Clinical trial NCT01323556: Mechanisms of Panic Disorders Treatment
Official title: Mechanisms of CBT-Treatment Effects in Patients With Panic Disorder and Panic Disorder With Agoraphobia: The Role of Interoceptive Exposure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Panic Disorder
Agoraphobia
Panic Attacks
Keywords: Panic disorder
agoraphobia
panic attacks
exposure based learning
interoceptive exposure exercises
fear augmentation
in vivo exposure
Lead sponsor: University Medicine Greifswald
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
First posted: 2011-03-25
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Investigation of mechanisms of exposure based learning by

1. Investigating the effects of fear augmentation by interoceptive exposure during in vivo exposure
2. Disentangling the effects of interoceptive exposure exercises in panic disorder

Detailed description: The study aims on investigating the effect of fear augmentation during in-vivo exposure by adding interoceptive exposure (e.g., hyperventilation) in PD/AG patients. By comparing the fear augmentation group with the therapist-guided CBT exposure, and by measuring autonomic arousal during and between exposure sessions, it will be possible to study the mechanisms of exposure based learning. A second aim is to disentangle effects of specific interoceptive exposure exercises (e.g., respiratory vs. vestibular stimulation). Finally, by including patients without agoraphobic avoidance it will be possible to investigate whether interoceptive exposure alone will have any effect. This might open the door for early interventions for individuals after experiencing an initial panic attack to prevent the development of a severe panic disorder with agoraphobic avoidance.

Eligibility criteria: Inclusion Criteria:

* Age 18-65 years old
* Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of panic disorder, panic disorder with agoraphobia OR initial panic attacks
* CGI ≥ 4 (except persons with initial panic attacks)
* Informed Consent

Exclusion Criteria:

* Acute suicidality
* Current substance use disorder
* Lifetime diagnosis of psychotic disorders, bipolar disorders, borderline personality disorders
* Severe medical condition (chronic conditions)
* Current psychotherapeutic or psychopharmacological treatment

Primary outcomes:
measure: Hamilton Anxiety Rating Scale (HARS)
timeFrame: up to 32 weeks (follow up)
measure: Clinician Global Impression Scale (CGI)
timeFrame: up to 32 weeks (follow up)
measure: Panic and Agoraphobia Scale (PAS)
timeFrame: up to 32 weeks (follow up)
measure: Mobility Inventory
timeFrame: up to 32 weeks (follow up)
measure: Number of panic attacks
timeFrame: up to 32 weeks (follow up)
Secondary outcomes:
Other outcomes:
Locations:
city: Greifswald
country: Germany
facility: Prof. Dr. Alfons Hamm
Study officials:
affiliation: Institute for Psychology Ernst-Moritz-Arndt-University Greifswald Franz-Mehring-Str. 47; 17487 Greifswald, Germany
name: Alfons O. Hamm, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Clinical Psychology and Rehabilitation/ Christoph-Dornier-Foundation for Clinical Psychology University Bremen Grazer Str. 2b 28359 Bremen, Germany
name: Thomas Lang, Dr.
role: STUDY_DIRECTOR
affiliation: Institute for Clinical Psychology and Psychotherapy WWU Münster Fliednerstr. 21 48149 Münster, Germany
name: Alexander L. Gerlach, Prof. Dr.
role: STUDY_CHAIR
affiliation: Department of Psychiatry und Psychotherapy Philipps-University Marburg Rudolf-Bultmann- Straße 8 35039 Marburg, Germany
name: Tilo Kirchner, Prof. Dr.
role: STUDY_CHAIR
affiliation: Institute for Biological Psychology, Clinical Psychology and Psychotherapy University Würzburg Marcusstrasse 9-11 97070 Würzburg, Germany
name: Georg W. Alpers, Prof. Dr.
role: STUDY_CHAIR
References:
citation: Kunas SL, Hilbert K, Yang Y, Richter J, Hamm A, Wittmann A, Strohle A, Pfleiderer B, Herrmann MJ, Lang T, Lotze M, Deckert J, Arolt V, Wittchen HU, Straube B, Kircher T, Gerlach AL, Lueken U. The modulating impact of cigarette smoking on brain structure in panic disorder: a voxel-based morphometry study. Soc Cogn Affect Neurosci. 2020 Oct 8;15(8):849-859. doi: 10.1093/scan/nsaa103.
citation: Yang Y, Lueken U, Richter J, Hamm A, Wittmann A, Konrad C, Strohle A, Pfleiderer B, Herrmann MJ, Lang T, Lotze M, Deckert J, Arolt V, Wittchen HU, Straube B, Kircher T. Effect of CBT on Biased Semantic Network in Panic Disorder: A Multicenter fMRI Study Using Semantic Priming. Am J Psychiatry. 2020 Mar 1;177(3):254-264. doi: 10.1176/appi.ajp.2019.19020202. Epub 2019 Dec 16.
citation: Gechter J, Liebscher C, Geiger MJ, Wittmann A, Schlagenhauf F, Lueken U, Wittchen HU, Pfleiderer B, Arolt V, Kircher T, Straube B, Deckert J, Weber H, Herrmann MJ, Reif A, Domschke K, Strohle A. Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls. Neuroimage Clin. 2019;24:102029. doi: 10.1016/j.nicl.2019.102029. Epub 2019 Oct 21.
citation: Forstner AJ, Awasthi S, Wolf C, Maron E, Erhardt A, Czamara D, Eriksson E, Lavebratt C, Allgulander C, Friedrich N, Becker J, Hecker J, Rambau S, Conrad R, Geiser F, McMahon FJ, Moebus S, Hess T, Buerfent BC, Hoffmann P, Herms S, Heilmann-Heimbach S, Kockum I, Olsson T, Alfredsson L, Weber H, Alpers GW, Arolt V, Fehm L, Fydrich T, Gerlach AL, Hamm A, Kircher T, Pane-Farre CA, Pauli P, Rief W, Strohle A, Plag J, Lang T, Wittchen HU, Mattheisen M, Meier S, Metspalu A, Domschke K, Reif A, Hovatta I, Lindefors N, Andersson E, Schalling M, Mbarek H, Milaneschi Y, de Geus EJC, Boomsma DI, Penninx BWJH, Thorgeirsson TE, Steinberg S, Stefansson K, Stefansson H, Muller-Myhsok B, Hansen TF, Borglum AD, Werge T, Mortensen PB, Nordentoft M, Hougaard DM, Hultman CM, Sullivan PF, Nothen MM, Woldbye DPD, Mors O, Binder EB, Ruck C, Ripke S, Deckert J, Schumacher J. Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression. Mol Psychiatry. 2021 Aug;26(8):4179-4190. doi: 10.1038/s41380-019-0590-2. Epub 2019 Nov 11.
citation: Gottschalk MG, Richter J, Ziegler C, Schiele MA, Mann J, Geiger MJ, Schartner C, Homola GA, Alpers GW, Buchel C, Fehm L, Fydrich T, Gerlach AL, Gloster AT, Helbig-Lang S, Kalisch R, Kircher T, Lang T, Lonsdorf TB, Pane-Farre CA, Strohle A, Weber H, Zwanzger P, Arolt V, Romanos M, Wittchen HU, Hamm A, Pauli P, Reif A, Deckert J, Neufang S, Hofler M, Domschke K. Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes. Transl Psychiatry. 2019 Feb 4;9(1):75. doi: 10.1038/s41398-019-0415-8.
citation: Hommers LG, Richter J, Yang Y, Raab A, Baumann C, Lang K, Schiele MA, Weber H, Wittmann A, Wolf C, Alpers GW, Arolt V, Domschke K, Fehm L, Fydrich T, Gerlach A, Gloster AT, Hamm AO, Helbig-Lang S, Kircher T, Lang T, Pane-Farre CA, Pauli P, Pfleiderer B, Reif A, Romanos M, Straube B, Strohle A, Wittchen HU, Frantz S, Ertl G, Lohse MJ, Lueken U, Deckert J. A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety. Transl Psychiatry. 2018 Oct 19;8(1):226. doi: 10.1038/s41398-018-0278-4.
citation: Weck F, Grikscheit F, Hofling V, Kordt A, Hamm AO, Gerlach AL, Alpers GW, Arolt V, Kircher T, Pauli P, Rief W, Lang T. The role of treatment delivery factors in exposure-based cognitive behavioral therapy for panic disorder with agoraphobia. J Anxiety Disord. 2016 Aug;42:10-8. doi: 10.1016/j.janxdis.2016.05.007. Epub 2016 May 13.
citation: Hamm AO, Richter J, Pane-Farre C, Westphal D, Wittchen HU, Vossbeck-Elsebusch AN, Gerlach AL, Gloster AT, Strohle A, Lang T, Kircher T, Gerdes AB, Alpers GW, Reif A, Deckert J. Panic disorder with agoraphobia from a behavioral neuroscience perspective: Applying the research principles formulated by the Research Domain Criteria (RDoC) initiative. Psychophysiology. 2016 Mar;53(3):312-22. doi: 10.1111/psyp.12553.