Cognitive and neural mechanisms of cognitive-behavioral therapy for avoidant/restrictive food intake disorder

回避/限制性食物摄入障碍的认知行为疗法的认知和神经机制

基本信息

批准号：
10570372
负责人：
Kamryn T Eddy
金额：
$ 108.3万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-07 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10570372
关键词：
Adolescent Adult Advocate Affect Aftercare Age Amygdaloid structure Anterior Brain region Central Nervous System Child Chronic Clinical Clinical Trials Cognitive Cognitive Therapy Counseling Cues Data Dependence Development Disease remission Dose Eating Eating Disorders Evidence based treatment Exhibits Food Fright Functional Magnetic Resonance Imaging Hyperactivity Impairment Individual Intervention Interview Investigational Therapies Learning Malnutrition Manuals Measures Mediating Medical Motivation National Institute of Mental Health Occupational Therapy Outcome Patients Persons Phase Pica Disease Prevention Randomized Randomized, Controlled Trials Recommendation Risk Rumination Disorders Standardization Statistical Data Interpretation Testing Therapeutic Intervention Thinking Validation Work Youth active control arm avoidant restrictive food intake disorder behavior change cingulate cortex clinical trial analysis dietary supplements effectiveness trial efficacy trial food avoidance multidisciplinary neuromechanism novel nutrition pressure prevent psychologic psychosocial response severe mental illness telehealth treatment of anxiety disorders trend

项目摘要

ABSTRACT Avoidant/restrictive food intake disorder (ARFID) affects 3% of children and adolescents and results in nutritional deficiencies, supplement dependence, and psychosocial impairment. ARFID follows a chronic course, and has no evidence-based treatment. The hallmark feature of ARFID is food avoidance, which may be maintained by extreme levels of food neophobia and/or hyperactivation of fear circuitry in response to food cues. Our team has developed a manualized cognitive-behavioral therapy (CBT-AR) that directly targets both food neophobia (cognitive mechanism) and fear circuitry (neural mechanism) to reduce food avoidance (clinical outcome). In line with NIMH’s experimental therapeutics approach, in this exploratory/developmental phased R61/R33, we will leverage a multidisciplinary team of experts in the treatment of ARFID, neural mechanisms of food motivation, and statistical analysis of clinical trials to conduct a mechanistic randomized controlled trial of CBT-AR. First, to establish target engagement, we will randomize 50 youth (ages 10-18yo) with ARFID in a 1:1 ratio to 15 weekly sessions (via telehealth) of CBT-AR vs. nutrition counseling to establish target engagement. We chose nutrition counseling as our active control because it does not include the crucial CBT-AR intervention of exposure, and is therefore unlikely to engage our target mechanisms. We hypothesize that, compared to nutrition counseling, patients randomized to CBT-AR will show significantly greater decreases in food neophobia (cognitive mechanism) and fear circuitry (neural mechanism) in response to food cues during a standardized fMRI food cue paradigm (primary ROI: anterior cingulate cortex [ACC]; secondary ROIs: amygdala, orbitofrontal cortex [OFC]). We will also examine weekly change in food neophobia (cognitive mechanism) to identify the number of sessions at which further benefit ceases, and use this optimized dose of CBT-AR for the R33. We will move on to the R33 if we are able to demonstrate a reduction of at least d=.40 in the CBT-AR group from pre- to post-treatment AND a post-treatment between- group difference of at least d=.40 in CBT-AR vs. nutrition counseling in either food neophobia (cognitive mechanism) OR fear circuitry (Go/No-Go ROI: ACC; neural mechanism). Next, we will randomize 70 youth (ages 10-18yo) with ARFID in a 1:1 fashion to the optimized dose of CBT-AR or the same number of sessions of nutrition counseling to replicate target engagement and establish target validation. We hypothesize that, compared to nutrition counseling, patients randomized to CBT-AR will exhibit significantly greater reductions in food avoidance, and that these reductions in food avoidance will be mediated by reductions in food neophobia (cognitive mechanism) and fear circuitry (neural mechanism) activation. If successful, the proposed intervention (CBT-AR) could fill an important unmet need for those living with ARFID and pave the way for larger-scale efficacy and effectiveness trials.

抽象的回避/限制性食物摄入障碍 (ARFID) 影响 3% 的儿童和青少年及其结果营养缺乏、补充剂依赖和社会心理障碍都伴随着慢性病。当然，并且没有基于证据的治疗方法，ARFID 的标志性特征是避免食物，这可能是。通过极端水平的食物新恐惧症和/或恐惧电路的过度激活来应对我们的团队开发了一种直接针对食物线索的手动认知行为疗法（CBT-AR）。食物恐惧症（认知机制）和恐惧回路（神经机制）都可以减少食物回避（临床结果）与 NIMH 的实验治疗方法一致，在这个探索性/发展中。分阶段 R61/R33，我们将利用多学科专家团队来治疗 ARFID、神经食物动机的机制，以及临床试验的统计分析，以进行机制随机 CBT-AR 的对照试验首先，为了确定目标参与度，我们将随机抽取 50 名青少年（10-18 岁）。以 1:1 的比例使用 ARFID 进行每周 15 次 CBT-AR 会议（通过远程医疗）与营养咨询，以建立我们选择营养咨询作为我们的主动控制，因为它不包括暴露的关键 CBT-AR 干预，因此不太可能参与我们的目标机制。其次，与营养咨询相比，随机接受 CBT-AR 的患者将表现出显着的食物恐惧症（认知机制）和恐惧回路（神经机制）显着减少在标准化功能磁共振成像食物线索范式中对食物线索的反应（主要投资回报率：前扣带皮层 [ACC]；次要 ROI：杏仁核、眶额皮质 [OFC]）我们还将检查每周的食物变化。 Neophobia（认知机制）来确定进一步获益停止的会话次数，并使用如果我们能够证明 R33 的 CBT-AR 优化剂量，我们将继续研究 R33。 CBT-AR 组从治疗前到治疗后至少减少 d=.40，并且治疗后- CBT-AR 与营养咨询在任一食物新恐惧症（认知机制）或恐惧电路（Go/No-Go ROI：ACC；神经机制）接下来，我们将随机分配 70 名青少年。（10-18 岁）以 1:1 的方式使用 ARFID 与 CBT-AR 的优化剂量或相同次数的疗程营养咨询，以复制目标参与并建立目标验证。与营养咨询相比，随机接受 CBT-AR 的患者将表现出显着更大的减少避免食物的减少，并且这些避免食物的减少将通过减少食物来调节如果成功，恐惧症（认知机制）和恐惧电路（神经机制）激活。拟议的干预措施（CBT-AR）可以满足 ARFID 生活者未满足的重要需求，并为进行更大规模功效和有效性试验的方法。