Effects of Pharmacological Stress and rTMS on Executive Function in Opioid Use Disorder

NCT04231708 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: DL-STR-OUD
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This preliminary study is designed to evaluate mechanisms by which excitatory dorsolateral prefrontal cortex (dlPFC) repetitive transcranial magnetic stimulation (rTMS) (vs. sham) and pharmacological stress (vs. placebo) alter behavior in non-treatment seeking individuals with opioid use disorder (OUD). Specific Aims are to (1) Evaluate how stress impacts domains of behavior including (1a) executive function and (1b) opioid-seeking behavior; and (2) Determine whether rTMS stimulation attenuates (2a) executive dysfunction, (2b) stress-reactivity, and (2c) opioid-seeking in individuals with OUD not receiving treatment.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (17)

• Color-Word Stroop Task

  measures cognitive control in response to opioid-related words.

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Digit Span Task

  measures verbal working memory. Participants are asked to repeat strings of numbers of increasing length, both forward and backward.

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Wisconsin Card Sorting Task

  measures ability to shift set and assesses cognitive flexibility.

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Emotion Regulation Task

  subjects rate the unpleasantness and arousal of different emotional pictures

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Positive and Negative Affect Schedule

  subjects rate their positive and negative affect

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• State-Trait Anxiety Inventory

  subjects rate their level state anxiety

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Monetary Incentive Delay Task

  Participants respond to a visual target that follows 2 different cues: incentive or non-incentive. No reward or punishment occurs on non-incentive trials. On incentive trials, participants must respond within a fixed amount of time. In the reward condition, responses within that time result in receiving the incentive , else nothing. In the punishment condition, the participant will lose money if they do not respond within the time limit

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Delay Discounting Task

  Participants perform a brief (\<1min) hypothetical version of the traditional monetary task with a 5-trial adjusting delay previously validated to rapidly assess discount rate

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Drug/Money Choice Task

  participants choose hypothetically between a constant amount of their preferred opioid ($10 unit dose) or money ($2)

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Systolic blood pressure

  millimeters mercury (mmHg)

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Diastolic blood pressure

  millimeters mercury (mmHg)

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Heart rate

  beats per minute

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Saliva cortisol level

  measure of the activity of the HPA axis

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Saliva alpha-amylase level

  indirect measure of adrenergic stimulation

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Serum prolactin level

  indirect measure of dopamine stimulation

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Serum brain derived neurotrophic factor (BDNF) level

  indirect measure of brain derived neurotrophic factor activation

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Relative electroencephalogram (EEG) gamma power

  Prefrontal gamma (25-100 Hz) EEG power, relative to slow-wave EEG power, is a stress biomarker

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

Secondary Outcomes (3)

• Opioid craving

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Opioid agonist symptoms

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

• Opioid withdrawal symptoms

  change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)

Study Arms (4)

placebo stressor, sham rTMS

PLACEBO COMPARATOR

Placebo stressor (lactose) + sham (inactive) rTMS over the left dlPFC

Drug: Placebo; Device: Sham rTMS

placebo stressor, active rTMS

EXPERIMENTAL

Placebo stressor (lactose) + active 10Hz rTMS over the left dlPFC

Device: Active rTMS; Drug: Placebo

active stressor, sham rTMS

EXPERIMENTAL

Stressor (yohimbine 54mg + hydrocortisone 20mg) + sham (inactive) rTMS over the left dlPFC

Drug: Yohimbine + Hydrocortisone; Device: Sham rTMS

active stressor, active rTMS

EXPERIMENTAL

Stressor (yohimbine 54mg + hydrocortisone 20mg) + active 10Hz rTMS over the left dlPFC

Drug: Yohimbine + Hydrocortisone; Device: Active rTMS

Interventions

Yohimbine + Hydrocortisone DRUG

Yohimbine (54mg bulk powder inside capsule) administered in combination with Hydrocortisone (20mg tablet inside capsule)

active stressor, active rTMS; active stressor, sham rTMS

Active rTMS DEVICE

10Hz rTMS over the left dlPFC

active stressor, active rTMS; placebo stressor, active rTMS

Placebo DRUG

lactose (inside capsule)

placebo stressor, active rTMS; placebo stressor, sham rTMS

Sham rTMS DEVICE

inactive stimulation over the left dlPFC

active stressor, sham rTMS; placebo stressor, sham rTMS

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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; and
• Past-month participation in a research study.

Sponsors & Collaborators

• Wayne State University: lead

Study Sites (1)

Tolan Park Medical Building

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Yohimbine; Hydrocortisone

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Placebo (lactose) for pharmacological stressor, and sham for dlPFC rTMS
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Double-blind, 10Hz left dlPFC rTMS (vs. sham) X pharmacological stressor (vs. placebo) within-subject, randomized crossover design.

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: January 18, 2020
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)