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

• ClinicalTrials.gov Identifier: NCT02791893
• Recruitment Status: Completed
• First Posted: June 7, 2016
• Results First Posted: May 3, 2021
• Last Update Posted: May 3, 2021
• Sponsor: Benjamin Natelson
• Information provided by (Responsible Party): Benjamin Natelson, Icahn School of Medicine at Mount Sinai

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pain; Migraine	Device: VNS device; Device: Inactive device	Not Applicable

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Vagus Nerve Stimulation: A Non-invasive Treatment to Improve the Health of Gulf Veterans With Gulf War Illness
• Actual Study Start Date: March 21, 2017
• Actual Primary Completion Date: April 15, 2020
• Actual Study Completion Date: April 15, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: VNS device; Vagus Nerve Stimulation (VNS) hand held device - subjects to utilize the VNS hand held device for 20 weeks total, 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	Device: VNS device; Hand held device to use for self administration of vagus nerve stimulation.; Other Name: Non-InvasiveVagus Nerve Stimulation (nVNS) Therapy
Placebo Comparator: Inactive device; Inactive hand held device - subjects to utilize the inactive device for 10 weeks and then will receive the VNS device for the next 10 weeks.	Device: VNS device; Hand held device to use for self administration of vagus nerve stimulation.; Other Name: Non-InvasiveVagus Nerve Stimulation (nVNS) Therapy; Device: Inactive device; Hand held device to use for self administration of simulated vagus nerve stimulation.

Outcome Measures

Primary Outcome Measures :

1. Visual Analog Scale (VAS) to Assess Change of Widespread Pain [ Time Frame: 10 and 20 weeks ]
   Patients used the Pain Visual Analog Scale (0-10; 0=No pain, 10=Worst pain possible) to rate their average level of pain over the last 24 hours. The median value for each individual's ratings over 5 consecutive days immediately prior to the end of the intervention period was recorded and then the average was calculated for each group.
2. Visual Analog Scale (VAS) to Assess Change of Widespread Pain [ Time Frame: Baseline and 20 weeks ]
   Patients used the Pain Visual Analog Scale (0-10; 0=No pain, 10=Worst pain possible) to rate their average level of pain over the last 24 hours. The median value for each individual's ratings over 5 consecutive days immediately prior to the end of the intervention period was recorded and then the average was calculated for each group.

Secondary Outcome Measures :

1. Patient Global Improvement of Change (PGIC) [ Time Frame: 10 and 20 weeks ]
   PGIC is a 7-point scale used to quantify a patient's rating of overall improvement. Patients rate their change from 1 (no change or gotten worse) to 7 (considerable improvement). Higher scores indicate greater improvement since starting the intervention.
2. Physical Function Subscale From the Short Form Health Survey (SF-36) [ Time Frame: 10 and 20 weeks ]
   A normalized indicator of physical functioning with a range from 0-100. Higher scores indicate fewer limitations to activity.
3. Number of Headache Days Collected From the Migraine Disability Assessment (MIDAS). [ Time Frame: 10 and 20 weeks ]
   Participants are asked to indicate the number of days in the last 3 months during which they experienced a headache. If a headache lasted more than 1 day, they are instructed to count each day. Scores are expected between 0-90 with higher numbers corresponding to a greater number of headache days.
4. Depression Subscale From the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 10 and 20 weeks ]
   The HADS is a 14-item scale intended to quantify symptoms of depression and anxiety. Scores range from 0-21 on each subscale (Anxiety and Depression) with higher scores indicating a greater number of symptoms.

Eligibility Criteria

• Ages Eligible for Study: 42 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 visual analog scale (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.

Contacts and Locations

Locations

United States, New Jersey

East Orange Veterans Administration Medical Center

East Orange, New Jersey, United States, 07018

United States, New York

Mount Sinai Beth Israel

New York, New York, United States, 10003

Pain and Fatigue Study Center - Beth Israel Medical Center

New York, New York, United States, 10014

Pain and Fatigue Study Center - Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

Sponsors and Collaborators

Benjamin Natelson

Investigators

• Study Director: Benjamin H Natelson, MD; Icahn School of Medicine at Mount Sinai

  Study Documents (Full-Text)

Documents provided by Benjamin Natelson, Icahn School of Medicine at Mount Sinai:

Study Protocol and Statistical Analysis Plan  [PDF] July 15, 2019

Informed Consent Form  [PDF] August 29, 2019

More Information

• Responsible Party: Benjamin Natelson, Professor of Neurology, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT02791893
• Other Study ID Numbers: GCO 16-0350
• First Posted: June 7, 2016
• Results First Posted: May 3, 2021
• Last Update Posted: May 3, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes