Clinical trial NCT04181515: Using rTMS to Explore Neural Mechanisms of Stress-Induced Opioid Use
Official title: Using Repetitive Transcranial Magnetic Stimulation (rTMS) to Explore Neural Mechanisms of Stress-Induced Opioid Use
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Stress
Opioid-use Disorder
Lead sponsor: Wayne State University
Sponsor class: OTHER
First posted: 2019-11-29
Enrollment: 0
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: mixed design, with 4 (2x2) within-subject conditions (placebo vs. stressor X sham vs. rTMS), each occurring in two parallel groups (10 Hz dorsolateral prefrontal cortex vs. sham rTMS in group 1, and 1 Hz medial prefrontal cortex vs. sham rTMS in group 2)
Primary purpose: BASIC_SCIENCE

Brief summary: This study will use a stress (vs. placebo) exposure model, paired with single-session sham vs. active rTMS at two distinct cortical locations (dlPFC vs. mPFC in parallel groups) to assess whether rTMS neuromodulation at these alternative loci differentially influence stress-reactivity and opioid reinforcement in non-treatment seeking participants with OUD. Stress-reactivity will be measured using cognitive, affective, behavioral and biological phenotypes.

Detailed description: The Competing Neurobehavioral Decisions Systems (CNDS) model of addiction suggests that persons with SUDs have hyperactive limbic reward circuitry and hypoactive executive control circuitry. CNDS theory supports targeting the dorsolateral prefrontal cortex (dlPFC, part of executive control circuit) and other cortical targets with repetitive transcranial magnetic stimulation (rTMS). One candidate-the medial prefrontal cortex (mPFC)-is part of limbic reward circuitry and accessible using rTMS. We validated a rigorous pharmacological stress-induction method (yohimbine + hydrocortisone) that emulates endogenous stress-reactivity and have established linkages between stress-exposure, executive dysfunction, and drug seeking. Our lab is developing rTMS as a potential "anti-stress" neuromodulation approach in people with opioid use disorder (OUD).

This study will use a stress (vs. placebo) exposure model, paired with single-session sham vs. active rTMS at two distinct cortical locations (dlPFC vs. mPFC in parallel groups) to assess whether rTMS neuromodulation at these alternative cortical loci differentially influence stress-reactivity and opioid reinforcement in non-treatment seeking participants with OUD. Stress-reactivity will be measured using cognitive, affective, behavioral and biological phenotypes.

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
* Past-month participation in a research study

Primary outcomes:
measure: Addiction Stroop task
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Digit Span Task
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Wisconsin Card Sorting Task
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Monetary Incentive Delay task
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Delay Discounting task
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Drug/Money Choice Task
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Blood pressure
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Heart rate
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Saliva cortisol level
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Saliva alpha-amylase level
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Serum prolactin level
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Serum BDNF level
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Positive and Negative Affect Schedule (PANAS) positive affect
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Positive and Negative Affect Schedule (PANAS) negative affect
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: State Trait Anxiety Inventory
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Desire for Drug Questionnaire
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Opiate-32 Questionnaire, Agonist score
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Opiate-32 Questionnaire, Withdrawal score
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure: Resting-state EEG activation
timeFrame: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Wayne State University
name: Mark Greenwald, PhD
role: PRINCIPAL_INVESTIGATOR
References: