Respiratory Training vs Interoceptive Exposure in the Treatment of Transdiagnostic Pathological Anxiety

Anxiety Disorders Clinical Trial

Official title:

Respiratory Training vs Interoceptive Exposure in the Treatment of Transdiagnostic Pathological Anxiety: A Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05427708
• Other study ID #: STUDY00002306
• Status: Recruiting
• Phase: N/A
• Start date: August 22, 2022
• Est. completion date: May 2025

Study information

• Verified date: November 2023
• Source: University of Texas at Austin
• Contact: Michael J Telch, PhD
• Phone: 512-814-5480
• Email: telch[@]austin.utexas.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Purpose of the Research: The primary aim of the proposed study is to conduct a randomized parallel-group 3-arm clinical trial comparing two mechanistically distinct interventions for pathological anxiety - (1) Interoceptive Exposure (IE) utilizing graduated exposure to somatic cues (respiratory, cardiac, vestibular) with the primary aim of reducing fear responding to the presence of interoceptive perturbations; (2) Capnometry-Guided Respiratory Intervention (CGRI) aimed at raising end-tidal CO2 levels thereby lowering hyperventilation-induced respiratory alkalosis and its associated fear-eliciting somatic reactions; and (3) Psycho-education about anxiety and its effects (PsyEd), which will serve as a credible control comparator.

Description:

Anxiety sensitivity - the tendency to perceive anxiety as threatening - is a widely recognized risk factor for the development of panic disorder and other anxiety-related psychopathology. Interoceptive exposure therapy consisting of repeated exposure to interoceptive cues using respiratory provocation challenges such as hyperventilation and inhalation of various concentrations of CO2-enriched air have shown promise in reducing AS and are often included in cognitive-behavioral treatments of panic disorder with or without agoraphobia.However, some patients are unwilling to undergo exposure-based treatments, while others who do show only partial response or subsequent relapse.

Alternatively, low end-tidal CO2 (ETCO2), which is an accompanying feature of hyperventilation, has been associated with a variety of anxiety disorders, including panic disorder and social phobia. More recently, researchers have examined the efficacy of capnometry-guided respiratory intervention (CGRI) as a method for increasing ETCO2 and thereby reducing hyperventilation-induced anxiety/panic symptoms. Promising preliminary efficacy studies have shown that CGRI results in decreased panic symptom frequency and severity at a rate comparable to that of cognitive therapy. A recent uncontrolled proof-of-concept study showed that CGRI led to significant reductions in trauma symptoms in a sample of patients meeting DSM-5 criteria for PTSD. However, neither IE or CGRI has been adequately evaluated in the treatment of anxiety disorders other than panic disorder with or without agoraphobia.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Clinically elevated anxiety as indicated by an eight or higher on the Overall Anxiety Severity and Impairment Scale (OASIS).

2. Meets DSM-5 criteria for one or more of the following anxiety or trauma-related disorders as their "primary" mental disorder:

• Generalized Anxiety Disorder

• Panic Disorder

• Health Anxiety

• Agoraphobia

• Social Anxiety Disorder

• Posttraumatic Stress Disorder

• Acute Stress Disorder

• Adjustment Disorder with primary anxious mood

• Anxiety disorder not otherwise specified

3. No current use of psychotropic medications or stable on current medications for at least 6 weeks

4. Age 18+.

5. Able to arrange transportation to our laboratory for study appointments.

6. Fluent in English.

Exclusion Criteria:

1. No history of medical conditions that would contraindicate participation in fear-provocation or respiratory challenges, including:

• Cardiovascular or respiratory disorders

• High blood pressure

• Epilepsy

• Strokes

• Seizures

• History of fainting

• Pregnant or lactating

2. Not currently receiving other psychological treatment for anxiety.

3. No history of a suicide attempt within the past 6 months.

4. No history of psychosis within the past 6 months.

5. No history of moderate to severe alcohol or substance use disorder (with the exception of nicotine) within the past 3 months.

6. Does not endorse COVID-19 symptoms during the screening phase.

Related Conditions & MeSH terms

• Acute Stress Disorder
• Adjustment Disorder With Anxious Mood
• Adjustment Disorders
• Agoraphobia
• Anxiety Disorders
• Generalized Anxiety Disorder
• Illness Anxiety Disorder
• Panic Disorder
• Phobia, Social
• Posttraumatic Stress Disorder
• Social Anxiety Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic
• Stress Disorders, Traumatic, Acute
• Trauma

Intervention

Behavioral:
• Interoceptive Exposure
See: Arm/group descriptions

Device:
• Capnometry-Guided Respiratory Intervention
See: Arm/group descriptions

Behavioral:
• Psycho-Education
See: Arm/group descriptions

Locations

Country	Name	City	State
United States	University of Texas at Austin	Austin	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas at Austin	Freespira, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (18)

Beck JG, Shipherd JC, Zebb BJ. How does interoceptive exposure for panic disorder work? An uncontrolled case study. J Anxiety Disord. 1997 Sep-Oct;11(5):541-56. doi: 10.1016/s0887-6185(97)00030-3. — View Citation

Cobb AR, Lancaster CL, Meyer EC, Lee HJ, Telch MJ. Pre-deployment trait anxiety, anxiety sensitivity and experiential avoidance predict war-zone stress-evoked psychopathology. Journal of Contextual Behavioral Science. 2017;6(3):276-287.

Craske MG, Barlow DH. Mastery of Your Anxiety and Panic: Therapist Guide. Published online 2006. doi:10.1093/med:psych/9780195311402.001.0001

Kaplan A, Mannarino AP, Nickell PV. Evaluating the Impact of Freespira on Panic Disorder Patients' Health Outcomes and Healthcare Costs within the Allegheny Health Network. Appl Psychophysiol Biofeedback. 2020 Sep;45(3):175-181. doi: 10.1007/s10484-020-09465-0. — View Citation

Ley R. Blood, breath, and fears: A hyperventilation theory of panic attacks and agoraphobia. Clin Psychol Rev. 1985;5(4):271-285.

Li W, Zinbarg RE. Anxiety sensitivity and panic attacks: a 1-year longitudinal study. Behav Modif. 2007 Mar;31(2):145-61. doi: 10.1177/0145445506296969. — View Citation

Maller RG, Reiss S. Anxiety sensitivity in 1984 and panic attacks in 1987. J Anxiety Disord. 1992;6(3):241-247.

Margraf J, Barlow DH, Clark DM, Telch MJ. Psychological treatment of panic: work in progress on outcome, active ingredients, and follow-up. Behav Res Ther. 1993 Jan;31(1):1-8. doi: 10.1016/0005-7967(93)90036-t. — View Citation

Meuret AE, Rosenfield D, Seidel A, Bhaskara L, Hofmann SG. Respiratory and cognitive mediators of treatment change in panic disorder: evidence for intervention specificity. J Consult Clin Psychol. 2010 Oct;78(5):691-704. doi: 10.1037/a0019552. — View Citation

Meuret AE, Wilhelm FH, Ritz T, Roth WT. Feedback of end-tidal pCO2 as a therapeutic approach for panic disorder. J Psychiatr Res. 2008 Jun;42(7):560-8. doi: 10.1016/j.jpsychires.2007.06.005. Epub 2007 Aug 3. — View Citation

Ostacher MJ, Fischer E, Bowen ER, Lyu J, Robbins DJ, Suppes T. Investigation of a Capnometry Guided Respiratory Intervention in the Treatment of Posttraumatic Stress Disorder. Appl Psychophysiol Biofeedback. 2021 Dec;46(4):367-376. doi: 10.1007/s10484-021-09521-3. — View Citation

Reiss S, Peterson RA, Gursky DM, McNally RJ. Anxiety sensitivity, anxiety frequency and the prediction of fearfulness. Behav Res Ther. 1986;24(1):1-8. doi: 10.1016/0005-7967(86)90143-9. No abstract available. — View Citation

Schmidt NB, Lerew DR, Jackson RJ. Prospective evaluation of anxiety sensitivity in the pathogenesis of panic: replication and extension. J Abnorm Psychol. 1999 Aug;108(3):532-7. doi: 10.1037//0021-843x.108.3.532. — View Citation

Schmidt NB, Telch MJ. Role of fear of fear and safety information in moderating the effects of voluntary hyperventilation. Behav Ther. 1994;25(2):197-208.

Studer RK, Danuser B, Hildebrandt H, Arial M, Wild P, Gomez P. Hyperventilation in anticipatory music performance anxiety. Psychosom Med. 2012 Sep;74(7):773-82. doi: 10.1097/PSY.0b013e31825e3578. Epub 2012 Jul 23. — View Citation

Telch MJ, Lucas JA, Schmidt NB, Hanna HH, LaNae Jaimez T, Lucas RA. Group cognitive-behavioral treatment of panic disorder. Behav Res Ther. 1993 Mar;31(3):279-87. doi: 10.1016/0005-7967(93)90026-q. — View Citation

Telch MJ, Rosenfield D, Lee HJ, Pai A. Emotional reactivity to a single inhalation of 35% carbon dioxide and its association with later symptoms of posttraumatic stress disorder and anxiety in soldiers deployed to Iraq. Arch Gen Psychiatry. 2012 Nov;69(11):1161-8. doi: 10.1001/archgenpsychiatry.2012.8. — View Citation

Tolin DF, McGrath PB, Hale LR, Weiner DN, Gueorguieva R. A Multisite Benchmarking Trial of Capnometry Guided Respiratory Intervention for Panic Disorder in Naturalistic Treatment Settings. Appl Psychophysiol Biofeedback. 2017 Mar;42(1):51-58. doi: 10.1007/s10484-017-9354-4. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Anxiety Severity and Impairment Scale	Change from baseline in self-reported transdiagnostic anxiety symptoms (range = 0 - 20, with higher scores indexing more symptoms).	Pre-Treatment (Week 0), Post-treatment (Week 5), 2-Month Follow-Up (Week 13)
Primary	Computerized Hamilton Anxiety Scale	Change from baseline in anxiety symptom severity. Each item is assessed both in terms of frequency and severity. Scores on these probes are summed and divided by the number of response options. Higher scores index higher severity.	Pre-Treatment (Week 0), Post-treatment (Week 5), 2-Month Follow-Up (Week 13)
Secondary	Sheehan Disability Scale	Change from baseline in overall disability (range = 0 - 30, with higher scores indexing more disability).	Pre-Treatment (Week 0), Weekly Assessments (Weeks 1 - 4), Post-treatment (Week 5), 2-Month Follow-Up (Week 13)
Secondary	PROMIS - Global Health (Mental Health Subdomain)	Change from baseline in quality of life (range = 4 - 20, with higher scores indexing higher quality of life).	Pre-Treatment (Week 0), Weekly Assessments (Weeks 1 - 4), Post-treatment (Week 5), 2-Month Follow-Up (Week 13)
Secondary	Anxiety Sensitivity Composite Measure	This composite measure will incorporate scores on the Anxiety Sensitivity Index-3 (ASI-3), Body Sensations Questionnaire (BSQ), and Texas Multi-Factor Anxiety Sensitivity Scale (TMASS). Scores on each of these individual measures will be transformed into z scores and then averaged to derive this composite index. We will measure change from baseline in anxiety sensitivity.	Pre-Treatment (Week 0), Weekly Assessments (Weeks 1 - 4), Post-treatment (Week 5), 2-Month Follow-Up (Week 13)
Secondary	Modified DIAMOND	Change from baseline in DIAMOND Diagnostic Interview + Health Anxiety Questionnaire scores.	Pre-Treatment (Week 0), 2-Month Follow-Up (Week 13)