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

NCT04181515 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: OTC-1
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Stress; Opioid-use Disorder

Outcome Measures

Primary Outcomes (19)

• Addiction Stroop task

  reaction time (msec) measure of cognitive interference

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

• Digit Span Task

  number of digits recalled, measure of verbal working memory

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

• Wisconsin Card Sorting Task

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

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

• Monetary Incentive Delay task

  number of rewards received, measure of motivation

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

• Delay Discounting task

  rate of monetary discounting

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

• Drug/Money Choice Task

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

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

• Blood pressure

  Systolic/diastolic BP (mm Hg)

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

• Heart rate

  Heart rate (beats/min)

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

• Saliva cortisol level

  Saliva cortisol level (µg/dL)

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

• Saliva alpha-amylase level

  Saliva alpha-amylase level (U/mL)

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

• Serum prolactin level

  Serum prolactin level (pg/dL)

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

• Serum BDNF level

  Serum brain derived neurotrophic factor level (pg/dL)

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

• Positive and Negative Affect Schedule (PANAS) positive affect

  10-item sub scale score of positive affect

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

• Positive and Negative Affect Schedule (PANAS) negative affect

  10-item sub scale score of negative affect

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

• State Trait Anxiety Inventory

  state anxiety scores

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

• Desire for Drug Questionnaire

  opioid craving score

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

• Opiate-32 Questionnaire, Agonist score

  total opioid agonist score (16 items)

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

• Opiate-32 Questionnaire, Withdrawal score

  total opioid withdrawal symptom score (16 items)

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

• Resting-state EEG activation

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

  change from pre- and 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 rTMS (inactive coil)

Drug: Placebo oral tablet; Device: sham rTMS

placebo stressor, active rTMS

ACTIVE COMPARATOR

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

Drug: Placebo oral tablet; Device: active rTMS

stressor, sham rTMS

ACTIVE COMPARATOR

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

Drug: Yohimbine + Hydrocortisone; Device: sham rTMS

stressor, active rTMS

ACTIVE COMPARATOR

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

Drug: Yohimbine + Hydrocortisone; Device: active rTMS

Interventions

Placebo oral tablet DRUG

placebo stressor

placebo stressor, active rTMS; placebo stressor, sham rTMS

Yohimbine + Hydrocortisone DRUG

Yohimbine 54mg + Hydrocortisone 20mg

stressor, active rTMS; stressor, sham rTMS

sham rTMS DEVICE

sham rTMS (inactive coil)

placebo stressor, sham rTMS; stressor, sham rTMS

active rTMS DEVICE

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

placebo stressor, active rTMS; stressor, active 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
• Past-month participation in a research study

Sponsors & Collaborators

• Wayne State University: lead

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 Officials

• Mark Greenwald, PhD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: placebo for stressor, and sham figure of 8 coil for rTMS
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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)

Study Record Dates

• First Submitted: November 24, 2019
• First Posted: November 29, 2019
• Study Start: April 10, 2023
• Primary Completion: April 10, 2023
• Study Completion: April 10, 2023
• Last Updated: April 13, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Available after the study is completed
• Access Criteria: Qualified investigators may apply in writing.