Back to resultsEffects of Pharmacological Stress and rTMS on Executive Function in Opioid Use Disorder
Primary Purpose
Opioid Use Disorder
Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Yohimbine + Hydrocortisone
Active rTMS
Placebo
Sham rTMS
Sponsored by
About this trial
This is an interventional basic science trial for Opioid Use Disorder
Eligibility Criteria
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.
Sites / Locations
- Tolan Park Medical Building
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
placebo stressor, sham rTMS
placebo stressor, active rTMS
active stressor, sham rTMS
active stressor, active rTMS
Arm Description
Placebo stressor (lactose) + sham (inactive) rTMS over the left dlPFC
Placebo stressor (lactose) + active 10Hz rTMS over the left dlPFC
Stressor (yohimbine 54mg + hydrocortisone 20mg) + sham (inactive) rTMS over the left dlPFC
Stressor (yohimbine 54mg + hydrocortisone 20mg) + active 10Hz rTMS over the left dlPFC
Outcomes
Primary Outcome Measures
Color-Word Stroop Task
measures cognitive control in response to opioid-related words.
Digit Span Task
measures verbal working memory. Participants are asked to repeat strings of numbers of increasing length, both forward and backward.
Wisconsin Card Sorting Task
measures ability to shift set and assesses cognitive flexibility.
Emotion Regulation Task
subjects rate the unpleasantness and arousal of different emotional pictures
Positive and Negative Affect Schedule
subjects rate their positive and negative affect
State-Trait Anxiety Inventory
subjects rate their level state anxiety
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
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
Drug/Money Choice Task
participants choose hypothetically between a constant amount of their preferred opioid ($10 unit dose) or money ($2)
Systolic blood pressure
millimeters mercury (mmHg)
Diastolic blood pressure
millimeters mercury (mmHg)
Heart rate
beats per minute
Saliva cortisol level
measure of the activity of the HPA axis
Saliva alpha-amylase level
indirect measure of adrenergic stimulation
Serum prolactin level
indirect measure of dopamine stimulation
Serum brain derived neurotrophic factor (BDNF) level
indirect measure of brain derived neurotrophic factor activation
Relative electroencephalogram (EEG) gamma power
Prefrontal gamma (25-100 Hz) EEG power, relative to slow-wave EEG power, is a stress biomarker
Secondary Outcome Measures
Opioid craving
Desire for Drug Questionnaire total score; higher scores indicate greater craving
Opioid agonist symptoms
Opiate-32 questionnaire agonist symptom total score; higher scores indicate greater opioid symptom severity
Opioid withdrawal symptoms
Opiate-32 questionnaire withdrawal symptom total score; higher scores indicate greater withdrawal severity
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04231708
Brief Title
Effects of Pharmacological Stress and rTMS on Executive Function in Opioid Use Disorder
Official Title
Effects of Pharmacological Stress and Repetitive Transcranial Magnetic Stimulation Interventions on Executive Function in Opioid Use Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
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
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Use Disorder
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Double-blind, 10Hz left dlPFC rTMS (vs. sham) X pharmacological stressor (vs. placebo) within-subject, randomized crossover design.
Masking
ParticipantOutcomes Assessor
Masking Description
Placebo (lactose) for pharmacological stressor, and sham for dlPFC rTMS
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
placebo stressor, sham rTMS
Arm Type
Placebo Comparator
Arm Description
Placebo stressor (lactose) + sham (inactive) rTMS over the left dlPFC
Arm Title
placebo stressor, active rTMS
Arm Type
Experimental
Arm Description
Placebo stressor (lactose) + active 10Hz rTMS over the left dlPFC
Arm Title
active stressor, sham rTMS
Arm Type
Experimental
Arm Description
Stressor (yohimbine 54mg + hydrocortisone 20mg) + sham (inactive) rTMS over the left dlPFC
Arm Title
active stressor, active rTMS
Arm Type
Experimental
Arm Description
Stressor (yohimbine 54mg + hydrocortisone 20mg) + active 10Hz rTMS over the left dlPFC
Intervention Type
Drug
Intervention Name(s)
Yohimbine + Hydrocortisone
Intervention Description
Yohimbine (54mg bulk powder inside capsule) administered in combination with Hydrocortisone (20mg tablet inside capsule)
Intervention Type
Device
Intervention Name(s)
Active rTMS
Intervention Description
10Hz rTMS over the left dlPFC
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
lactose (inside capsule)
Intervention Type
Device
Intervention Name(s)
Sham rTMS
Intervention Description
inactive stimulation over the left dlPFC
Primary Outcome Measure Information:
Title
Color-Word Stroop Task
Description
measures cognitive control in response to opioid-related words.
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Digit Span Task
Description
measures verbal working memory. Participants are asked to repeat strings of numbers of increasing length, both forward and backward.
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Wisconsin Card Sorting Task
Description
measures ability to shift set and assesses cognitive flexibility.
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Emotion Regulation Task
Description
subjects rate the unpleasantness and arousal of different emotional pictures
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Positive and Negative Affect Schedule
Description
subjects rate their positive and negative affect
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
State-Trait Anxiety Inventory
Description
subjects rate their level state anxiety
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Monetary Incentive Delay Task
Description
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
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Delay Discounting Task
Description
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
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Drug/Money Choice Task
Description
participants choose hypothetically between a constant amount of their preferred opioid ($10 unit dose) or money ($2)
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Systolic blood pressure
Description
millimeters mercury (mmHg)
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Diastolic blood pressure
Description
millimeters mercury (mmHg)
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Heart rate
Description
beats per minute
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Saliva cortisol level
Description
measure of the activity of the HPA axis
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Saliva alpha-amylase level
Description
indirect measure of adrenergic stimulation
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Serum prolactin level
Description
indirect measure of dopamine stimulation
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Serum brain derived neurotrophic factor (BDNF) level
Description
indirect measure of brain derived neurotrophic factor activation
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Relative electroencephalogram (EEG) gamma power
Description
Prefrontal gamma (25-100 Hz) EEG power, relative to slow-wave EEG power, is a stress biomarker
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Secondary Outcome Measure Information:
Title
Opioid craving
Description
Desire for Drug Questionnaire total score; higher scores indicate greater craving
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Opioid agonist symptoms
Description
Opiate-32 questionnaire agonist symptom total score; higher scores indicate greater opioid symptom severity
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Title
Opioid withdrawal symptoms
Description
Opiate-32 questionnaire withdrawal symptom total score; higher scores indicate greater withdrawal severity
Time Frame
change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Tolan Park Medical Building
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Effects of Pharmacological Stress and rTMS on Executive Function in Opioid Use Disorder
We'll reach out to this number within 24 hrs