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

Opioid Use Disorder Clinical Trial

Official title:

Effects of Pharmacological Stress and Repetitive Transcranial Magnetic Stimulation Interventions on Executive Function in Opioid Use Disorder

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04231708
• Other study ID #: DL-STR-OUD
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 2024
• Est. completion date: December 2026

Study information

• Verified date: March 2024
• Source: Wayne State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This study will use a double-blind, 10Hz left dlPFC rTMS (vs. sham) and pharmacological stressor ([yohimbine + hydrocortisone] vs. placebo) within-subject, randomized crossover design. Each participant will complete 4 sessions (stressor vs. placebo, crossed with rTMS vs. sham), each separated by at least 1 week. Participants will complete these 4 (2x2 within subject) test conditions in randomized order: sham rTMS/placebo stress, sham rTMS/active stress, active rTMS/ placebo stress, and active rTMS/active stress.

The PI will perform randomization using a Latin Square and will assign participants to conditions and prepare medication (stressor or placebo) for each participant's sessions. The PI will keep others blinded and will not be involved in study assessments.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 2026
• Est. primary completion date: October 2026
• 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; and

• Past-month participation in a research study.

Related Conditions & MeSH terms

• Opioid Use Disorder
• Opioid-Related Disorders
• Substance-Related Disorders

Intervention

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

Device:
• Active rTMS
10Hz rTMS over the left dlPFC

Drug:
• Placebo
lactose (inside capsule)

Device:
• Sham rTMS
inactive stimulation over the left dlPFC

Locations

Country	Name	City	State
United States	Tolan Park Medical Building	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Wayne State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Systolic blood pressure	millimeters mercury (mmHg)	change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Primary	Diastolic blood pressure	millimeters mercury (mmHg)	change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Primary	Heart rate	beats per minute	change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Opioid craving	Desire for Drug Questionnaire total score; higher scores indicate greater craving	change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Secondary	Opioid agonist symptoms	Opiate-32 questionnaire agonist symptom total score; higher scores indicate greater opioid symptom severity	change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Secondary	Opioid withdrawal symptoms	Opiate-32 questionnaire withdrawal symptom total score; higher scores indicate greater withdrawal severity	change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)