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

Primary Purpose

Stress, Opioid-use Disorder

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Placebo oral tablet

Yohimbine + Hydrocortisone

sham rTMS

active rTMS

About this trial

This is an interventional basic science trial for Stress

Eligibility Criteria

21 Years - 60 Years (Adult)All SexesDoes not accept 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Arm Label

placebo stressor, sham rTMS

placebo stressor, active rTMS

stressor, sham rTMS

stressor, active rTMS

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

Addiction Stroop task

reaction time (msec) measure of cognitive interference

Digit Span Task

number of digits recalled, measure of verbal working memory

Wisconsin Card Sorting Task

number of correct items, measures ability to shift set and assesses cognitive flexibility

Monetary Incentive Delay task

number of rewards received, measure of motivation

Delay Discounting task

rate of monetary discounting

Drug/Money Choice Task

number of hypothetical choices between a constant amount of preferred opioid (relative to money)

Blood pressure

Systolic/diastolic BP (mm Hg)

Heart rate

Heart rate (beats/min)

Saliva cortisol level

Saliva cortisol level (µg/dL)

Saliva alpha-amylase level

Saliva alpha-amylase level (U/mL)

Serum prolactin level

Serum prolactin level (pg/dL)

Serum BDNF level

Serum brain derived neurotrophic factor level (pg/dL)

Positive and Negative Affect Schedule (PANAS) positive affect

10-item sub scale score of positive affect

Positive and Negative Affect Schedule (PANAS) negative affect

10-item sub scale score of negative affect

State Trait Anxiety Inventory

state anxiety scores

Desire for Drug Questionnaire

opioid craving score

Opiate-32 Questionnaire, Agonist score

total opioid agonist score (16 items)

Opiate-32 Questionnaire, Withdrawal score

total opioid withdrawal symptom score (16 items)

Resting-state EEG activation

relative (gamma band ÷ slow band) ratio in electroencephalogram (EEG) power during resting state

Secondary Outcome Measures

Full Information

NCT ID

NCT04181515

First Posted

November 24, 2019

Last Updated

April 10, 2023

Sponsor

Wayne State University

1. Study Identification

Unique Protocol Identification Number

NCT04181515

Brief Title

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

Acronym

OTC-1

Official Title

Using Repetitive Transcranial Magnetic Stimulation (rTMS) to Explore Neural Mechanisms of Stress-Induced Opioid Use

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Lack of funding

Study Start Date

April 10, 2023 (Actual)

Primary Completion Date

April 10, 2023 (Actual)

Study Completion Date

April 10, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Wayne State University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stress, Opioid-use Disorder

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

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)

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

placebo for stressor, and sham figure of 8 coil for rTMS

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

placebo stressor, sham rTMS

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

placebo stressor, active rTMS

Arm Type

Active Comparator

Arm Description

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

Arm Title

stressor, sham rTMS

Arm Type

Active Comparator

Arm Description

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

Arm Title

stressor, active rTMS

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo oral tablet

Intervention Description

placebo stressor

Intervention Type

Drug

Intervention Name(s)

Yohimbine + Hydrocortisone

Intervention Description

Yohimbine 54mg + Hydrocortisone 20mg

Intervention Type

Device

Intervention Name(s)

sham rTMS

Intervention Description

sham rTMS (inactive coil)

Intervention Type

Device

Intervention Name(s)

active rTMS

Intervention Description

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

Primary Outcome Measure Information:

Title

Addiction Stroop task

Description

reaction time (msec) measure of cognitive interference

Time Frame