Clinical trial NCT04231708: Effects of Pharmacological Stress and rTMS on Executive Function in Opioid Use Disorder
Official title: Effects of Pharmacological Stress and Repetitive Transcranial Magnetic Stimulation Interventions on Executive Function in Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Opioid Use Disorder
Lead sponsor: Wayne State University
Sponsor class: OTHER
First posted: 2020-01-18
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, 10Hz left dlPFC rTMS (vs. sham) X pharmacological stressor (vs. placebo) within-subject, randomized crossover design.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Color-Word Stroop Task
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Digit Span Task
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Wisconsin Card Sorting Task
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Emotion Regulation Task
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Positive and Negative Affect Schedule
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: State-Trait Anxiety Inventory
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Monetary Incentive Delay Task
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Delay Discounting Task
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Drug/Money Choice Task
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Systolic blood pressure
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Diastolic blood pressure
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Heart rate
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Saliva cortisol level
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Saliva alpha-amylase level
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Serum prolactin level
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Serum brain derived neurotrophic factor (BDNF) level
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Relative electroencephalogram (EEG) gamma power
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Secondary outcomes:
measure: Opioid craving
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Opioid agonist symptoms
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Opioid withdrawal symptoms
timeFrame: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Tolan Park Medical Building
state: Michigan
Study officials:
References: