Using rTMS to Explore Neural Mechanisms of Stress-Induced Opioid Use (OTC-1)

Wayne State University

Status and phase: Withdrawn; Phase 2

Conditions: Opioid-use Disorder; Stress

Treatments: Device: sham rTMS; Drug: Yohimbine + Hydrocortisone; Drug: Placebo oral tablet; Device: active rTMS

Study type: Interventional

Funder types: Other

Identifiers

NCT04181515

OTC-1

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 21 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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0 participants in 4 patient groups, including a placebo group

placebo stressor, sham rTMS

Placebo Comparator group

Description:

placebo stressor (lactose), sham rTMS (inactive coil)

Treatment:

Drug: Placebo oral tablet

Device: sham rTMS

placebo stressor, active rTMS

Active Comparator group

Description:

placebo stressor (lactose), active rTMS (10 Hz dlPFC in group 1; 1 Hz mPFC in group 2)

Treatment:

Drug: Placebo oral tablet

Device: active rTMS

stressor, sham rTMS

Active Comparator group

Description:

stressor (yohimbine 54mg + hydrocortisone 20mg), sham rTMS (inactive coil)

Treatment:

Drug: Yohimbine + Hydrocortisone

Device: sham rTMS

stressor, active rTMS

Active Comparator group

Description:

stressor (yohimbine 54mg + hydrocortisone 20mg), active rTMS (10 Hz dlPFC in group 1; 1 Hz mPFC in group 2)

Treatment:

Drug: Yohimbine + Hydrocortisone

Device: active rTMS