CO2 Reactivity as a Biomarker of Non-Response to Exposure-Based Therapy

NCT05467683 | Recruiting DMC

• 3 other identifiers: STUDY000016311R01MH125951-01A11R01MH125949-01A1
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 2

Brief Summary

Anxiety-, obsessive-compulsive and trauma- and stressor-related disorders reflect a significant public health problem. This study is designed to evaluate the predictive power of a novel biomarker based on a CO2 challenge, thus addressing the central question "can this easy-to-administer assay aid clinicians in deciding whether or not to initiate exposure-based therapy?"

Conditions

Obsessive-Compulsive Disorder; Post Traumatic Stress Disorder; Generalized Anxiety Disorder; Social Anxiety Disorder; Panic Disorder

Outcome Measures

Primary Outcomes (1)

• Non-response to exposure-based therapy

  Participants will be classified as non-responders if their Clinical Global Impression - Global Improvement (CGI-I) score is 3 or above OR if their Overall Anxiety Severity and Impairment Scale (OASIS) score has not improved by at least 4 points.

  Week 13 (post-treatment)

Secondary Outcomes (7)

• Clinical Global Impression - Severity of Illness (CGI-S)

  Weekly for 14 weeks + follow-up after 24 weeks

• Overall Anxiety Severity and Impairment Scale (OASIS)

  Weekly for 14 weeks + follow-up after 24 weeks

• GAD-7

  Weekly for 14 weeks + follow-up after 24 weeks

• Panic Disorder Severity Scale (PDSS)

  Weekly for 14 weeks + follow-up after 24 weeks

• Social Phobia Inventory (SPIN)

  Weekly for 14 weeks + follow-up after 24 weeks

Study Arms (1)

Open Exposure-Based Therapy (EBT)

OTHER

All participants will receive a well-established psychological treatment.

Behavioral: Exposure-Based Therapy

Interventions

Exposure-Based Therapy BEHAVIORAL

Treatment will consist of 12 one-hour sessions, delivered over the course of 12 weeks. EBT will be delivered by trained and experienced license-eligible clinicians. The study clinician will develop a personalized assessment and treatment plan for each patient. Consistent with contemporary models of EBT, exposure practice aims to help patients reestablish a sense of safety around feared cues. Hence, exposure exercises are planned to ensure violation of threat expectancies. That is, exposure practice is deemed appropriate and effective if it allows the patient to learn that what they feared would happen does not happen. Practice will occur across relevant contexts both within and outside the session (i.e., homework) and clinicians will guide patients in processing practice to facilitate the consolidation of safety learning. To achieve these ends, study clinicians will use the manual "Personalized Exposure Therapy: A Person-Centered Transdiagnostic Approach".

Open Exposure-Based Therapy (EBT)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A primary DSM-5 diagnosis of panic disorder (with or without an agoraphobia diagnosis), social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, or post-traumatic stress disorder as assessed by the Structured Clinical Interview for the DSM-5 (SCID-5)
• A score of 8 or greater on the Overall Anxiety Severity and Impairment Scale (OASIS)
• Ages 18 to 70
• Willingness and ability to provide informed consent and comply with the requirements of the study protocol.
• Proficiency in English (because assessment instruments have only been validated in English)

You may not qualify if:

• A lifetime history of bipolar or psychotic disorders, substance use disorders (other than nicotine) or eating disorder in the past 6 months; serious cognitive impairment.
• Active suicidal ideation with at least some intent to act with or without specific plan (a rating of 4 for suicidal ideation on the Columbia-Suicide Severity Rating Scale) or suicidal behaviors (actual attempt, interrupted attempt, aborted or self-interrupted attempt, or preparatory acts or behavior) within the past 6 months.
• Medical conditions contraindicating CO2 inhalation or hyperventilation challenge (e.g., cardiac arrhythmia, cardiac failure, asthma, lung fibrosis, high blood pressure, epilepsy, or stroke).
• Pregnancy or lactation
• Ongoing psychotherapy directed toward the primary disorder.
• Pharmacological treatment started within 8 weeks prior to the screen (patients "stable" on their medication regimen will be included and their medication status will be included as a variable in the model)

Sponsors & Collaborators

• Boston University: collaborator
• National Institute of Mental Health (NIMH): collaborator
• Jasper A. Smits: lead

Study Sites (2)

Boston University

Boston, Massachusetts, 02215, United States

RECRUITING

The University of Texas at Austin

Austin, Texas, 78712, United States

RECRUITING

Related Publications (1)

• Smits JAJ, Monfils MH, Otto MW, Telch MJ, Shumake J, Feinstein JS, Khalsa SS, Cobb AR, Parsons EM, Long LJ, McSpadden B, Johnson D, Greenberg A; Exposure Therapy Consortium. CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol. BMC Psychiatry. 2022 Dec 27;22(1):831. doi: 10.1186/s12888-022-04478-x.

  PMID: 36575425 DERIVED

MeSH Terms

Conditions

Obsessive-Compulsive Disorder; Stress Disorders, Post-Traumatic; Generalized Anxiety Disorder; Phobia, Social; Panic Disorder

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Phobic Disorders

Study Officials

• Jasper Smits, Ph.D.

  The University of Texas at Austin

  PRINCIPAL INVESTIGATOR

• Michael Otto, Ph.D.

  Boston University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychology

Study Record Dates

• First Submitted: June 27, 2022
• First Posted: July 20, 2022
• Study Start: November 2, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Descriptive/raw data will be shared on a semi-annual basis (on or before January 15 and July 15, beginning six months after the award budget period has begun). Analyzed data will be submitted prior to publication/public dissemination (whether the findings are positive or negative) using the NDA Study feature that links data deposited in the NDA with publications/findings.
• Access Criteria: We agree that data will be deposited and made available through NDA, and that these data will be shared with investigators working at an institution with a Federal Wide Assurance (FWA) and could be used for secondary study purposes. All submitted data (both descriptive/raw and analyzed data) will be made available for access by qualified members of the research community according to the provisions defined in the NIMH Data Repositories Data Access Agreement and Use Certification.

Locations

US (2)