rTMS of Limbic Circuitry in Stress Modulation in Healthy Volunteers

Healthy Clinical Trial

— TSM-1  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04180969
• Other study ID #: TSM-1
• Status: Withdrawn
• Phase: Phase 2
• Start date: April 10, 2023
• Est. completion date: April 10, 2023

Study information

• Verified date: April 2023
• Source: Wayne State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 10, 2023
• Est. primary completion date: April 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy
• Stress

Intervention

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

Device:
• medial prefrontal cortex rTMS
1 Hz mPFC rTMS

Drug:
• Placebo oral tablet
placebo stressor

Device:
• sham rTMS
sham mPFC rTMS

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wayne State University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Color-Word Stroop Task	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)
Primary	Digit Span Task	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)
Primary	Wisconsin Card Sorting Task	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)
Primary	Monetary Incentive Delay Task	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)
Primary	Delay Discounting Task	rate of monetary discounting	change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Primary	Effort Choice Task	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)
Primary	Positive and Negative Affect Schedule (PANAS) positive affect	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)
Primary	Positive and Negative Affect Schedule (PANAS) negative affect	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)
Primary	State-Trait Anxiety Inventory	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)
Primary	Blood pressure	Blood pressure (mm Hg)	change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Primary	Heart rate	Heart rate (beats/min)	change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Primary	Saliva cortisol level	Saliva cortisol level (µg/mL)	change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Primary	Saliva alpha-amylase level	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)
Primary	Plasma prolactin level	Plasma prolactin level (pg/mL)	change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Primary	Plasma BDNF level	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)