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

Официальное название

Carbon Dioxide (CO2) Reactivity as a Biomarker of Non-Response to Exposure-Based Therapy

Обзор

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?"

Подробное описание

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.

Вмешательства

• Поведенческое 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 pract

Первичные конечные точки

• Non-response to exposure-based therapy [Срок оценки: Week 13 (post-treatment)]

Вторичные конечные точки (7)

• Clinical Global Impression - Severity of Illness (CGI-S) [Срок оценки: Weekly for 14 weeks + follow-up after 24 weeks]
• Overall Anxiety Severity and Impairment Scale (OASIS) [Срок оценки: Weekly for 14 weeks + follow-up after 24 weeks]
• GAD-7 [Срок оценки: Weekly for 14 weeks + follow-up after 24 weeks]
• Panic Disorder Severity Scale (PDSS) [Срок оценки: Weekly for 14 weeks + follow-up after 24 weeks]
• Social Phobia Inventory (SPIN) [Срок оценки: Weekly for 14 weeks + follow-up after 24 weeks]
• Dimensional Obsessive-Compulsive Scale (DOCS) [Срок оценки: Weekly for 14 weeks + follow-up after 24 weeks]
• PTSD Checklist for DSM-5 (PCL-5) [Срок оценки: Weekly for 14 weeks + follow-up after 24 weeks]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Boston University — Boston
• The University of Texas at Austin — Austin

Публикации

• 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

Идентификаторы

NCT: NCT05467683 · STUDY00001631 · 1R01MH125951-01A1 · 1R01MH125949-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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