Threat Interpretation Bias as Cognitive Marker and Treatment Target in Pediatric Anxiety: R33 Phase
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Change in Linguistic Interpretation Bias as Assessed by the Word-sentence Association Paradigm for Youth (WSAP-Y)
研究概览
简要总结
Anxiety is chronic, debilitating, and the most common mental health problem across development, costing the U.S. over $42 billion annually. This phased innovation grant will test a symptom-personalized cognitive bias modification for interpretation bias (CBM-I) as a mechanistic intervention to reduce interpretation bias and, subsequently, anxiety, in clinically anxious youth. In this R33 trial, participants will be youth ages 10 to 17 (N=72) with a primary "big three" anxiety disorder (i.e., Generalized, Separation, Social). Youth will be randomly assigned to receive either 16 sessions of personalized CBM-I (the optimal dose identified in the R61 Phase of this study) or equivalent time (four one-hour sessions) over four weeks of a cognitive restructuring (CR), intervention. Both interventions aim to modify threat-focused thinking. Please note that the first phase of the trial (R61: NCT04245501 under NIMH award R61MH121552) has been completed and currently this record summary only reflects the R33 phase.
详细描述
Anxiety is chronic, debilitating, and the most common mental health problem across development, costing the U.S. over $42 billion annually. As anxiety disorders most commonly onset before age 18, the period from childhood through adolescence offers a critical window within which to intervene. Unfortunately, evidence-based interventions are costly, not widely available, and ineffective for upwards of 50% of youth. In response, pediatric anxiety experts and the National Institute of Mental Health (NIMH) have called for approaches that directly target underlying mechanisms to improve treatments for anxious youth. One such putative mechanism is interpretation bias - the appraisal of environmental ambiguity as threatening. Interpretation bias has been identified as a mechanism underlying the development and maintenance of youth anxiety. We have found that interpretation bias for threat, objectively measured with a paradigm that assesses whether and how quickly youth respond to ambiguous stimuli with threatening appraisals, occurs in 90% of clinically anxious youth, predicts anxiety severity above and beyond clinical characteristics, and differentiates anxious from non-anxious youth. CBM-I is a computerized intervention that attempts to reduce anxiety by directly targeting and reducing interpretation bias. While findings in the child literature are preliminary, studies with adults provide initial support that CBM-I at high dose (i.e., more than a few trainings) may reduce anxiety. This phased innovation grant tests personalized CBM-I in youth ages 10 to 17 who meet diagnostic criteria for a primary anxiety disorder (Generalized, Separation, Social). In the previous R61 Phase (N=50), a randomized clinical trial (RCT) examined whether CBM-I personalized to youth anxiety symptoms significantly reduced interpretation bias compared to a computerized interpretation control condition (ICC) and identified the optimal dose for reduction in interpretation bias. The R61 trial results indicated that CBM-I outperforms ICC on interpretation bias reduction, so the current R33 phase will proceed. In this R33 Phase, an RCT (N=72) will validate whether CBM-I significantly reduces interpretation bias, and conducts a mechanism test (i.e., does bias reduction precede and predict anxiety reduction?), by comparing CBM-I to CR, a clinically relevant psychosocial intervention that also targets anxious cognition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of signed and dated informed consent form by parent/legal guardian and signed youth assent. If youth turns 18 after study entry (i.e., Visit 1), they will need to reconsent as an adult to continue participation. Youth and consenting parent/legal guardian agree to 6-week study participation as part of consent/assent process.
- •Youth and parent/legal guardian speak sufficient English to engage in study procedures.
- •Youth is aged 10 to 17 inclusive, at time of signing consent/assent and completion of Visit 1 procedures.
- •Youth meets full diagnostic criteria for primary Generalized Anxiety Disorder, Separation Anxiety Disorder, or Social Anxiety Disorder as assessed by the Anxiety Disorders Interview Schedule-IV (ADIS-IV) during Visit
- •Note: the ADIS diagnostic criteria are only valid for two weeks. For the purposes of our study, a youth should be randomized, have randomization revealed, and be in treatment (i.e., complete Visit 2) within 14 days of Visit 1 diagnostic/clinical interview. If this timeline is not met, clinical measures may need to be updated with the youth and parent/legal guardian, although consent does not need to be re-obtained. Parent and youth versions of the Screen for Child Anxiety Related Emotional Disorders, as well as the Pediatric Anxiety Rating Scale and Clinician's Global Impressions - Severity/Improvement Scale might also be re-administered. The ADIS will need to be reviewed to assess whether there have been any diagnostic changes during the elapsed time period. If more than one month has elapsed from the time of baseline, all measures within baseline procedures would be readministered, including reconsenting parent/legal guardian and youth. All such cases must be triaged in the next immediate weekly Project Management meeting.
- •Youth otherwise meeting study entry criteria, who are receiving treatment for a stable medical or psychiatric condition, may be included providing that medication and dose have been stable for at least six weeks (e.g., stable dose of stimulant medication for Attention-Deficit/Hyperactivity Disorder) prior to study entry and remain stable on that medication and dose throughout their study participation. Changes to medication during study participation following randomization at Visit 2 will be considered non-urgent protocol deviations and will be tracked in the Protocol Deviations Form. Youth would not be removed from the study in this case, but their data may be excluded from sensitivity analyses.
- •Youth must have a standard score of at least 85 on the Wechsler Abbreviated Scale of Intelligence, Vocabulary and Matrix Reasoning subtests, as well as the Wide Range Achievement Test-4 Reading subtest (administered during Visit 1) to ensure ability to read and understand stimuli during interpretation bias assessments and CBM-I.
- •Youth must have access to a desktop or laptop computer and access to internet at home or can access one at their school or local library for the at-home portion of the computer training program. For youth without access, families can agree to complete all 16 CBM-I trainings (if randomized to CBM-I) at the BRAVE Lab.
排除标准
- •Requires treatment other than CBM-I/CR: namely, youths with severe anxiety indicating need for higher level of care (e.g., psychiatric hospitalization), or primary major depressive disorder, bipolar disorder, psychosis, safety concerns due to recent or current acute suicidal ideation with plan, intent, and/or attempt that warrants alternate intervention, Posttraumatic Stress Disorder, substance dependence, current physical or sexual abuse, or intellectual disability. This will be determined during the Visit 1 ADIS interview. Consultation with the PI will occur in all cases where another mental health concern may be primary and/or warrant more immediate treatment.
- •At Visit 1, is currently in alternate psychosocial intervention for any reason or has plans to initiate any psychosocial intervention for any reason.
- •Has previously received any type of cognitive bias modification (attention or interpretation bias as target) at the BRAVE Lab or elsewhere.
- •The family indicates they are no longer interested or able to participate in the study after Visit 1 (in which it is determined that the family is eligible) but before the family is randomized or told of their randomization. The youth will be excluded and not included in ITT analyses, and the randomization will be "thrown back" into the randomization scheme.
- •Has significant uncorrected vision impairment (e.g., uncorrected blindness) that precludes participation in the computerized assessment and intervention components of the study.
研究组 & 干预措施
Cognitive Bias Modification for Interpretations (CBM-I)
Computerized 16-session intervention aimed at reducing interpretation bias. In this study, CBM-I is personalized to youth anxiety symptoms. During CBM-I sessions, youth indicate whether word-sentence pairs are related, and are provided with feedback aimed to reduce bias.
干预措施: Cognitive Bias Modification for Interpretations (CBM-I) (Other)
Cognitive Restructuring (CR)
Four session psychosocial intervention aimed at reducing anxiety. CR is a standard treatment technique (and often full intervention protocol) aimed at modifying anxious cognitions by teaching youth to identify when they make threat attributions, consider alternate non-threatening attributions, and thereby change their anxious thought processes, resultant avoidance, and anxiety symptoms.
干预措施: Cognitive Restructuring (CR) (Other)
结局指标
主要结局
Change in Linguistic Interpretation Bias as Assessed by the Word-sentence Association Paradigm for Youth (WSAP-Y)
时间窗: 6 weeks following randomization/start of treatment (post-treatment study visit at Week 6)
The WSAP-Y is a computerized assessment of interpretation bias in which youth indicate whether word-sentence pairings are related. This measure provides information about the degree to which youth evidence interpretation bias, as well as a behavioral (reaction time) index for bias endorsement. For the primary outcome of percent threat interpretations endorsed, the possible range is 0 (zero) to 100%. Higher percentage indicates more threat interpretation bias (i.e., the youth endorsed a higher proportion of threat words as related to ambiguous sentences); lower scores indicate lower threat interpretation bias. Greater decrease in the percent of threat interpretations endorsed and lower absolute scores indicate "better" outcome (i.e., more reduction in threat interpretation bias; less interpretation bias overall).
Change in Visual Interpretation Bias as Assessed by the Ambiguous Faces Task
时间窗: 6 weeks following randomization/start of treatment (post-treatment study visit at Week 6)
Youth view faces portraying neutral expressions or subtle emotional expressions (i.e., morphed faces ranging in intensity of emotional valence). Youth categorization of faces as neutral or threatening provides their sensitivity and bias for reporting presence of threat. The criterion mean value in outcomes below reflects a score from -1 to 1, with higher negative numbers reflecting greater bias toward angry faces, and higher positive values approaching one reflecting a bias toward happy faces. Theoretically, higher positive values indicate "better" outcome such that youth have more positive bias toward facial stimuli.
Change in Self-reported Interpretation Bias as Measured by the Children's Automatic Thoughts Scale (CATS)
时间窗: 6 weeks following randomization/start of treatment (post-treatment study visit at Week 6)
The Children's Automatic Thoughts Scale is a youth self-report questionnaire which assesses presence and frequency of a variety of anxious thoughts from domains of: physical threat, social threat, personal failure, and anxious hostility. Total scores range from 0 to 160, with higher scores indicating more threat interpretation bias. Higher scores indicate "worse" outcome, or that youth self-report that they have more threatening thoughts and/or threatening thoughts at higher frequency; lower scores indicate "better" outcome or that youth self-report fewer threatening thoughts and/or threatening thoughts at lower frequency.
次要结局
- Number of CBM-I Trainings Completed of 16 Intended Sessions (CBM-I Arm Only)(6 weeks following randomization/start of treatment (post-treatment study visit at Week 6))
- Participant/Parent Acceptability Questionnaire (PAQ)(6 weeks following randomization/start of treatment (post-treatment study visit at Week 6))
- Anxiety symptom severity - PARS(6 weeks following randomization/start of treatment (post-treatment study visit at Week 6))
- Anxiety symptoms - SCARED(6 weeks following randomization/start of treatment (post-treatment study visit at Week 6))
研究者
Michelle Rozenman
Principal Investigator
University of Denver