Effects of Pharmacological Stress and rTMS on Executive Function in Opioid Use Disorder

Официальное название

Effects of Pharmacological Stress and Repetitive Transcranial Magnetic Stimulation Interventions on Executive Function in Opioid Use Disorder

Обзор

This preliminary study is designed to evaluate mechanisms by which excitatory dorsolateral prefrontal cortex (dlPFC) repetitive transcranial magnetic stimulation (rTMS) (vs. sham) and pharmacological stress (vs. placebo) alter behavior in non-treatment seeking individuals with opioid use disorder (OUD). Specific Aims are to (1) Evaluate how stress impacts domains of behavior including (1a) executive function and (1b) opioid-seeking behavior; and (2) Determine whether rTMS stimulation attenuates (2a) executive dysfunction, (2b) stress-reactivity, and (2c) opioid-seeking in individuals with OUD not receiving treatment.

Подробное описание

This study will use a double-blind, 10Hz left dlPFC rTMS (vs. sham) and pharmacological stressor (\[yohimbine + hydrocortisone\] vs. placebo) within-subject, randomized crossover design. Each participant will complete 4 sessions (stressor vs. placebo, crossed with rTMS vs. sham), each separated by at least 1 week. Participants will complete these 4 (2x2 within subject) test conditions in randomized order: sham rTMS/placebo stress, sham rTMS/active stress, active rTMS/ placebo stress, and active rTMS/active stress.

The PI will perform randomization using a Latin Square and will assign participants to conditions and prepare medication (stressor or placebo) for each participant's sessions. The PI will keep others blinded and will not be involved in study assessments.

Вмешательства

• Препарат Yohimbine + Hydrocortisone
  Yohimbine (54mg bulk powder inside capsule) administered in combination with Hydrocortisone (20mg tablet inside capsule)
• Устройство Active rTMS
  10Hz rTMS over the left dlPFC
• Препарат Placebo
  lactose (inside capsule)
• Устройство Sham rTMS
  inactive stimulation over the left dlPFC

Первичные конечные точки

• Color-Word Stroop Task [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• Digit Span Task [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• Wisconsin Card Sorting Task [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• Emotion Regulation Task [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• Positive and Negative Affect Schedule [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• State-Trait Anxiety Inventory [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• Monetary Incentive Delay Task [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• Delay Discounting Task [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• Drug/Money Choice Task [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• Systolic blood pressure [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]

Вторичные конечные точки (3)

• Opioid craving [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• Opioid agonist symptoms [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]
• Opioid withdrawal symptoms [Срок оценки: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)]

Критерии участия

Критерии включения

• Meet DSM-5 criteria for OUD;
• Age 21-60 yr;
• Right handed;
• Males and non-pregnant/non-lactating females;
• cognitively intact (total IQ score >80 on Shipley Institute of Living Scale);
• Screening cardiovascular indices within ranges for safe use of the pharmacological stressor: resting HR 50-90 bpm, systolic BP 90-140 mmHg, and diastolic BP 50-90 mmHg;
• Use alcohol and/or marijuana <3 times/week; each "time" should consist of <1 marijuana "joint" equivalent and <3 alcoholic drinks.

Критерии исключения

• Under influence of any substance during session;
• Past 7-day use of illicit drugs other than opioids (except marijuana, which is legal in Michigan);
• Urinalysis positive for cocaine metabolites, benzodiazepines, barbiturates, amphetamines or pregnancy;
• Medical conditions prohibiting use of rTMS (e.g. seizure history; based on rTMS screening questionnaire);
• Lifetime diagnosis of: psychotic disorder, bipolar disorder, generalized anxiety disorder, or obsessive compulsive disorder; major depression in the past 5 years; or potentially antisocial personality disorder (if the clinical psychologist judges such behaviors to be potentially disruptive or unsafe in our lab);
• Past-year SUD other than OUD;
• Acute/unstable illness: conditions making it unsafe for participation (e.g. neurological, cardiovascular, pulmonary, or systemic diseases);
• Lactose intolerance (placebo dose);
• Any prohibited medications: medications that lower seizure threshold, psychiatric medications, prescription pain medications, or blood pressure medications;
• Chronic head or neck pain; and
• Past-month participation in a research study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Tolan Park Medical Building — Detroit

Идентификаторы

NCT: NCT04231708 · DL-STR-OUD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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