An interventional study of Exposure-Based Therapy in Obsessive-Compulsive Disorder, Post Traumatic Stress Disorder and Generalized Anxiety Disorder, sponsored by Jasper A. Smits. Recruiting at 2 sites in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-06-10.
Sponsored by Jasper A. Smits · Not applicable, Interventional, and Treatment
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?"
Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive-compulsive and trauma- and stressor-related disorders. However, many patients fail to respond or achieve remission with exposure-based therapy, resulting in prolonged suffering, loss of productivity, and poorly used resources. Making available a biomarker assay that can aid clinicians and patients in treatment selection has the potential to have considerable public health impact.
Basic research on fear extinction--a core mechanism of action of exposure-based therapy--may inform the development of a biomarker for the selection (yes/no) of exposure-based therapy. Growing evidence links orexin system activity to deficits in fear extinction. Our group has demonstrated that reactivity to CO2 challenge, which is a safe, affordable and easy-to-implement procedure, can serve as a proxy for orexin system activity and predicts fear extinction deficits in rodents.
Building upon this basic research, the goal for the proposed study is to validate CO2 reactivity as a biomarker of exposure-based therapy non-response. To this end, we will assess CO2 reactivity in 600 adults meeting for one or more fear- or anxiety-related disorders prior to providing open, state-of-the art, transdiagnostic exposure-based therapy. By incorporating CO2 reactivity into a multivariable model predicting treatment non-response that also includes reactivity to hyperventilation as well as a number of related and theoretically-relevant prognostic variables, we will establish the mechanistic specificity and the additive predictive value of the putative biomarker. By developing models independently within two study sites and predicting the other site's data, we will validate that the results are likely to generalize to future clinical samples.
The proposed study represents a necessary stage in translating basic research to strategies for treatment selection. The investigation addresses an important public health issue by testing an accessible clinical assessment strategy--informed by basic research--that may lead to a more effective treatment selection (personalized medicine) for patients with anxiety- and fear-related disorders and enhance our understanding of the mechanisms governing exposure-based therapy.
635 studies on the registry are indexed under Obsessive-Compulsive Disorder; 166 are open to participants now.
This study's planned enrollment of 600 is above the median of 45 across 520 interventional studies indexed under Obsessive-Compulsive Disorder.
Browse Obsessive-Compulsive Disorder studies →Jasper A. Smits is the lead sponsor of 11 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All participants will receive a well-established psychological treatment.
Behavioral: Exposure-Based Therapy
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".
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.
Time frame: Week 13 (post-treatment)
Clinical Global Impression - Severity of Illness (CGI-S)
A 7 point widely used clinician rating scale for indexing the how mentally ill a patient is at the time using a 7 point scale ranging from 1(normal, not at all ill); 2 (borderline mentally ill); 3 (mildly ill); 4 (moderately ill); 5 (markedly ill); 6 (severely ill); 7(among the most extremely ill patients).
Time frame: Weekly for 14 weeks + follow-up after 24 weeks
Overall Anxiety Severity and Impairment Scale (OASIS)
The OASIS is a self-report rating scale that comprises five items to assess the frequency and severity of anxiety, avoidance, work/school/home interference, and social interference due to anxiety. Participants select among five different response options for each item, which are coded 0-4 and are summed to obtain a total score (0-20).
Time frame: Weekly for 14 weeks + follow-up after 24 weeks
GAD-7
For participants with generalized anxiety disorder (GAD) as their primary DSM-V diagnosis, intended to assess the severity of participant symptoms. Ranged from 0 to 21, with higher scores indicating more severe distress and impairment.
Time frame: Weekly for 14 weeks + follow-up after 24 weeks
Panic Disorder Severity Scale (PDSS)
For participants with panic disorder (PD) as their primary DSM-V diagnosis, intended to assess the severity of participant symptoms. Ranged from 0 to 28, with higher scores indicating more severe distress and impairment.
Time frame: Weekly for 14 weeks + follow-up after 24 weeks
Social Phobia Inventory (SPIN)
For participants with social anxiety disorder (SAD) as their primary DSM-V diagnosis, intended to assess the severity of participant symptoms. Ranged from 0 to 68, with higher scores indicating more severe distress and impairment.
Time frame: Weekly for 14 weeks + follow-up after 24 weeks
Dimensional Obsessive-Compulsive Scale (DOCS)
For participants with obsessive compulsive disorder (OCD) as their primary DSM-V diagnosis, intended to assess the severity of participant symptoms. Ranged from 0 to 80, with higher scores indicating more severe distress and impairment.
Time frame: Weekly for 14 weeks + follow-up after 24 weeks
PTSD Checklist for DSM-5 (PCL-5)
For participants with post-traumatic stress disorder (PTSD) as their primary DSM-V diagnosis, intended to assess the severity of participant symptoms. Ranged from 0 to 80, with higher scores indicating more severe distress and impairment.
Time frame: Weekly for 14 weeks + follow-up after 24 weeks
Plan to share: Yes — In line with National Institute of Mental Health (NIMH) guidance, we will share de-identified data derived from this study via the National Data Archive (NDA), along with supporting documentation to enable efficient and appropriate use of the data. Data sharing is now a requirement for all NIMH-funded awards (NOT-MH-14-015). Consistent with the National Database for Clinical Trials related to Mental Illness (NDCT) guidelines, we will share data in a two-tiered approach. The first tier involves semi-annual uploading of descriptive and raw data while the study is ongoing, including data from standard assessments, standard clinical measures, demographic data, and raw behavioral data. The second tier includes analyzed data that result from publications. We will ensure that submitted data will conform to relevant data and terminology standards. Throughout our resource sharing plan, we will comply with NDCT guidelines.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, 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.
Data sharing details ↗ · nda.nih.gov
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
No contact was published for this record. The registry link below has the sponsor’s details.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Obsessive-Compulsive Disorder →
Jasper A. Smits