Using Repetitive Transcranial Magnetic Stimulation (rTMS) to Explore Neural Mechanisms of Stress-Induced Opioid Use
| Registry | NCT04181515, acronym OTC-1 |
|---|---|
| Status | Withdrawn - Lack of funding |
| Phase | Phase 2 |
| Study type | Interventional; randomized, crossover, masking: triple, basic science |
| Sponsor | Wayne State University (Other) |
| Conditions | Stress, Opioid-use Disorder |
| Interventions | Placebo oral tablet, Yohimbine + Hydrocortisone, sham rTMS, active rTMS (Drug, device) |
| Dates | start 2023-04-10, primary completion 2023-04-10, completion 2023-04-10, first posted 2019-11-29, last updated 2023-04-13 |
Related Papers Related Patents Related Grants Related Experts
All trials for Stress All trials for Opioid-use Disorder All trials of Placebo oral tablet All trials of Yohimbine + Hydrocortisone
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.
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| placebo stressor, sham rTMS | Placebo comparator | Drug: Placebo oral tablet; Device: sham rTMS | placebo stressor (lactose), sham rTMS (inactive coil) |
| placebo stressor, active rTMS | Active comparator | Drug: Placebo oral tablet; Device: active rTMS | placebo stressor (lactose), active rTMS (10 Hz dlPFC in group 1; 1 Hz mPFC in group 2) |
| stressor, sham rTMS | Active comparator | Drug: Yohimbine + Hydrocortisone; Device: sham rTMS | stressor (yohimbine 54mg + hydrocortisone 20mg), sham rTMS (inactive coil) |
| stressor, active rTMS | Active comparator | Drug: Yohimbine + Hydrocortisone; Device: active rTMS | stressor (yohimbine 54mg + hydrocortisone 20mg), active rTMS (10 Hz dlPFC in group 1; 1 Hz mPFC in group 2) |
Sex: All, ages: 21 Years to 60 Years
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