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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Anxiety Disorders; Generalized Anxiety Disorder; Trauma; Posttraumatic Stress Disorder; Social Anxiety Disorder; Panic Disorder; Agoraphobia; Illness Anxiety Disorder; Acute Stress Disorder; Adjustment Disorder With Anxious Mood
• Intervention / Treatment: Behavioral: Interoceptive Exposure; Device: Capnometry-Guided Respiratory Intervention; Behavioral: Psycho-Education

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael J Telch, PhD; Phone Number: 512-814-5480; Email: telch@austin.utexas.edu
• Study Contact Backup: Name: Cate Fischer, MA; Phone Number: 512-522-6216; Email: utinterventionstudy@gmail.com

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78712
      • Recruiting
      • University of Texas at Austin
      • Contact: Michael J Telch, PhD; Phone Number: 512-814-5480; Email: telch@austin.utexas.edu
      • Contact: Cate Fischer, MA; Phone Number: 512-522-6216; Email: utinterventionstudy@gmail.com
      • Principal Investigator: Michael J Telch, PhD
      • Principal Investigator: Cate Fischer, MA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interoceptive Exposure (IE); Participants assigned to the interoceptive exposure condition will receive twice-weekly 90-minute in-person treatment sessions for four weeks. This treatment will include education about anxiety and factors that maintain anxiety symptoms. In addition, participants will be asked to perform exercises designed to activate potentially distressing - but harmless - bodily sensations that are commonly associated with stress and anxiety. Participants will also be encouraged to practice these exercises daily at home.	Behavioral: Interoceptive Exposure; See: Arm/group descriptions; Other Names: IE
Experimental: Capnometry-Guided Respiratory Intervention (CGRI); If assigned to this condition, participants will be expected to complete twice-daily 17-minute tablet-assisted breathing exercises at home for four weeks. They will also receive brief phone check-ins with their study therapist weekly to review progress and troubleshoot any problems they may be experiencing. Last, these participants will have access to a paced-breathing app that provides audio recordings to maintain specified breathing rates for up to 10 minutes.	Device: Capnometry-Guided Respiratory Intervention; See: Arm/group descriptions; Other Names: CGRI
Active Comparator: Psycho-Education (PsyEd); If assigned to the psycho-education condition, participants will undergo once-weekly 20-minute video conferencing session with a therapist for four weeks. During these sessions, they will be provided information about the nature and causes of anxiety-related disorders and learn tips for coping with anxiety symptoms when they arise. At the end of their sessions with the therapist, they will receive handouts that will help reinforce what they've learned.	Behavioral: Psycho-Education; See: Arm/group descriptions; Other Names: PsyEd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
Modified DIAMOND	Change from baseline in DIAMOND Diagnostic Interview + Health Anxiety Questionnaire scores.	Pre-Treatment (Week 0), 2-Month Follow-Up (Week 13)

Collaborators and Investigators

• Sponsor: University of Texas at Austin
• Collaborators: Freespira, Inc.

Publications and helpful links

General Publications

• 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.
• Maller RG, Reiss S. Anxiety sensitivity in 1984 and panic attacks in 1987. J Anxiety Disord. 1992;6(3):241-247.
• 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.
• 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.
• 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.
• Craske MG, Barlow DH. Mastery of Your Anxiety and Panic: Therapist Guide. Published online 2006. doi:10.1093/med:psych/9780195311402.001.0001
• Ley R. Blood, breath, and fears: A hyperventilation theory of panic attacks and agoraphobia. Clin Psychol Rev. 1985;5(4):271-285.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2022
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Intervention; Psychoeducation; Transdiagnostic; Respiratory training; Interoceptive exposure
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Phobic Disorders; Anxiety Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Phobia, Social; Panic Disorder; Agoraphobia; Adjustment Disorders; Stress Disorders, Traumatic, Acute
• Other Study ID Numbers: STUDY00002306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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