Clinical trial NCT04180969: rTMS of Limbic Circuitry in Stress Modulation in Healthy Volunteers
Official title: Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) of Limbic Brain Circuitry in Stress Modulation in a Healthy Population
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Stress
Healthy
Lead sponsor: Wayne State University
Sponsor class: OTHER
First posted: 2019-11-29
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, 1Hz mPFC (vs. sham) rTMS X stressor (vs. placebo), 4-session, within-subjects, randomized crossover design
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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

Primary outcomes:
measure: Color-Word Stroop Task
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Digit Span Task
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Wisconsin Card Sorting Task
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Monetary Incentive Delay Task
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Delay Discounting Task
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Effort Choice Task
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Positive and Negative Affect Schedule (PANAS) positive affect
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Positive and Negative Affect Schedule (PANAS) negative affect
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: State-Trait Anxiety Inventory
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Blood pressure
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Heart rate
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Saliva cortisol level
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Saliva alpha-amylase level
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Plasma prolactin level
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
measure: Plasma BDNF level
timeFrame: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Wayne State University
name: Mark K Greenwald, PhD
role: STUDY_DIRECTOR
References: