Assessing the Effects of Hormones on Noninvasive Transcranial Stimulation

NCT07635017 | Not Yet Recruiting FDA Device

• 1 other identifier: STUDY2026_00000239
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study is investigating how two types of non-invasive brain stimulation, transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS), affect brain activity, and whether combining them produces stronger or more consistent effects than either one used alone. The motivation for this comes from the observation that TMS, which is FDA-approved for treating depression, tends to work less well in postmenopausal women because lower estrogen levels reduce the brain's ability to respond to stimulation. The research team believes that pairing TMS with TES, which targets a different set of brain cells, may be able to overcome this hormonal barrier and make stimulation more effective. Participants will come into the lab for up to 24 visits over 8 months, beginning with an initial visit to establish the right stimulation settings, followed by a series of stimulation sessions in which brain activity is measured before and after receiving either TES, TMS, or both together. For female participants, sessions will be scheduled at specific points in the menstrual cycle to capture the natural monthly rise and fall of estrogen, while male participants will be scheduled on a comparable fixed interval as a comparison group. The insights gained from this study could directly inform the development of better, more reliable brain stimulation treatments for women with depression.

Conditions

Cortical Excitability; Healthy; TMS; Menopause; Menstrual Cycle

Keywords

Transcranial Magnetic Stimulation; Transcranial Electrical Stimulation; Noninvasive Neuromodulation; Perimenopause; Electromyography; Hormones; Cortical Excitability; Synaptic Plasticity

Outcome Measures

Primary Outcomes (1)

• Motor Evoked Potential Amplitude Change

  Motor evoked potential (MEP) amplitude is recorded via surface EMG electrodes placed on the upper or lower limb musculature in response to single-pulse diagnostic TMS delivered to the primary motor cortex (M1). MEP amplitude is measured as the peak-to-peak voltage of the evoked muscle response in millivolts. The primary outcome is the change in trial-averaged MEP amplitude from before to after a train of up to 2,000 pulses of TMS, TES, or combined TMS+TES. This delta is compared across two hormonal phases of the menstrual cycle - estrogen nadir (days 1-3) and the late follicular phase (days 10-14) - and across the three intervention arms. A larger positive delta indicates greater corticospinal excitability / synpatic potentiation following stimulation, while a negative delta indicates suppression of corticospinal excitability / synpatic potentiation.

  MEP recorded at the same time as the diagnostic TMS pre-intervention and post-intervention of the 2,000 pulse stimulation at every session for at most 8 months / 24 sessions. Delta/change assessed after each session.

Secondary Outcomes (4)

• Numerical Rating Scale

  Recorded at the same time as 2,000 pulses of stimulation (intraprocedurally) at every session after a block of "N" stim pulses for at most 8 months / 24 sessions. The number of stim pulses vary by intervention arm.

• Menstrual Phase Identification Questionnaire

  At most daily from enrollment to the end of intervention period (up to 8 months). Will be recorded online at an unspecified time during the experimental period depending on the participants preference.

• Paired Pulse Responses

  Immediately prior to intervention/Immediately post-intervention at every session for at most 24 sessions/8 months

• EMG responses

  Recorded at the same time as 2,000 pulses of stimulation (intraprocedurally) at every session for at most 8 months / 24 sessions.

Study Arms (3)

TES + TMS

EXPERIMENTAL

Participants receive concurrent TMS and TES stimulation delivered to the primary motor cortex (M1), with sessions scheduled at two points per menstrual cycle - once at estrogen nadir (days 1-3) and once during the late follicular phase (days 10-14). Prior to the stimulation train, diagnostic TMS measuring SICI, LICI, and ICF is conducted to establish baseline cortical excitability. Participants then undergo a train of up to 2,000 paired TMS and TES pulses, with a 1-3 ms latency maintained between the two modalities. Following the train, diagnostic TMS is repeated to assess changes in cortical excitability relative to baseline. Participants remain seated throughout the session.

Device: TES + TMS

TES

EXPERIMENTAL

Participants receive focal electrical stimulation delivered to the primary motor cortex (M1), with sessions scheduled at two points per menstrual cycle - once at estrogen nadir (days 1-3) and once during the late follicular phase (days 10-14). Prior to the stimulation train, diagnostic TMS measuring SICI, LICI, and ICF is conducted to establish baseline cortical excitability. Participants then undergo a train of up to 2,000 TES pulses, with timing, amplitude, and location varied to achieve targeted cortical stimulation. Following the train, diagnostic TMS is repeated to assess changes in cortical excitability relative to baseline. Participants remain seated throughout the session.

Device: Transcranial Electrical Stimulation

TMS

EXPERIMENTAL

Participants receive repetitive transcranial magnetic stimulation delivered to the primary motor cortex (M1), with sessions scheduled at two points per menstrual cycle - once at estrogen nadir (days 1-3) and once during the late follicular phase (days 10-14). Prior to the stimulation train, diagnostic TMS measuring SICI, LICI, and ICF is conducted to establish baseline cortical excitability. Participants then undergo a train of up to 2,000 pulses of standard rTMS or up to 600 pulses of iTBS (3 pulses at 50 Hz, burst repetition rate of 5 Hz, 2 seconds ON and 8 seconds OFF for 20 cycles at 80% motor threshold). Following the train, diagnostic TMS is repeated to assess changes in cortical excitability relative to baseline. Participants remain seated throughout the session.

Device: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation DEVICE

Transcranial magnetic stimulation (TMS) uses an electromagnetic coil placed over the scalp to deliver precisely timed magnetic pulses that induce electric fields in targeted cortical regions. By varying the frequency, intensity, and coil position, the system achieves non-invasive stimulation of specific brain areas. Investigators will use the DuoMag XT-100 rTMS system manufactured by DEYMED Diagnostic. The device is a CE-certified Class IIa medical device intended for use in human research and clinical applications. The DuoMag XT-100 delivers both monophasic and biphasic pulses with a total pulse duration of 290 µs and a maximum discharge energy of 265 J, capable of stimulating at 100% intensity at 22 Hz and up to 100 Hz at less than 50% intensity.

TMS

TES + TMS DEVICE

The combined TMS+TES intervention delivers concurrent transcranial magnetic and electrical stimulation using the DuoMag XT-100 rTMS system and the Digitimer DS8R/DS5 current stimulators simultaneously. The DuoMag XT-100 is a CE-certified Class IIa device manufactured by DEYMED Diagnostic, delivering monophasic and biphasic pulses with a 290 µs pulse duration and 265 J maximum discharge energy, capable of 100% intensity at 22 Hz and up to 100 Hz at less than 50% intensity. The Digitimer DS8R/DS5 are CE-certified stimulators delivering brief duration (50-2000 µs) current pulses via surface electrodes, with current output adjustable from 0mA to 1000mA, compliance voltage up to 400V, and energy limit of 300mJ. Standard adhesive electrodes are replaced with Soterix Sintered Ag/AgCl ring electrodes featuring radial slits to impede induced eddy currents. Magnetic pulses are delivered via the DuoMag 70BF liquid-cooled butterfly coil. Pulses are interleaved with a 1-3 ms latency.

TES + TMS

Transcranial Electrical Stimulation DEVICE

SharpFocus transcranial electrical stimulation (TES) uses a multichannel stimulator connected to a scalp electrode to deliver precisely timed, intensity-modulated electrical pulses. By varying the timing, amplitude, and location of these pulses, the system achieves focal stimulation of targeted cortical regions. Investigators will use Digitimer DS8R and/or Digitimer DS5 current stimulators to apply all current stimuli. These stimulators are CE certified and are intended for use in human research applications. The stimulator safely delivers brief duration (50-2000µs) current pulses for transcranial electrical stimulation and activation of nerves and muscles via surface electrodes. The current output of the DS8R is adjustable over the range 0mA to 1000mA, with a compliance voltage of up to 400V and an energy limit of 300mJ.

TES

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: While all genders are able to enroll in this study, men will only serve as a comparator/control group. Only females with regular menstrual periods will be used to directly analyze changes in motor evoked potentials.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 and 40 years old
• Female subjects must have regular menstrual cycles (defined as a cycle that occurs at predictable intervals, typically between 24 and 38-days length) via self-report

You may not qualify if:

• Allergies to henna
• Allergies to gel used for electrodes
• History of seizures or epilepsy
• Subjects must not have any serious disease, disorder, infection, or cognitive impairments that could affect their ability to participate in this study.
• Female subjects of child-bearing potential must not be pregnant
• Subjects must not have any implanted stimulators or pulse generators
• Subjects must not have heart disease, including known arrhythmia
• Subjects must not have any metal implants in their head

Sponsors & Collaborators

• Carnegie Mellon University: lead

Study Sites (1)

Carnegie Mellon University

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Interventions

Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques; Magnetic Field Therapy

Central Study Contacts

Pulkit Grover

CONTACT

412-268-3644; pgrover@andrew.cmu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 29, 2026
• First Posted: June 9, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: June 9, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)