Vagus Nerve Stimulation: Treatment for Gulf Veterans With Gulf War Illness

The Three Phases of the Study

Subject Identification Phase of Study face to face visit at the War Related Illness & Injury
Study Center at the East Orange Veterans Administration Medical Center (EOVAMC).

Blinded Phase of Study Office Visit [first time at Icahn School of Medicine at Mount Sinai.
(ISMMS)] Subjects randomized to either VNS device or inactive device.

Open Label Phase of Study All subjects receive the VNS device

Inclusion Criteria:

To be eligible for enrollment in the Study, patients must meet all of the following
criteria:

- Patient is a veteran of the 1990-91 Gulf War, aged at least 42 years old

- Patient fulfills Kansas criteria for Gulf War Illness including endorsement of
musculoskeletal pain at moderate or severe intensities. This means patient has
endorsed symptoms in at least 3 of the following problem areas: Fatigue/sleep;
musculoskeletal pain; cognitive and mood; Gastrointestinal; respiratory; skin.

- Patient has widespread pain as evidenced by endorsement of pain in at least 3 bodily
quadrants plus in the axial skeleton

- Patient has a median 24 hour widespread pain score of at least 5 on a 0 to 10 VAS with
data taken on five days

- To be considered as having migraine, the patient must fulfill International Headache
Society (IHS) criteria, and it should have been present for at least one year prior to
entry into the study

- Patient agrees to use the study device as intended, follow all of the requirements of
the study including completion of diary after each self-treatment, follow-up visit
requirements, complete self assessment questionnaires as scheduled, and report any
adverse device effects to the study center within 24 hours of such adverse device
effect.

- Patient is able to provide written Informed Consent.

Exclusion Criteria:

Patients with any of the following will not be eligible for enrollment:

- Patient has a history of intracranial aneurysm, intracranial hemorrhage, brain tumor
or significant head trauma.

- Patient has in the opinion of the investigator a clinically relevant structural
abnormality at the gammaCore-R treatment site (e.g., neoplasm, lymphadenopathy,
previous surgery, neoplasm or abnormal anatomy).

- Patient has pain at the gammaCore treatment site (eg, dysesthesia, neuralgia,
cervicalgia).

- Patient has other significant pain problem (e.g., cancer pain or other head or facial
pain disorder) that in the opinion of the investigator may confound the study
assessments.

- Patient has known or suspected severe cardiac disease (e.g., symptomatic coronary
artery disease, prior myocardial infarction, congestive heart failure (CHF),
significant premature ventricular contraction) or a history of cardiac arrhythmia.

- Patient has known or suspected cerebrovascular disease (e.g., prior stroke or
transient ischemic attack, symptomatic carotid artery disease, prior carotid
endarterectomy or other vascular neck surgery).

- Patient's electrocardiogram shows evidence of heart disease or arrhythmia including an
abnormal baseline ECG (e.g. second and third degree heart block, prolonged QT interval
(corrected QT (QTcB) interval >470 msec for women and > 450 for men), atrial
fibrillation, atrial flutter, history of ventricular tachycardia or ventricular
fibrillation, or clinically significant premature ventricular contraction) or a
history of cardiac arrhythmia.

- Patient has had a previous cervical vagotomy.

- Patient has uncontrolled high blood pressure (systolic bp >160, or diastolic bp > 100)
after 3 measurements within 24 hours.

- Patient is currently implanted with an electrical and/or neurostimulator device (e.g.
cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator,
spinal stimulator, bone growth stimulator, or cochlear implant, Sphenopalatine
ganglion stimulator or Occipital nerve stimulator).

- Patient has been implanted with metal cervical spine hardware or has a metallic
implant near the gammaCore-R stimulation site.

- Patient has a history of significant syncope within the last 5 years.

- Patient has a history of non-epileptic or epileptic seizures within the last 5 years.

- Patient, in the opinion of the investigator, has a known history or suspicion of
substance abuse or addiction within the last 5 years.

- Patient, in the opinion of the investigator/research staff, the patient is incapable
of operating the gammaCore-R device as intended and performing the data collection
procedures.

- Patient has a psychiatric or cognitive disorder and/or behavioral problem which in the
opinion of the clinician may interfere with the study (e.g. Bipolar Disorder,
depressive disorder with psychotic features, Specific Phobia, Acute Stress Disorder).

- Patient is pregnant or thinking of becoming pregnant in the next 6 months, or is of
childbearing years and unwilling to use an accepted form of birth control or is
unwilling to undergo pregnancy testing.

- Patient is nursing

- Patient has undergone botulinum toxin (BOTOX) injections of the head and/or neck in
the last 3 months.

- Patient is participating or has participated in any other therapeutic clinical
investigation during the last 30 days.

- Patient belongs to a vulnerable population or has any condition such that his or her
ability to provide informed consent, comply with follow-up requirements, or provide
self-assessments is compromised (e.g., homeless, developmentally disabled, prisoner).

- Patient has evidence of suicidality based on the Columbia Suicide Screening test

- Patient has previously used a gammaCore device.

- Patient is the spouse or housemate of someone else in the trial.