StressPhase 2TSM-1NCT04180969

rTMS of Limbic Circuitry in Stress Modulation in Healthy Volunteers

A Phase 2 study testing yohimbine + hydrocortisone and medial prefrontal cortex rTMS in people with Stress and Healthy, run by Wayne State University.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 21 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Stress, Healthy
What is being tested?: yohimbine + hydrocortisone and medial prefrontal cortex rTMS
Type of treatment: Pill or oral medicine, Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 0 participants
Where: No sites listed yet
Study dates: 10 Apr 2023to 10 Apr 2023
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Show all 11Show fewer

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

About this study

Official title: 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.

Read the 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.

Conditions: Stress, Healthy
Being tested: yohimbine + hydrocortisone, medial prefrontal cortex rTMS, Placebo oral tablet, sham rTMS

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

yohimbine + hydrocortisoneDrug
yohimbine 54mg + hydrocortisone 20mg oral
medial prefrontal cortex rTMSDevice
1 Hz mPFC rTMS
Placebo oral tabletDrug
placebo stressor
sham rTMSDevice
sham mPFC rTMS

Study groups in NCT04180969
Study group	Role	What they receive
placebo stressor, sham rTMS	Placebo comparator	placebo stressor is lactose, and sham rTMS is inactive figure of 8 coil Receives: Drug: Placebo oral tablet; Device: sham rTMS
placebo stressor, active rTMS	Experimental	placebo stressor is lactose, and active rTMS is 1Hz stimulation over the medial prefrontal cortex Receives: Device: medial prefrontal cortex rTMS; Drug: Placebo oral tablet
active stress, sham rTMS	Experimental	active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and sham rTMS is inactive figure of 8 coil Receives: Drug: yohimbine + hydrocortisone; Device: sham rTMS
active stress, active rTMS	Experimental	active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and active rTMS is 1Hz stimulation over the medial prefrontal cortex Receives: Drug: yohimbine + hydrocortisone; Device: medial prefrontal cortex rTMS

What is being measured

The primary outcome is the main question the study is designed to answer.

Color-Word Stroop Task
reaction time (msec) measure of cognitive interference
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Digit Span Task
number of digits recalled, measure of verbal working memory
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Wisconsin Card Sorting Task
number of correct items, measure of ability to shift set and assesses cognitive flexibility
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Monetary Incentive Delay Task
number of rewards received, measure of motivation
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Delay Discounting Task
rate of monetary discounting
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Effort Choice Task
number of progressive ratio (PR) choices vs. fixed ratio (FR) choices
Measured: 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
10-item questionnaire sub scale that measures positive affect
Measured: 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
10-item questionnaire sub scale that measures negative affect
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
State-Trait Anxiety Inventory
questionnaire subscale that measures state anxiety
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Blood pressure
Blood pressure (mm Hg)
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Heart rate
Heart rate (beats/min)
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Saliva cortisol level
Saliva cortisol level (µg/mL)
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Saliva alpha-amylase level
Saliva alpha-amylase level (U/mL)
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Plasma prolactin level
Plasma prolactin level (pg/mL)
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Plasma BDNF level
Plasma brain derived neurotrophic factor level (pg/mL)
Measured: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Apr 202310 Apr 2023

First posted29 Nov 2019
Study start10 Apr 2023
Primary completion10 Apr 2023
Study completion10 Apr 2023

Why it stopped: Lack of funding

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for StressStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Model description: Double-blind, 1Hz mPFC (vs. sham) rTMS X stressor (vs. placebo), 4-session, within-subjects, randomized crossover design
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04180969
Sponsor's protocol ID: TSM-1
Acronym: TSM-1
Status last verified: Apr 2023
First submitted: 24 Nov 2019
Last updated: 13 Apr 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Full sharing plan is being developed.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 13 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) of Limbic Brain Circuitry in Stress Modulation in a Healthy Population
ClinicalTrials.gov ID: NCT04180969
Acronym / sponsor ID: TSM-1 / TSM-1
Conditions: Stress, Healthy
Phase: Phase 2
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Lack of funding
Enrolment: 0 participants (actual)
Lead sponsor: Wayne State UniversityUniversity, hospital or other
Study start: 10 Apr 2023 (actual)
Primary completion: 10 Apr 2023 (actual)
Study completion: 10 Apr 2023 (actual)
First posted: 29 Nov 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4
Model description: Double-blind, 1Hz mPFC (vs. sham) rTMS X stressor (vs. placebo), 4-session, within-subjects, randomized crossover design

Arm	Type	Receives
placebo stressor, sham rTMS	Placebo comparator	Drug: Placebo oral tablet, Device: sham rTMSplacebo stressor is lactose, and sham rTMS is inactive figure of 8 coil
placebo stressor, active rTMS	Experimental	Device: medial prefrontal cortex rTMS, Drug: Placebo oral tabletplacebo stressor is lactose, and active rTMS is 1Hz stimulation over the medial prefrontal cortex
active stress, sham rTMS	Experimental	Drug: yohimbine + hydrocortisone, Device: sham rTMSactive stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and sham rTMS is inactive figure of 8 coil
active stress, active rTMS	Experimental	Drug: yohimbine + hydrocortisone, Device: medial prefrontal cortex rTMSactive stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and active rTMS is 1Hz stimulation over the medial prefrontal cortex

Who may qualify

Ages: 21 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
yohimbine + hydrocortisoneyohimbine 54mg + hydrocortisone 20mg oral	Drug	active stress, active rTMS, active stress, sham rTMS
medial prefrontal cortex rTMS1 Hz mPFC rTMS	Device	active stress, active rTMS, placebo stressor, active rTMS
Placebo oral tabletplacebo stressor	Drug	placebo stressor, active rTMS, placebo stressor, sham rTMS
sham rTMSsham mPFC rTMS	Device	active stress, sham rTMS, placebo stressor, sham rTMS

Primary outcome

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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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)
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)

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2023.
Individual participant dataSharing planned: Yes. Full sharing plan is being developed.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mark K Greenwald, PhD study director

Wayne State University

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing yohimbine + hydrocortisone and medial prefrontal cortex rTMS in people with Stress and Healthy, run by Wayne State University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 13 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04180969.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2023.