Clinical trial NCT05427708: Respiratory Training vs Interoceptive Exposure in the Treatment of Transdiagnostic Pathological Anxiety
Official title: Respiratory Training vs Interoceptive Exposure in the Treatment of Transdiagnostic Pathological Anxiety: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: 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
Keywords: Psychoeducation
Respiratory training
Interoceptive exposure
Transdiagnostic
Intervention
Lead sponsor: University of Texas at Austin
Sponsor class: OTHER
Collaborators: name: Freespira, Inc.
First posted: 2022-06-22
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study will utilize a 3 x 3 randomized controlled trial design with intervention type as a between-subjects factor with three levels (IE, CGRI, PsyEd) and time points (baseline, posttreatment, 2-month follow-up) as a three-level within-subjects factor.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Anxiety Severity and Impairment Scale
timeFrame: Pre-Treatment (Week 0), Post-treatment (Week 5), 2-Month Follow-Up (Week 13)
measure: Computerized Hamilton Anxiety Scale
timeFrame: Pre-Treatment (Week 0), Post-treatment (Week 5), 2-Month Follow-Up (Week 13)
Secondary outcomes:
measure: Sheehan Disability Scale
timeFrame: Pre-Treatment (Week 0), Weekly Assessments (Weeks 1 - 4), Post-treatment (Week 5), 2-Month Follow-Up (Week 13)
measure: PROMIS - Global Health (Mental Health Subdomain)
timeFrame: Pre-Treatment (Week 0), Weekly Assessments (Weeks 1 - 4), Post-treatment (Week 5), 2-Month Follow-Up (Week 13)
measure: Anxiety Sensitivity Composite Measure
timeFrame: Pre-Treatment (Week 0), Weekly Assessments (Weeks 1 - 4), Post-treatment (Week 5), 2-Month Follow-Up (Week 13)
measure: Modified DIAMOND
timeFrame: Pre-Treatment (Week 0), 2-Month Follow-Up (Week 13)
Other outcomes:
Locations:
city: Austin
country: United States
facility: University of Texas at Austin
state: Texas
Study officials:
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