Neural Mechanisms of Response Inhibition Training for OCRD

Официальное название

Neural Mechanisms of Response Inhibition Training for Obsessive-Compulsive Disorder and Related Conditions

Обзор

The impaired ability to suppress an inappropriate but pre-potent response (response inhibition; RI) characterizes several debilitating clinical problems, including obsessive-compulsive and related disorders (OCRD) such as obsessive-compulsive disorder, trichotillomania, and skin picking disorder. There is a critical need to develop an effective and durable treatment for OCRDs with demonstrable evidence for improving impaired RI. The purpose of our project is to examine the impact of a novel computerized intervention, response inhibition training (RIT), on neural indices of RI, and examine the mechanistic link between engagement of the neural RI targets and change in OCRD symptoms. To this end, this project will conduct a randomized clinical trial for individuals with OCD, trichotillomania, and/or skin picking disorders. Participants will be randomly assigned to 8 to 16 sessions of computerized RIT or a computerized placebo training. Various clinical, behavioral, and brain-imaging data will be acquired to evaluate the training effects at baseline, post-training, and 1-month follow-up periods.

Подробное описание

Research has documented abnormal inhibition-related brain activity as well as impaired behavioral performance of RI in OCRD. Despite the growing evidence suggesting a RI deficit as a fundamental process in OCRD, no validated treatment exists that can directly alter RI deficits and in turn ameliorate OCRD symptoms. It is vital to develop a highly specific intervention that precisely engages a theoretically and empirically well-grounded target such as RI deficits, to significantly improve the efficacy of our intervention efforts. The overarching goal of this study is to examine whether the computerized cognitive training program can improve the neural indicators of the ability to inhibit inappropriate responses, and produce a clinically meaningful level of reduction in obsessive-compulsive disorder and related symptoms. Our central hypothesis is that cognitive training designed to enhance RI will improve neural indices: fronto-basal ganglia circuitry, especially right inferior frontal cortex of RI among individuals with OCRDs. We also hypothesize that the change in the RI neural circuit will mediate the consequent clinical improvements in OCRD symptomatology.

Phase I (R61) will aim to examine change in neural RI indices via the RIT intervention, Adults diagnosed with OCRD problems (OCD, TTM, or SPD) will be randomly assigned to the RIT or placebo control (PLT) condition. At pre- and post-training, neurobehavioral measures of RI will be taken, including the Stop-Signal Task (SST) assessing SSRT and fMRI task assessing rIFC activation. Each RIT participant will continue with the training within the range of 8 to 16 sessions until the criterion-level change in SSRT is attained (based on the ongoing SSRT estimation), with the PLT group receiving comparable levels of training. We will also collect 1-month follow-up data on functional outcomes in order to obtain information on the effect of the intervention on the OCRD symptom indices.

Phase II (R33) is identical to Phase I in the overall study procedures. Adults diagnosed with OCRD problems will be assigned to RIT or PLT. Analytic focus will be on the reduction in OCRD symptoms and their potential mediational pathway (rather than the change in the neural RI indices, which is the primary analytic focus in Phase I). Other than these differences, the overall flow and procedures of the study will be identical between Phases I and II.

The key assessments will include the fMRI tasks of the RI processes and clinician-administered measures of OCRD symptoms. There are other self-reported, computerized, and clinician-administered measures that will be administered across various points over the course of the study.

Вмешательства

• Поведенческое Computerized cognitive training
  This intervention offers 45-minute computerized training sessions to each participant. This intervention aims to improve the individual's RI capabilities. All participants will receive 8 to 16 sessions after being randomized to this condition.
• Поведенческое Computerized placebo training
  This intervention offers 45-minute computerized placebo cognitive training sessions to each participant. This intervention aims to exert no focused training on RI capabilities. All participants will receive 8 to 16 sessions after being randomized to this condition.

Первичные конечные точки

• Change in obsessive-compulsive disorder symptom severity over time [Срок оценки: Week 0, Week 4, Week 8 ~ 12]
• Change in compulsive hair pulling symptom severity over time [Срок оценки: Week 0, Week 4, Week 8 ~ 12]
• Change in compulsive skin picking symptom severity over time [Срок оценки: Week 0, Week 4, Week 8 ~ 12]
• Change in activation in the right inferior frontal cortex (rIFC) [Срок оценки: Week 0, Week 4]

Вторичные конечные точки (1)

• Change in the Clinical Global Impression Scale [Срок оценки: Week 0, Week 4, Week 8 ~ 12]

Критерии участия

Критерии включения

• age between 18 and 60
• moderate level of OCRD symptoms (Yale-Brown Obsessive Compulsive Scale total ≥ 16, Massachusetts General Hospital-Hair pulling Scale total ≥ 12, or Skin Picking Scale-Revised total ≥ 7)
• a primary diagnosis of OCRD (i.e., OCD, TTM, or SPD)
• estimated IQ > 80
• presence of a RI deficits (SSRT ≥ 215ms).

Критерии исключения

• Current substance use disorder
• Severe ADHD
• Lifetime diagnosis of psychotic disorder, bipolar disorder, or schizophrenia
• Current psychotherapy
• Change in psychotropic medication status within 8 weeks before the study or during the study
• Use of stimulant medication
• Active suicidal risk
• Contraindications for MRI procedures

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• UWM Anxiety Disorders Laboratory — Milwaukee

Идентификаторы

NCT: NCT05377125 · PRO00042324

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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