rTMS of Limbic Circuitry in Stress Modulation in Healthy Volunteers (TSM-1)

April 10, 2023 updated by: Mark Greenwald, PhD, Wayne State University

Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) of Limbic Brain Circuitry in Stress Modulation in a Healthy Population

This study will be conducted with healthy male and female participants. Aim 1 will determine during sham repetitive transcranial magnetic stimulation (rTMS) how a drug stressor combination (yohimbine + hydrocortisone) relative to placebo alters : (1a) impulsivity; (1b) mood; and (1c) physiology. Aim 2 will determine whether active rTMS over the medial prefrontal cortex alters the effects of stress-exposure on (2a) decision-making, (2b) mood, and (2c) biomarkers of stress.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study will use a double-blind, within-subjects randomized crossover design. Each participant will complete 4 sessions in this two-factor (2x2) combinatorial design: 1Hz medial prefrontal cortex (mPFC) vs. sham repetitive transcranial magnetic stimulation (rTMS) X pharmacological stressor (yohimbine 54mg + hydrocortisone 20mg) vs. placebo, with each session separated by at least 1 week. Participants will be asked not to use alcohol or drugs for 24-hr before arriving at the lab. We expect to complete screen at least 20 individuals to complete 12 individuals in this study. Candidates will first undergo psychiatric and medical screening to rule out contraindications to participation. Once enrolled, each participant will complete, in randomized order, the 4 conditions above. Periodic measures will be collected before and after the rTMS/sham and stress/placebo interventions. These measures will include subjective, behavioral and physiological assessments, as well as saliva and blood samples.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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 must be within ranges that allow for safe use of 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 (excluding marijuana) based on Timeline Followback interview
  • Urine positive for opioids, cocaine metabolites, benzodiazepines, barbiturates, amphetamines or pregnancy
  • Medical conditions prohibiting use of rTMS (e.g. seizure history; using validated rTMS screening instrument)
  • Lifetime diagnosis of: psychotic disorder, bipolar disorder, generalized anxiety disorder, obsessive compulsive disorder, or major depression that is not substance-induced
  • Past-year substance use disorder
  • Medical 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
  • Taken part in any research studies in the past month

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: placebo stressor, sham rTMS
placebo stressor is lactose, and sham rTMS is inactive figure of 8 coil
Drug: Placebo oral tablet
placebo stressor
Device: sham rTMS
sham mPFC rTMS
Experimental: placebo stressor, active rTMS
placebo stressor is lactose, and active rTMS is 1Hz stimulation over the medial prefrontal cortex
Drug: Placebo oral tablet
placebo stressor
Device: medial prefrontal cortex rTMS
1 Hz mPFC rTMS
Experimental: active stress, sham rTMS
active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and sham rTMS is inactive figure of 8 coil
Device: sham rTMS
sham mPFC rTMS
Drug: yohimbine + hydrocortisone
yohimbine 54mg + hydrocortisone 20mg oral
Experimental: active stress, active rTMS
active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and active rTMS is 1Hz stimulation over the medial prefrontal cortex
Device: medial prefrontal cortex rTMS
1 Hz mPFC rTMS
Drug: yohimbine + hydrocortisone
yohimbine 54mg + hydrocortisone 20mg oral

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Color-Word Stroop Task
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
reaction time (msec) measure of cognitive interference
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Digit Span Task
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
number of digits recalled, measure of verbal working memory
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Wisconsin Card Sorting Task
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
number of correct items, measure of ability to shift set and assesses cognitive flexibility
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Monetary Incentive Delay Task
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
number of rewards received, measure of motivation
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Delay Discounting Task
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
rate of monetary discounting
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Effort Choice Task
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
number of progressive ratio (PR) choices vs. fixed ratio (FR) choices
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Positive and Negative Affect Schedule (PANAS) positive affect
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
10-item questionnaire sub scale that measures positive affect
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Positive and Negative Affect Schedule (PANAS) negative affect
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
10-item questionnaire sub scale that measures negative affect
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
State-Trait Anxiety Inventory
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
questionnaire subscale that measures state anxiety
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Blood pressure
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Blood pressure (mm Hg)
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Heart rate
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Heart rate (beats/min)
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Saliva cortisol level
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Saliva cortisol level (µg/mL)
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Saliva alpha-amylase level
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Saliva alpha-amylase level (U/mL)
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Plasma prolactin level
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Plasma prolactin level (pg/mL)
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Plasma BDNF level
Time Frame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Plasma brain derived neurotrophic factor level (pg/mL)
change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wayne State University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 10, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 10, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 10, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 24, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 25, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 29, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 13, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TSM-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Full sharing plan is being developed.

IPD Sharing Time Frame

Materials will only become available after the study is completed and the first manuscript from this project is published.

IPD Sharing Access Criteria

Qualified investigators may apply in writing to Dr. Greenwald

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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