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

Stress Clinical Trial

— OTC-1  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04181515
• Other study ID #: OTC-1
• Status: Withdrawn
• Phase: Phase 2
• Start date: April 10, 2023
• Est. completion date: April 10, 2023

Study information

• Verified date: April 2023
• Source: Wayne State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 10, 2023
• Est. primary completion date: April 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Opioid-Related Disorders
• Opioid-use Disorder
• Stress

Intervention

Drug:
• Placebo oral tablet
placebo stressor
• Yohimbine + Hydrocortisone
Yohimbine 54mg + Hydrocortisone 20mg

Device:
• sham rTMS
sham rTMS (inactive coil)
• active rTMS
active rTMS (10 Hz dlPFC stimulation in group 1; 1 Hz mPFC stimulation in group 2)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wayne State University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Heart rate	Heart rate (beats/min)	change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)