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

  • End date
    May 9, 2025
  • participants needed
  • sponsor
    University of Texas at Austin
Updated on 4 October 2022
panic disorder
traumatic stress disorder
traumatic disorder


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.


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.

Condition Anxiety Disorders, Trauma, Generalized Anxiety Disorder, Panic Disorder, Agoraphobia, Illness Anxiety Disorder, Social Anxiety Disorder, Posttraumatic Stress Disorder, Acute Stress Disorder, Adjustment Disorder With Anxious Mood
Treatment Interoceptive Exposure, Psycho-education, Capnometry-Guided Respiratory Intervention
Clinical Study IdentifierNCT05427708
SponsorUniversity of Texas at Austin
Last Modified on4 October 2022


Yes No Not Sure

Inclusion Criteria

Clinically elevated anxiety as indicated by an eight or higher on the Overall Anxiety Severity and Impairment Scale (OASIS)
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
Social Anxiety Disorder
Posttraumatic Stress Disorder
Acute Stress Disorder
Adjustment Disorder with primary anxious mood
No current use of psychotropic medications or stable on current medications for at
least 3 months
Age 18+
Able to arrange transportation to our laboratory for study appointments

Exclusion Criteria

No history of medical conditions that would contraindicate participation in fear-provocation or respiratory challenges, including
Cardiovascular or respiratory disorders
High blood pressure
History of fainting
Pregnant or lactating
Not currently receiving other psychological treatment for anxiety
No history of a suicide attempt within the past 6 months
No history of psychosis within the past 6 months
No history of alcohol or substance use disorder (with the exception of nicotine) within the past 3 months
Does not endorse COVID-19 symptoms during the screening phase
Clear my responses

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