention to publish date has been changed from 01/06/2024 to 31/12/2024.
23/06/2023: Internal review.
16/03/2023: Publication reference added.
20/02/2023: The ethics approval and trial website were updated. The target number of participants was changed from 98 to 50.
09/06/2022: Trial's existence confirmed by the Medical Research Ethics Committee UMC Utrecht.
