Using rTMS to Explore Neural Mechanisms of Stress-Induced Opioid Use

NCT ID: NCT04181515

Last Updated: 2023-04-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-10
• Study Completion Date: 2023-04-10

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.

Conditions

Stress; Opioid-use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

placebo stressor, sham rTMS

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

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

placebo stressor

sham rTMS

Intervention Type: DEVICE

sham rTMS (inactive coil)

placebo stressor, active rTMS

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

Group Type: ACTIVE_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

placebo stressor

active rTMS

Intervention Type: DEVICE

active rTMS (10 Hz dlPFC stimulation in group 1; 1 Hz mPFC stimulation in group 2)

stressor, sham rTMS

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

Group Type: ACTIVE_COMPARATOR

Yohimbine + Hydrocortisone

Intervention Type: DRUG

Yohimbine 54mg + Hydrocortisone 20mg

sham rTMS

Intervention Type: DEVICE

sham rTMS (inactive coil)

stressor, active rTMS

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

Group Type: ACTIVE_COMPARATOR

Yohimbine + Hydrocortisone

Intervention Type: DRUG

Yohimbine 54mg + Hydrocortisone 20mg

active rTMS

Intervention Type: DEVICE

active rTMS (10 Hz dlPFC stimulation in group 1; 1 Hz mPFC stimulation in group 2)

Interventions

Placebo oral tablet

placebo stressor

Intervention Type: DRUG

Yohimbine + Hydrocortisone

Yohimbine 54mg + Hydrocortisone 20mg

Intervention Type: DRUG

sham rTMS

sham rTMS (inactive coil)

Intervention Type: DEVICE

active rTMS

active rTMS (10 Hz dlPFC stimulation in group 1; 1 Hz mPFC stimulation in group 2)

Intervention Type: DEVICE

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wayne State University

OTHER

Sponsor Role: lead

Responsible Party

Mark Greenwald, PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Greenwald, PhD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Other Identifiers

OTC-1

Identifier Type: -

Identifier Source: org_study_id