Vagus Nerve Stimulation: Treatment for Gulf Veterans With Gulf War Illness
Vagus Nerve Stimulation: Treatment for Gulf Veterans With Gulf War Illness
The researchers propose studying Gulf veterans with Gulf War Illness (GWI), characterized by
 a problem with widespread pain. Besides their pain, the researchers will also assess the
 effect of vagus nerve stimulation (VNS) in alleviating migraine headache, another complaint
 of Gulf veterans, which is common in the presence of widespread pain. Importantly, the
 researchers are partnering with a company that has made a hand-held device that allows for
 stimulation of the vagus nerve without the need for surgery; it works by the patient putting
 it on the skin overlying the vagus nerve in their neck and then turning it on for 120 second
 periods three times a day. The device is programmed to deliver only 6 bouts of stimulation
 per day - one to each side of the neck three times a day; it is then inactive until the next
 day. The fact that this device can be used without surgery and is non-invasive makes it
 extremely practical for use.

 After collecting pre-treatment measurement of pain severity and headache severity, veterans
 will receive either the actual active VNS device or an inactive device, which does not
 stimulate the nerve. Veterans will use their device for ten weeks - providing similar
 information periodically over this period by responding to questions about the severity of
 their pain and headaches, They will then return to the Center for the final phase of the
 study where all veterans will receive active devices. Ten weeks later, they will return to
 the Center to provide information to allow the investigators to gain further knowledge as to
 the effectiveness of actual VNS in relieving pain - both throughout the body and in the head.
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.