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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04180969
Recruitment Status : Not yet recruiting
First Posted : November 29, 2019
Last Update Posted : April 27, 2022
Sponsor:
Information provided by (Responsible Party):
Mark Greenwald, PhD, Wayne State University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Stress Healthy Drug: yohimbine + hydrocortisone Device: medial prefrontal cortex rTMS Drug: Placebo oral tablet Device: sham rTMS Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Double-blind, 1Hz mPFC (vs. sham) rTMS X stressor (vs. placebo), 4-session, within-subjects, randomized crossover design
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: sham (inactive) figure of 8 coil for rTMS, and placebo for pharmacological stressor
Primary Purpose: Basic Science
Official Title: Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) of Limbic Brain Circuitry in Stress Modulation in a Healthy Population
Estimated Study Start Date : January 2023
Estimated Primary Completion Date : October 30, 2023
Estimated Study Completion Date : December 31, 2023

Arm Intervention/treatment
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
Device: medial prefrontal cortex rTMS
1 Hz mPFC rTMS

Drug: Placebo oral tablet
placebo stressor

Experimental: active stress, sham rTMS
active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and sham rTMS is inactive figure of 8 coil
Drug: yohimbine + hydrocortisone
yohimbine 54mg + hydrocortisone 20mg oral

Device: sham rTMS
sham mPFC rTMS

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
Drug: yohimbine + hydrocortisone
yohimbine 54mg + hydrocortisone 20mg oral

Device: medial prefrontal cortex rTMS
1 Hz mPFC rTMS




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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)

  11. 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)

  12. 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)

  13. 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)

  14. 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)

  15. 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)



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04180969


Contacts
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Contact: Tabitha Moses 313-577-8257 druglabdetroit@gmail.com
Contact: Mark K Greenwald, PhD 313-993-3965 mgreen@med.wayne.edu

Sponsors and Collaborators
Wayne State University
Investigators
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Study Director: Mark K Greenwald, PhD Wayne State University
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Responsible Party: Mark Greenwald, PhD, Professor, Wayne State University
ClinicalTrials.gov Identifier: NCT04180969    
Other Study ID Numbers: TSM-1
First Posted: November 29, 2019    Key Record Dates
Last Update Posted: April 27, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Full sharing plan is being developed.
Supporting Materials: Study Protocol
Time Frame: Materials will only become available after the study is completed and the first manuscript from this project is published.
Access Criteria: Qualified investigators may apply in writing to Dr. Greenwald

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hydrocortisone
Yohimbine
Anti-Inflammatory Agents
Mydriatics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-2 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Urological Agents