PainNCT02791893
Vagus Nerve Stimulation: Treatment for Gulf Veterans With Gulf War Illness
A study testing VNS device and Inactive device in people with Pain and Migraine, run by Benjamin Natelson at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 42 to 80 years
- What is being tested?
- VNS device and Inactive device
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 4 sitesUnited States
- Study dates
- 21 Mar 2017to 15 Apr 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 42 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
East Orange Veterans Administration Medical Center
East Orange, New Jersey, 07018
Mount Sinai Beth Israel
New York, New York, 10003
Pain and Fatigue Study Center - Beth Israel Medical Center
New York, New York, 10014
Pain and Fatigue Study Center - Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Vagus Nerve Stimulation: A Non-invasive Treatment to Improve the Health of 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.
Read the 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
- Being tested
- VNS device, Inactive device
- Medical subject headings
- Pain, Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VNS deviceDevice
Also called Non-InvasiveVagus Nerve Stimulation (nVNS) Therapy
Hand held device to use for self administration of vagus nerve stimulation.
Inactive deviceDevice
Hand held device to use for self administration of simulated vagus nerve stimulation.
| Study group | Role | What they receive |
|---|---|---|
| VNS device | Experimental | 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 Receives: Device: VNS device |
| Inactive device | Placebo comparator | 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. Receives: Device: VNS device; Device: Inactive device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Analog Scale (VAS) to Assess Change of Widespread Pain
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.
Measured: 10 and 20 weeks
Visual Analog Scale (VAS) to Assess Change of Widespread Pain
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.
Measured: Baseline and 20 weeks
Secondary outcomes (4)
Patient Global Improvement of Change (PGIC)
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.
Measured: 10 and 20 weeks
Physical Function Subscale From the Short Form Health Survey (SF-36)
A normalized indicator of physical functioning with a range from 0-100. Higher scores indicate fewer limitations to activity.
Measured: 10 and 20 weeks
Number of Headache Days Collected From the Migraine Disability Assessment (MIDAS).
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.
Measured: 10 and 20 weeks
Depression Subscale From the Hospital Anxiety and Depression Scale (HADS)
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.
Measured: 10 and 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2016 (estimated)
- Study start21 Mar 2017
- Primary completion15 Apr 2020
- Study completion15 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Benjamin Natelson
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Benjamin Natelson, Icahn School of Medicine at Mount Sinai
- Investigators
- Benjamin H Natelson, MD, Study director, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02791893
- Sponsor's protocol ID
- GCO 16-0350
- Status last verified
- Apr 2021
- First submitted
- 30 May 2016
- Last updated
- 3 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vagus Nerve Stimulation: A Non-invasive Treatment to Improve the Health of Gulf Veterans With Gulf War Illness
- ClinicalTrials.gov ID
- NCT02791893
- Acronym / sponsor ID
- GCO 16-0350
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Benjamin NatelsonUniversity, hospital or other
- Study start
- 21 Mar 2017 (actual)
- Primary completion
- 15 Apr 2020 (actual)
- Study completion
- 15 Apr 2020 (actual)
- First posted
- 7 Jun 2016 (estimated)
- Results
- Posted 3 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VNS device | Experimental | Device: VNS deviceVagus 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 |
| Inactive device | Placebo comparator | Device: VNS device, Device: Inactive deviceInactive hand held device - subjects to utilize the inactive device for 10 weeks and then will receive the VNS device for the next 10 weeks. |
Who may qualify
- Ages
- 42 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VNS deviceAlso: Non-InvasiveVagus Nerve Stimulation (nVNS) TherapyHand held device to use for self administration of vagus nerve stimulation. | Device | Inactive device, VNS device |
| Inactive deviceHand held device to use for self administration of simulated vagus nerve stimulation. | Device | Inactive device |
Primary outcome
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.
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.
4 secondary outcomes
Patient Global Improvement of Change (PGIC)
Time frame: 10 and 20 weeks
Physical Function Subscale From the Short Form Health Survey (SF-36)
Time frame: 10 and 20 weeks
Number of Headache Days Collected From the Migraine Disability Assessment (MIDAS).
Time frame: 10 and 20 weeks
Depression Subscale From the Hospital Anxiety and Depression Scale (HADS)
Time frame: 10 and 20 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin H Natelson, MD study director
Icahn School of Medicine at Mount Sinai
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing VNS device and Inactive device in people with Pain and Migraine, run by Benjamin Natelson at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Analog Scale (VAS) to Assess Change of Widespread Pain (time frame: 10 and 20 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2021.