Providing Tools for Effective Care and Treatment of Anxiety Disorders (PROTECT-AD)

Providing Tools for Effective Care and Treatment of Anxiety Disorders (AD): Outcomes, Mediators and Moderators of Enhanced Extinction

PROTECT-AD is a cognitive behavioral treatment study involving highly qualified psychotherapeutic centers at seven German universities.

It is our goal to further investigate and optimize existing effective treatments of anxiety disorders. In order to achieve this, the investigators want to investigate the effect of extinction learning in an "intensified" psychological intervention on treatment outcome in adults and children with anxiety disorders.

The intensified psychological intervention is characterized by a higher number of exposure trials over a short time period. In the control condition the exposure trials take place in a weekly interval, analog to standard care.

Study Overview

• Status: Completed
• Conditions: Social Anxiety Disorder; Panic Disorder; Agoraphobia; Specific Phobias
• Intervention / Treatment: Behavioral: Intensified psychological intervention; Behavioral: Standard intervention

Detailed Description

Novel preclinical research evidence suggests extinction learning as the core mechanism of action of exposure-based therapies and provides according strategies to improve the effectiveness of treatment by optimized extinction. A translational research agenda is suggested to examine whether enhanced extinction learning components derived from preclinical research, applied within an "intensified" exposure-based treatment, improves outcomes. In a multicenter randomized clinical trial, linked to mechanistic subprojects, the investigators test in n=620 patients with primary AD allowing for comorbidity whether intensified psychological interventions based on augmented extinction learning (IPI) result in faster, stronger and more persistent outcomes on subjective, clinical, behavioral, physiological and neural indices as compared to an, otherwise identical, standard research treatment without explicit enhanced extinction (TAU). The investigators hypothesize that (a) enhanced extinction elements (IPI) will result in higher effect sizes, faster recovery, (b) more pronounced changes in an array of systems, including elements of extinction learning and in objective behavioral measures assessed in intersession exposure trials. The investigators also examine moderators of outcome (i.e. type of diagnosis, comorbidity) and explore whether IPI is associated with lower health care costs.

• Study Type: Interventional
• Enrollment (Actual): 726
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Sachsen
    • Dresden, Sachsen, Germany, 01187
      • Technische Universität Dresden, Institute of Clinical Psychology and Psychotherapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 15 - 70 years
• one or more of the following DSM-IV/5 anxiety disorders: Panic Disorder, Agoraphobia, Social Anxiety Disorder, Specific Phobia
• HAMA - Score > 18
• CGI - Score > 3
• Can attend therapy regularly (with or without support)
• Informed Consent

Exclusion Criteria:

• Every reason the protocol may not be upheld (e.g. planned hospitalization within study time frame, planning to move away, etc.)
• Current suicidal tendency
• DSM-5 Bipolar Disorder
• DSM-5 Psychotic Disorder
• DSM-5 Borderline Personality Disorder
• Current treatment of other mental disorder (drugs, psychotherapy)
• Current Alcohol, Benzodiazepine or other Substance Use Disorders
• Severe medical illness/condition (every serious physical illness, including cardiovascular, kidney, endocrinological and neurological conditions, Hepatitis or other clinical findings that suggest a severe illness and may affect participation in the study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intensified Psychological Intervention; Intensified psychological intervention (Cognitive Behavioral Therapy), based on optimized extinction learning	Behavioral: Intensified psychological intervention; 12 sessions of Cognitive Behavioral Therapy a 100 minutes, over the course of 6 weeks (2 sessions per week/week 1 and 2, 3 sessions per week/week 3 und 4, 1 session per week/week 5 and 6)
ACTIVE_COMPARATOR: Treatment As Usual; Standard intervention (Cognitive Behavioral Therapy) without optimized extinction learning	Behavioral: Standard intervention; 12 sessions of Cognitive Behavioral Therapy a 100 minutes, over the course of 10 weeks (2 sessions per week/week 1 and 2, 1 session per week/week 3 to 10)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in somatic and psychic anxiety symptoms	Anxiety symptoms are assessed using the clinician-rated Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A for the HAMA). Stronger, faster and more persistent reduction of anxiety symptoms in the IPI group than in the TAU group is expected.	assessed three times: Baseline, Post (1 week after end of therapy) and Follow up (6 months after end of therapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in severity of the anxiety disorder	Severity of the anxiety disorder is assessed by the clinician-rated Clinical Global Impression Scale (CGI). It is anchored for anxiety disorders.	assessed five times: Baseline, therapy session 4 (week 2 of therapy), therapy session 11 (week 5 to week 9 of therapy), Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in categorial diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV/5)	categorical diagnoses are assessed using a German version of the Composite International Diagnostic Interview (CIDI).	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in screened anxiety symptoms	The DSM-5 cross-cutting symptom measure for anxiety disorders ("Cross-D") is used as a brief screener for anxiety symptoms.	assessed fivetimes: Baseline, therapy session 4 (week 2 of therapy), therapy session 11 (week 5 to week 9 of therapy), Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in depressive symptoms	depressive symptoms are assessed using the Beck Depression Inventory (BDI-II)	assessed fivetimes: Baseline, therapy session 4 (week 2 of therapy), therapy session 11 (week 5 to week 9 of therapy), Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in anxiety sensitivity	anxiety sensitivity is assessed using the Anxiety sensitivity inventory (ASI)	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in panic and agoraphobic symptoms	panic and agoraphobic symptoms are assessed using the Panic and agoraphobia scale (PAS)	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in agoraphobic avoidance	agoraphobic avoidance is assessed using the Mobility Inventory (MI)	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in symptoms of Generalized Anxiety Disorder	symptoms of generalized anxiety disorder (GAD)are assessed using the GAD-7	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in social anxiety	social anxiety is assessed using the Liebowitz Social Anxiety Scale (LSAS)	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in Specific Phobia symptoms	symptoms of specific phobia are assessed using an adapted version of the DSM-5 dimensional scale for specific phobias	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in disability	Disability is assessed using the 12-item version of the World Health Organization Disability Schedule (WHODAS 2.0)	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in quality of life	Quality of life is assessed using the EuroQol five-dimensional measure for quality of life (EQ5D)	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in psychopathological symptoms	psychopathological symptoms are assessed using the Brief Symptom Inventory (BSI), a short form of the Symptom Checklist 90 (SCL-90). At Baseline, Post and Follow Up, the 53 item Version is used, during therapy the 18 item version is used	assessed seven times: Baseline, therapy sessions 2 (week 1 of therapy), 4 (week 2), 7 (week 3 to 5), 10 (week 4 to 8), 11 (week 5 to 9), 12 (week 6 to 10) Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
change in agoraphobic cognitions	agoraphobic cognitions are assessed using the Agoraphobic Cognitions Questionnaire (ACQ)	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)
fear of body sensations	fear of body sensations is assessed using the Body Sensations Questionnaire (BSQ)	assessed three times: Baseline, Post (1 week after end of therapy) and Follow Up (6 months after end of therapy)

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Collaborators: Charite University, Berlin, Germany; University Medicine Greifswald; Ruhr University of Bochum; Wuerzburg University Hospital; University of Wuerzburg; Westfälische Wilhelms-Universität Münster; Philipps University Marburg Medical Center
• Investigators: Principal Investigator: Hans-Ulrich Wittchen, Ph.D., Technische Universität Dresden

Publications and helpful links

General Publications

• Heinig I, Pittig A, Richter J, Hummel K, Alt I, Dickhover K, Gamer J, Hollandt M, Koelkebeck K, Maenz A, Tennie S, Totzeck C, Yang Y, Arolt V, Deckert J, Domschke K, Fydrich T, Hamm A, Hoyer J, Kircher T, Lueken U, Margraf J, Neudeck P, Pauli P, Rief W, Schneider S, Straube B, Strohle A, Wittchen HU. Optimizing exposure-based CBT for anxiety disorders via enhanced extinction: Design and methods of a multicentre randomized clinical trial. Int J Methods Psychiatr Res. 2017 Jun;26(2):e1560. doi: 10.1002/mpr.1560. Epub 2017 Mar 21.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 12, 2015
• Primary Completion (ACTUAL): July 24, 2019
• Study Completion (ACTUAL): July 24, 2019

Study Registration Dates

• First Submitted: August 24, 2015
• First Submitted That Met QC Criteria: November 13, 2015
• First Posted (ESTIMATE): November 16, 2015

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Panic Disorder; Social Anxiety Disorder; Agoraphobia; Behavioral Therapy; Anxiety Disorders; Specific Phobia; Extinction Learning; Optimized Extinction; Massed Confrontation
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Phobic Disorders; Disease; Anxiety Disorders; Phobia, Social; Panic Disorder; Agoraphobia
• Other Study ID Numbers: 01EE1402A; DRKS00008743 (REGISTRY: German Clinical Trials Register)