Anxiety StateNCT06034496

Cranial Electrotherapy Stimulation and Acute Stress

A study testing Active CES in people with Anxiety State, run by Tufts University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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.… Read more about this study

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: Anxiety State
What is being tested?: Active CES
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 76 participants
Where: 1 siteUnited States
Study dates: 12 Sep 2023to 14 Nov 2024
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 40 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

Use of prescription medications, other than oral contraceptives
Women only:
Pregnant or plan to become pregnant during the study
Nursing
History of:
A neurological or psychological disorder (such as depression, anxiety disorders, migraines, cluster headaches, seizures, Post-traumatic stress disorder (PTSD) or panic attacks).

Show all 15Show fewer

Cardiac disease (including arrhythmia or fast or skipped heart beats).
Implanted medical devices, such as pacemakers.
Hypertension.
Insomnia
Head injury (including neurosurgery, concussion, TBI, skull fracture, hematoma)
Illness that caused brain injury
Any other brain-related condition (such as traumatic brain injury)
Metal in the head (outside of mouth, such as shrapnel, surgical clips, or fragments from welding or metalwork)
Implanted medical device (e.g., pacemaker, insulin pump)

Trial locations and contacts

1 site in 1 country.

United States1 site

Tufts University
Medford, Massachusetts, 02155

Other trials in United States

About this study

Official title: Cranial Electrotherapy Stimulation (CES) Influences on Acute Stress 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.

Conditions: Anxiety State
Being tested: Active CES, Sham CES
Keywords: Cranial Electrotherapy Stimulation, Acute Stress
Medical subject headings: Anxiety Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Active CESDevice
Also called Alpha-Stim
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.
Sham CESDevice
Also called Alpha-Stim
Sham CES group will be identical to Active CES group with the exception of the device not administering any electrical current

Study groups in NCT06034496
Study group	Role	What they receive
Active CES	Active comparator	Active Cranial Electrotherapy Stimulation (CES) Receives: Device: Active CES
Sham CES	Sham comparator	Sham Cranial Electrotherapy Stimulation (CES) Receives: Device: Sham CES

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Heart Rate During Stressful Lethal Force Decision Making Task
heart rate will be measured in beats per minute.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and follow-up session after 20 CES completed within 4-6weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Sep 202314 Nov 2024

First posted13 Sep 2023
Study start12 Sep 2023
Primary completion14 Nov 2024
Study completion14 Nov 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Anxiety StateStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 76 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06034496
Sponsor's protocol ID: STUDY00003572
Status last verified: Sep 2025
First submitted: 18 Aug 2023
Last updated: 15 Sep 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: Undecided: 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.

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.
PubMed 40881935

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Cranial Electrotherapy Stimulation (CES) Influences on Acute Stress Responses
ClinicalTrials.gov ID: NCT06034496
Acronym / sponsor ID: STUDY00003572
Conditions: Anxiety State
Keywords: Cranial Electrotherapy Stimulation, Acute Stress
Study type: Interventional
Recruitment status: Completed
Enrolment: 76 participants (actual)
Lead sponsor: Tufts UniversityUniversity, hospital or other
Collaborators: United States Department of Defense
Study start: 12 Sep 2023 (actual)
Primary completion: 14 Nov 2024 (actual)
Study completion: 14 Nov 2024 (actual)
First posted: 13 Sep 2023 (actual)
Results: Posted 17 Jun 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Active CES	Active comparator	Device: Active CESActive Cranial Electrotherapy Stimulation (CES)
Sham CES	Sham comparator	Device: Sham CESSham Cranial Electrotherapy Stimulation (CES)

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (15 listed)

Use of prescription medications, other than oral contraceptives
Women only:
History of:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Active CESAlso: Alpha-StimActive 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.	Device	Active CES
Sham CESAlso: Alpha-StimSham CES group will be identical to Active CES group with the exception of the device not administering any electrical current	Device	Sham CES

Primary outcome

Change From Baseline in Heart Rate During Stressful Lethal Force Decision Making Task
Time frame: Baseline and follow-up session after 20 CES to be completed within 4-6weeks
heart rate will be measured in beats per minute.
Change From Baseline in Respiration Rate During Stressful Lethal Force Decision Making Task
Time frame: Baseline and follow-up session after 20 CES to be completed within 4-6weeks
respiration rate will be measured in breaths per minute.
Change From Baseline in Heart Rate Variability During Stressful Lethal Force Decision Making Task
Time frame: Baseline and follow-up session after 20 CES to be completed within 4-6weeks
Heart rate variability will be measured in RMSSD.
Change Over Time in Cortisol During Stressful Lethal Force Decision Making Task
Time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
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.
Change Over Time in Alpha Amylase During Stressful Lethal Force Decision Making Task
Time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
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.
Change Over Time in State Trait Anxiety Inventory (STAI) Scores at Each Session From Baseline to Follow-up
Time frame: 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
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.
Change From Baseline in Recognition Memory
Time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
Recognition memory of previously learned targets while ignoring visually similar distractor objects will be measured and evaluated with percent accuracy.
Change From Baseline in Spatial Orientation
Time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
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.
Change From Baseline in Decision Making Accuracy
Time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
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.
Change From Baseline in Decision Making Reaction Time
Time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
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.

Results and safety

Results posted to the registry on 17 Jun 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Active CES	28	21
Sham CES	30	25

Primary outcome: Change From Baseline in Heart Rate During Stressful Lethal Force Decision Making Task

Time frame: Baseline and follow-up session after 20 CES to be completed within 4-6weeks. Mean (Standard Deviation). Unit: bpm

Measure	Active CES n = 18	Sham CES n = 19
Baseline	98.5 (16.1)	111 (19.5)
Follow-up	100.0 (13.5)	114 (20.1)

Active CES vs Sham CES: p = .012, ANOVA
Active CES vs Sham CES: p = .33, ANOVA
Active CES vs Sham CES: p = .85, ANOVA

Population analysed: Due to technical issues, we were unable to collect data from 9 participants.

Primary outcome: Change From Baseline in Respiration Rate During Stressful Lethal Force Decision Making Task

Time frame: Baseline and follow-up session after 20 CES to be completed within 4-6weeks. Mean (Standard Deviation). Unit: breath per minute

Measure	Active CES n = 18	Sham CES n = 19
Baseline	16.2 (3.52)	17.7 (3.53)
Follow-up	17.3 (3.05)	16.8 (3.22)

Active CES vs Sham CES: p = .6, ANOVA
Active CES vs Sham CES: p = .9, ANOVA
Active CES vs Sham CES: p = .05, ANOVA

Primary outcome: Change From Baseline in Heart Rate Variability During Stressful Lethal Force Decision Making Task

Time frame: Baseline and follow-up session after 20 CES to be completed within 4-6weeks. Mean (Standard Deviation). Unit: bpm

Measure	Active CES n = 18	Sham CES n = 19
Baseline	13.0 (5.17)	11.2 (4.53)
Follow-up	12.0 (4.76)	10.5 (4.74)

Active CES vs Sham CES: p = .26, ANOVA
Active CES vs Sham CES: p = .17, ANOVA
Active CES vs Sham CES: p = .73, ANOVA

Primary outcome: Change Over Time in Cortisol During Stressful Lethal Force Decision Making Task

Time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks. Mean (Standard Deviation). Unit: µg/dL

Measure	Active CES n = 21	Sham CES n = 25
Baseline Pre	.293 (.137)	.415 (.183)
Baseline 0min post	.54 (.36)	.399 (.105)
Baseline 20min post	.57 (.396)	.655 (.476)
Baseline 40min post	.371 (.194)	.456 (.252)
Baseline 60min post	.29 (.156)	.369 (.197)
Follow-up Pre	.335 (.149)	.345 (.123)
Follow-up 0min post	.644 (.433)	.556 (.296)
Follow-up 20min post	.444 (.206)	.534 (.292)

Active CES vs Sham CES: p = .18, ANOVA
Active CES vs Sham CES: p = .00, ANOVA
Active CES vs Sham CES: p = .53, ANOVA

Adverse events

Time frame: 1 year, 2 months. Other adverse events reported at 0.6% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Active CES	0 of 28 (0%)	2 of 28 (7.1%)	0 of 28
Sham CES	0 of 30 (0%)	2 of 30 (6.7%)	0 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40881935Okano 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.
Individual participant dataSharing planned: Undecided. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kana Okano, Ph.D. principal investigator

Tufts University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Active CES in people with Anxiety State, run by Tufts University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Heart Rate During Stressful Lethal Force Decision Making Task (time frame: Baseline and follow-up session after 20 CES to be completed within 4-6weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06034496, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2025.