Cranial Electrotherapy Stimulation and Acute Stress

Cranial Electrotherapy Stimulation (CES) Influences on Acute Stress Responses

The goal of this study is to quantify the effects of 20 sessions of Cranial Electrotherapy Stimulation (CES) on measures of acute stress responses in Soldiers. The main question it aims to answer is how 20 sessions of CES will affect Soldiers' biochemical (salivary alpha amylase and cortisol), physiological (e.g., heart rate, heart rate variability, respiration rate), emotional (state anxiety), and behavioral (i.e., cognitive task performance) responses.

• On Day 1, participants will complete a baseline measure assessing their biochemical, physiological, emotional, and behavioral responses to a stressful lethal force decision making task.
• In the next four to six weeks, participants will complete 20 CES sessions.
• Within five days of completing the 20 CES sessions, participants will complete a follow-up measure assessing their biochemical, physiological, emotional, and behavioral responses to the same stressful lethal force decision making task they completed on Day 1.

Researchers will compare the Active CES group to the Sham CES group to see how 20 sessions of Active CES will affect the participants responses to their biochemical, physiological, emotional and behavioral responses relative to the Sham CES group.

Study Overview

• Status: Completed
• Conditions: Anxiety State
• Intervention / Treatment: Device: Active CES; Device: Sham CES

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Medford, Massachusetts, United States, 02155
      • Tufts University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18-40 years of age (17-40 if emancipated minor)
• Can sit and stand freely.
• Have not used or experienced CES administration in the past.
• Agree to have their data stored in a repository (database) for future use.

Exclusion Criteria:

• Use of prescription medications, other than oral contraceptives

• Women only:

  1. Pregnant or plan to become pregnant during the study
  2. Nursing

• History of:

  1. A neurological or psychological disorder (such as depression, anxiety disorders, migraines, cluster headaches, seizures, Post-traumatic stress disorder (PTSD) or panic attacks).
  2. Cardiac disease (including arrhythmia or fast or skipped heart beats).
  3. Implanted medical devices, such as pacemakers.
  4. Hypertension.
  5. Insomnia
  6. Head injury (including neurosurgery, concussion, TBI, skull fracture, hematoma)
  7. Illness that caused brain injury
  8. Any other brain-related condition (such as traumatic brain injury)
  9. Metal in the head (outside of mouth, such as shrapnel, surgical clips, or fragments from welding or metalwork)
  10. Implanted medical device (e.g., pacemaker, insulin pump)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active CES; Active Cranial Electrotherapy Stimulation (CES)	Device: Active CES; Active CES group will receive a minimum of 250µA and up to 500µA depending on thresholding, once daily for 20 days (over the course of 4~6 weeks), 20 minutes per day.; Other Names: Alpha-Stim
Sham Comparator: Sham CES; Sham Cranial Electrotherapy Stimulation (CES)	Device: Sham CES; Sham CES group will be identical to Active CES group with the exception of the device not administering any electrical current; Other Names: Alpha-Stim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Heart Rate During Stressful Lethal Force Decision Making Task	heart rate will be measured in beats per minute.	Baseline and follow-up session after 20 CES to be completed within 4-6weeks
Change From Baseline in Respiration Rate During Stressful Lethal Force Decision Making Task	respiration rate will be measured in breaths per minute.	Baseline and follow-up session after 20 CES to be completed within 4-6weeks
Change From Baseline in Heart Rate Variability During Stressful Lethal Force Decision Making Task	Heart rate variability will be measured in RMSSD.	Baseline and follow-up session after 20 CES to be completed within 4-6weeks
Change Over Time in Cortisol During Stressful Lethal Force Decision Making Task	Cortisol (µg/dL) will be measured through saliva samples. Saliva samples will be taken at five time points, approximately 20 minute increments during the baseline and follow-up sessions.	Baseline and follow-up session after 20 CES completed within 4-6weeks
Change Over Time in Alpha Amylase During Stressful Lethal Force Decision Making Task	Alpha amylase (IU) will be measured through saliva samples. Saliva samples will be taken at five time points, approximately 20 minute increments during the baseline and follow-up sessions.	Baseline and follow-up session after 20 CES completed within 4-6weeks
Change Over Time in State Trait Anxiety Inventory (STAI) Scores at Each Session From Baseline to Follow-up	STAI assesses both state and trait anxiety separately with each scale ranging from 20 to 80, with higher scores correlating with greater anxiety. STAI-S is the State Trait Anxiety Inventory - State version, and STAI-T is the State Trait Anxiety Inventory - Trait version.	At baseline, at each of the 20 CES sessions completed within 4-6weeks, and at follow-up to be completed within 5 days of last CES
Change From Baseline in Recognition Memory	Recognition memory of previously learned targets while ignoring visually similar distractor objects will be measured and evaluated with percent accuracy.	Baseline and follow-up session after 20 CES completed within 4-6weeks
Change From Baseline in Spatial Orientation	Spatial orientation task will involve pointing towards a series of distant (out of visible range) landmarks in the virtual environment and estimating distance to those landmarks. Spatial orientation will be calculated using mean absolute angular error. Larger numbers correlate with higher error.	Baseline and follow-up session after 20 CES completed within 4-6weeks
Change From Baseline in Decision Making Accuracy	Participants will make lethal force decision making by shooting at threatening targets and allowing non-threatening targets to pass. Decision making accuracy will be calculated using d prime. Higher d prime correlates with better accuracy.	Baseline and follow-up session after 20 CES completed within 4-6weeks
Change From Baseline in Decision Making Reaction Time	Participants will make lethal force decision making by shooting at threatening targets and allowing non-threatening targets to pass. Decision making reaction time to shoot at threatening targets will be measured in milliseconds.	Baseline and follow-up session after 20 CES completed within 4-6weeks

Collaborators and Investigators

• Sponsor: Tufts University
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Kana Okano, Ph.D., Tufts University

Publications and helpful links

General Publications

• Okano K, Lee MM, Hart-Pomerantz H, Smith M, Sandone MK, Harvey T, Brunye TT. Effects of repeated cranial electrotherapy stimulation on physiological and behavioral responses to acute stress: a double-blind randomized clinical trial. Front Hum Neurosci. 2025 Aug 13;19:1641801. doi: 10.3389/fnhum.2025.1641801. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2023
• Primary Completion (Actual): November 14, 2024
• Study Completion (Actual): November 14, 2024

Study Registration Dates

• First Submitted: August 18, 2023
• First Submitted That Met QC Criteria: September 5, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Cranial Electrotherapy Stimulation; Acute Stress
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: STUDY00003572

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Participants consent to having their deidentified data placed in a repository/shared upon protocol closure, however it is not mandated by the protocol or institution.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No