NCT06034496

Cranial Electrotherapy Stimulation and Acute Stress

Completed NA Results posted Last updated 15 September 2025

What this trial tests

NA trial testing Active CES in Anxiety State in 76 participants. Completed in 14 November 2024.

Timeline

12 September 2023

Primary endpoint
14 November 2024

14 November 2024

Quick facts

Lead sponsor	Tufts University
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	basic science
Enrollment	76
Start date	12 September 2023
Primary completion	14 November 2024
Estimated completion	14 November 2024
Sites	1 location across United States

Drugs / interventions tested

• Active CES
• Sham CES

Conditions studied

• Anxiety State — all drugs for Anxiety State →

Sponsor

Tufts University

Who can join

Adults 18 to 40, any sex, with Anxiety State. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Heart Rate During Stressful Lethal Force Decision Making Task Primary · Baseline and follow-up session after 20 CES to be completed within 4-6weeks

heart rate will be measured in beats per minute.

Baseline

Group	Value	95% CI
Active CES	98.5	± 16.1
Sham CES	111	± 19.5

Follow-up

Group	Value	95% CI
Active CES	100.0	± 13.5
Sham CES	114	± 20.1

Change From Baseline in Respiration Rate During Stressful Lethal Force Decision Making Task Primary · Baseline and follow-up session after 20 CES to be completed within 4-6weeks

respiration rate will be measured in breaths per minute.

Baseline

Group	Value	95% CI
Active CES	16.2	± 3.52
Sham CES	17.7	± 3.53

Follow-up

Group	Value	95% CI
Active CES	17.3	± 3.05
Sham CES	16.8	± 3.22

Change From Baseline in Heart Rate Variability During Stressful Lethal Force Decision Making Task Primary · Baseline and follow-up session after 20 CES to be completed within 4-6weeks

Heart rate variability will be measured in RMSSD.

Baseline

Group	Value	95% CI
Active CES	13.0	± 5.17
Sham CES	11.2	± 4.53

Follow-up

Group	Value	95% CI
Active CES	12.0	± 4.76
Sham CES	10.5	± 4.74

Change Over Time in Cortisol During Stressful Lethal Force Decision Making Task Primary · 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.

Baseline Pre

Group	Value	95% CI
Active CES	.293	± .137
Sham CES	.415	± .183

Baseline 0min post

Group	Value	95% CI
Active CES	.54	± .36
Sham CES	.399	± .105

Baseline 20min post

Group	Value	95% CI
Active CES	.57	± .396
Sham CES	.655	± .476

Baseline 40min post

Group	Value	95% CI
Active CES	.371	± .194
Sham CES	.456	± .252

Baseline 60min post

Group	Value	95% CI
Active CES	.29	± .156
Sham CES	.369	± .197

Follow-up Pre

Group	Value	95% CI
Active CES	.335	± .149
Sham CES	.345	± .123

Follow-up 0min post

Group	Value	95% CI
Active CES	.644	± .433
Sham CES	.556	± .296

Follow-up 20min post

Group	Value	95% CI
Active CES	.444	± .206
Sham CES	.534	± .292

Change Over Time in Alpha Amylase During Stressful Lethal Force Decision Making Task Primary · 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.

Baseline Pre

Group	Value	95% CI
Active CES	118	± 90.6
Sham CES	79.1	± 69.2

Baseline 0min post

Group	Value	95% CI
Active CES	144	± 91.3
Sham CES	131	± 121

Baseline 20min post

Group	Value	95% CI
Active CES	88.6	± 50.6
Sham CES	84	± 61

Baseline 40min post

Group	Value	95% CI
Active CES	110	± 87.6
Sham CES	78.1	± 58.2

Baseline 60min post

Group	Value	95% CI
Active CES	105	± 66.2
Sham CES	79.8	± 61.2

Follow-up Pre

Group	Value	95% CI
Active CES	68.4	± 51.0
Sham CES	61.7	± 48.6

Follow-up 0min post

Group	Value	95% CI
Active CES	99.8	± 39.3
Sham CES	129	± 101

Follow-up 20min post

Group	Value	95% CI
Active CES	110	± 71.8
Sham CES	90.8	± 72.6

Change Over Time in State Trait Anxiety Inventory (STAI) Scores at Each Session From Baseline to Follow-up Primary · 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.

STAT-T at baseline Pre CES intervention

Group	Value	95% CI
Active CES	33.71	± 10.75
Sham CES	29.52	± 7.28

STAT-T at follow-up Post CES intervention

Group	Value	95% CI
Active CES	33.33	± 12.72
Sham CES	32.64	± 7.16

STAI-S Baseline Session Pre-Stress task

Group	Value	95% CI
Active CES	33.4	± 7.94
Sham CES	31.0	± 6.62

STAI-S Baseline Session 0min Post Stress task

Group	Value	95% CI
Active CES	39.5	± 10.7
Sham CES	41.6	± 12.2

STAI-S Baseline Session 20min Post Stress task

Group	Value	95% CI
Active CES	35.6	± 11.5
Sham CES	34.1	± 9.53

STAI-S Baseline Session 40min Post Stress task

Group	Value	95% CI
Active CES	32.4	± 9.79
Sham CES	30.6	± 8.54

STAI-S Baseline Session 60min Post Stress task

Group	Value	95% CI
Active CES	30.9	± 9.56
Sham CES	29.1	± 6.66

STAI-S Follow-up Session Pre Stress task

Group	Value	95% CI
Active CES	33.8	± 15.0
Sham CES	27.6	± 8.55

Change From Baseline in Recognition Memory Primary · 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.

Baseline

Group	Value	95% CI
Active CES	77.1	± 11
Sham CES	80	± 12.2

Follow-up

Group	Value	95% CI
Active CES	78.2	± 15.9
Sham CES	76.7	± 14.3

Change From Baseline in Spatial Orientation Primary · 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.

Baseline

Group	Value	95% CI
Active CES	20.7	± 8.12
Sham CES	18.8	± 10.4

Follow-up

Group	Value	95% CI
Active CES	21.2	± 12.7
Sham CES	16.3	± 10.1

Change From Baseline in Decision Making Accuracy Primary · 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.

Baseline

Group	Value	95% CI
Active CES	3.64	± .681
Sham CES	3.89	± 1.08

Follow-up

Group	Value	95% CI
Active CES	4.48	± .943
Sham CES	4.75	± 1.29

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 year, 2 months. Reporting threshold: 0.6%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Active CES

Serious: 0/28 (0%)

Deaths: 0/28

Sham CES

Serious: 0/30 (0%)

Deaths: 0/30

Other adverse events (1 terms — click to expand)

Reaction	System	Active CES	Sham CES
Dizziness	General disorders	—	—

Data from ClinicalTrials.gov NCT06034496 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Effects of repeated cranial electrotherapy stimulation on physiological and behavioral responses to acute stress: a double-blind randomized clinical trial.
   Okano K, Lee MM, Hart-Pomerantz H, Smith M, et al · · 2025 · cited 1× · PMID 40881935 · DOI 10.3389/fnhum.2025.1641801