Cranial electrical stimulation with brain imaging for Gulf War illness headaches and pain

ELECTRIG: Evaluating Effects of Cranial Electrical Stimulation Therapy With Responsive Imaging in Gulf War Illness Pain and Comorbid Symptoms

This project will try a portable cranial electrical stimulation device (Alpha-Stim) to see if it reduces headaches and body pain in Gulf War veterans with Gulf War Illness.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 130 (estimated)
• Ages: 40 Years to 80 Years
• Sex: All
• Sponsor: Emory University (Academic / other)
• Locations: 1 site (Atlanta, Georgia)
• Trial ID: NCT07151248 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, sham-controlled adaptive trial will randomize 104 Gulf War veterans to active or sham cranial electrical stimulation (CES) to test symptom change. Participants will undergo brain imaging including MRI and magnetic resonance spectroscopy (MRS) to probe brain connectivity and possible neuroinflammation linked to headache and pain. The intervention uses an FDA‑cleared portable CES device (Alpha‑Stim) delivered repeatedly over the treatment period. Recruitment and clinical visits, including imaging, occur at Emory University clinics in Atlanta for adults aged 40–80 who meet CDC and Kansas criteria for Gulf War Illness.

Who should consider this trial

Good fit: Gulf War veterans aged 40–80 who meet CDC and Kansas criteria for Gulf War Illness and report consistent daily headache and pain are ideal candidates.

Not a fit: People who do not meet Gulf War Illness criteria, are outside the 40–80 age range, or have exclusionary conditions (including pregnancy, cognitive impairment, or other specified exclusions) are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, participants could experience reduced headaches and pain and gain access to a nonpharmacological, portable treatment option.

How similar studies have performed: Alpha‑Stim is FDA‑cleared for anxiety, insomnia, and pain and prior small studies have shown promising but limited results, while combining CES with advanced MRI/MRS in Gulf War Illness is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Subjects must be male and female age 40-80 years old
2. 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
   * Kansas: 3 of 6 domains: 1) fatigue and sleep problems 2) pain symptoms 3) neurologic, cognitive, or mood symptoms 4) gastrointestinal symptoms 5) respiratory symptoms 6) skin symptoms chronic since 1990. Symptom reporting must be in the absence of diagnosed exclusionary conditions; only respondents who have at least 1 moderately severe symptom or 2 or more symptoms within a group were considered to have a high level of symptoms in the group.
3. Subjects must self-report consistent, daily pain (greater than or equal to 4 on the DVPRS) \>90 days (prior to enrollment)
4. Subjects must have intact skin free of infection at the site of electrode placement (earlobe).
5. Subjects must be willing to participate and understand the consent.
6. Subjects must be right-handed to provide consistency in brain structure and function.

Exclusion Criteria:

1. Subjects must not be currently pregnant since effects of fMRI and electrical current on the developing fetus are not well-known.
2. Subjects must not have a history of drug abuse or severe, uncontrolled psychiatric illness such as schizophrenia or major depressive disorder with suicidal ideation.
3. Subjects must not have psoriasis vulgaris or other skin conditions that may increase the risk of infection at the implantation site.
4. Subjects must not introduce new medications or treatments for symptoms during the study to prevent confounding results.
5. 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.
6. 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.
7. Subjects must not have a history of seizures or neurologic conditions that may alter the structure of the brain.
8. Subjects must not be allergic to the metals used in electrodes for CES stimulation.
9. Subjects must not have a diagnosed autoimmune disease that better explains pain symptoms.

Where this trial is running

Atlanta, Georgia

• Emory Clinic — Atlanta, Georgia, United States (Recruiting)

Study contacts

• Principal investigator: Anna Woodbury, MD, MSc — Emory University 404-727-8463
• Study coordinator: Katherine Egan, RN, CCRC

Conditions Gulf War Syndrome; Gulf War Illness Headaches and Pain