Cranial Electrotherapy Stimulation and Brain Imaging for Gulf War Syndrome

NCT07151248 | Recruiting DMC FDA Device

• 4 other identifiers: STUDY000098102025P011630CDMRP-TX240208CDMRP-TX240208P1
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of the proposed study is to critically evaluate a nonpharmacological and readily available therapy, cranial electrical stimulation (CES) using Alpha-Stim™, and to discover the brain function mechanisms underlying Gulf War Illness-related Headache and Pain (GWI-HAP) and treatment response to CES. For this objective, the investigators will employ an adaptive trial design as well as a neuroimaging technique using MRI, which has become the pre-eminent technique for assessing the integrity of brain function, connectivity, and organization in healthy brain and pathology.

Conditions

Gulf War Syndrome

Keywords

Gulf War Illness Headaches and Pain

Outcome Measures

Primary Outcomes (3)

• Change in Defense and Veterans Pain Rating Scale (DVPRS) from baseline

  The Defense and Veterans Pain Rating Scale (DVPRS) is a pain assessment tool. Patients will rate their pain intensity on a scale of 0 to 10, where 0 is no pain and 10 is the worst imaginable pain.

  Baseline, 6 and 12 weeks post-intervention

• Change in Brief Pain Inventory (BPI) severity subscale from baseline

  The BPI assesses pain severity and interference with function. The pain severity subscale consists of 4 items, each rated on a 0-10 numerical scale (0 = "no pain," 10 = "pain as bad as you can imagine"). Scores are averaged to yield a total range of 0-10. Lower scores reflect less severe pain and are considered favorable outcomes.

  Baseline, 6 and 12 weeks post-intervention

• Change in Brief Pain Inventory (BPI) pain interference subscale from baseline

  The pain interference subscale consists of 7 items rated on a 0-10 numerical scale (0 = "does not interfere," 10 = "completely interferes"), assessing the impact of pain on daily activities such as mood, walking ability, work, and enjoyment of life. Scores are averaged to create a total range of 0-10. Lower scores reflect less interference from pain and are considered favorable outcomes.

  Baseline, 6 and 12 weeks post-intervention

Secondary Outcomes (17)

• Change in sit-to-stand/chair stand test

  Baseline, 6 and 12 weeks post-intervention

• Change in bicep(arm) curls

  Baseline, 6 and 12 weeks post-intervention

• Change in handgrip strength

  Baseline, 6 and 12 weeks post-intervention

• Change in finger-tap test

  Baseline, 6 and 12 weeks post-intervention

• Change in Patient-Reported Outcomes Measurement Information System (PROMIS): sleep score

  Baseline, 6 and 12 weeks post-intervention

Study Arms (3)

True CES therapy

EXPERIMENTAL

The participant will be trained in device usage and instructed to use the device each evening around the same time for 60 minutes (timer will be pre-set). The intervention (true CES) will occur over the course of 6 weeks.

Device: Cranial electrical/electrotherapy stimulation (CES)

Sham CES therapy

SHAM COMPARATOR

The participant will be trained in device usage and instructed to use the device each evening around the same time for 60 minutes (timer will be pre-set). The intervention (sham CES) will occur over the course of 6 weeks.

Device: Sham Cranial electrical/electrotherapy stimulation (CES)

True CES therapy for non-responders

EXPERIMENTAL

For the non-responders (\<2 point decrease on DVPRS), the blind will be broken, and those non-responder participants who were initially assigned to sham placebo CES during the first 6 weeks of the intervention, now will be offered the opportunity to utilize the true CES device in a modified sequential parallel comparison design for an additional 6 weeks.

Device: Cranial electrical/electrotherapy stimulation (CES)

Interventions

Cranial electrical/electrotherapy stimulation (CES) DEVICE

Cranial electrical/electrotherapy stimulation (CES) is a non-pharmacological, portable, non-invasive intervention. Active research units will be locked at the specified amplitude and administer that amplitude of stimulation for 60 minutes therapy.

Also known as: CES, Alpha-Stim™

True CES therapy; True CES therapy for non-responders

Sham Cranial electrical/electrotherapy stimulation (CES) DEVICE

Sham research units will be locked into active sham mode which provides stimulation designed to provide the sensation of stimulation for only 5 minutes while continuing to count down for the remaining 55 minutes.

Sham CES therapy

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be male and female age 40-80 years old
• Meet criteria for GWVI based on the CDC and Kansas Criteria for GWVI.
• CDC: 1 or more from at least 2 of the following categories for ≥ 6 months): 1) fatigue 2) mood and cognition (symptoms of feeling depressed, difficulty in remembering or concentrating, feeling moody, feeling anxious, trouble in finding words, or difficulty in sleeping) 3) musculoskeletal (symptoms of joint pain, joint stiffness, or muscle pain
• Subjects must self-report consistent, daily pain (greater than or equal to 4 on the DVPRS) \>90 days (prior to enrollment)
• Subjects must have intact skin free of infection at the site of electrode placement (earlobe).
• Subjects must be willing to participate and understand the consent.
• Subjects must be right-handed to provide consistency in brain structure and function.

You may not qualify if:

• Subjects must not be currently pregnant since effects of fMRI and electrical current on the developing fetus are not well-known.
• Subjects must not have a history of drug abuse or severe, uncontrolled psychiatric illness such as schizophrenia or major depressive disorder with suicidal ideation.
• Subjects must not have psoriasis vulgaris or other skin conditions that may increase the risk of infection at the implantation site.
• Subjects must not introduce new medications or treatments for symptoms during the study to prevent confounding results.
• Subjects must not have severe anxiety, claustrophobia, or other conditions that may prevent their ability to lie at rest in an MRI scanner. This will be determined after discussion with the patient regarding their own perceived ability to lie at rest in an MRI scanner without the use of additional sedating medications.
• Subjects must not have an implanted electrical device such as a surgically placed vagal stimulator, pacemaker, or spinal pain pump, which are not compatible with MRI.
• Subjects must not have a history of seizures or neurologic conditions that may alter the structure of the brain.
• Subjects must not be allergic to the metals used in electrodes for CES stimulation.
• Subjects must not have a diagnosed autoimmune disease that better explains pain symptoms.

Sponsors & Collaborators

• Emory University: lead
• Congressionally Directed Medical Research Programs: collaborator

Study Sites (1)

Emory Clinic

Atlanta, Georgia, 30307, United States

RECRUITING

MeSH Terms

Conditions

Persian Gulf Syndrome; Pain

Condition Hierarchy (Ancestors)

Occupational Diseases; War-Related Injuries; Wounds and Injuries; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Anna Woodbury, MD, MSc

  Emory University 404-727-8463

  PRINCIPAL INVESTIGATOR

• Lisa C Krishnamurthy, PhD

  Emory University 404-712-5332

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katherine Egan, RN, CCRC

CONTACT

404-727-8463; kfegan@emory.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: randomized, double-blind, sham-controlled clinical trial

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: September 3, 2025
• Study Start: September 26, 2025
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: September 1, 2030-September 1, 2032
• Access Criteria: \- Data will be shared including with: DOD ENIGMA Chronic Pain Working Group Device manufacturer for the CES in case they would like to apply for an FDA indication \- For the following type of analyses: Neuroimaging analysis Analysis of clinical outcomes \- Through a data usage agreement

Locations

US (1)