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NCT02791893

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

Completed NA Results posted Last updated 3 May 2021
What this trial tests

NA trial testing VNS device in Pain in 27 participants. Completed in 15 April 2020.

Timeline
21 March 2017
Primary endpoint
15 April 2020
15 April 2020

Quick facts

Lead sponsorBenjamin Natelson
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment27
Start date21 March 2017
Primary completion15 April 2020
Estimated completion15 April 2020
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Benjamin Natelson

Who can join

Adults 42 to 80, any sex, with Pain or Migraine. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Visual Analog Scale (VAS) to Assess Change of Widespread Pain Primary · 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.

10 weeks
GroupValue95% CI
VNS Device4.70± 2.41
Inactive Device5.40± 2.27
20 weeks
GroupValue95% CI
VNS Device5.43± 2.07
Inactive Device3.56± 1.40
Patient Global Improvement of Change (PGIC) Secondary · 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.

10 weeks
GroupValue95% CI
VNS Device4.00± 2.06
Inactive Device3.11± 1.90
20 weeks
GroupValue95% CI
VNS Device3.71± 1.98
Inactive Device5.37± 1.41
Physical Function Subscale From the Short Form Health Survey (SF-36) Secondary · 10 and 20 weeks

A normalized indicator of physical functioning with a range from 0-100. Higher scores indicate fewer limitations to activity.

10 weeks
GroupValue95% CI
VNS Device65.50± 19.78
Inactive Device55.56± 24.81
20 weeks
GroupValue95% CI
VNS Device60.71± 32.97
Inactive Device56.25± 27.35
Number of Headache Days Collected From the Migraine Disability Assessment (MIDAS). Secondary · 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.

10 weeks
GroupValue95% CI
VNS Device4.10± 6.76
Inactive Device13.78± 23.49
20 weeks
GroupValue95% CI
VNS Device6.29± 10.63
Inactive Device14.25± 25.58
Depression Subscale From the Hospital Anxiety and Depression Scale (HADS) Secondary · 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.

10 weeks
GroupValue95% CI
VNS Device9.00± 2.26
Inactive Device10.11± 1.05
20 weeks
GroupValue95% CI
VNS Device7.50± 1.05
Inactive Device9.75± 2.25
Visual Analog Scale (VAS) to Assess Change of Widespread Pain Primary · 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.

Baseline
GroupValue95% CI
VNS Device6.18± 0.82
20 weeks
GroupValue95% CI
VNS Device4.43± 1.94

Adverse events — posted to ClinicalTrials.gov

Time frame: Patients were asked to provide reports on adverse events after the first week of the blinded phase (Week 1), at the end of the blinded phase (Week 11), and in the final week of the open label phase (Week 20). Adverse event monitoring for the sample took place over the course of 3 years (March, 2017 - March 2020).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

VNS Device
Serious: 1/13 (8%)
Deaths: 0/13
Inactive Device
Serious: 0/14 (0%)
Deaths: 0/14

Serious adverse events (1 terms)

ReactionSystemVNS DeviceInactive Device
Chest pains occurred shortly after randomizationGeneral disorders
Other adverse events (18 terms — click to expand)

ReactionSystemVNS DeviceInactive Device
HeadacheGeneral disorders
Metallic tasteGeneral disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Muscle tightnessGeneral disorders
Redness/irritationSkin and subcutaneous tissue disorders
Tingling sensationGeneral disorders
Lip droop/quiverMusculoskeletal and connective tissue disorders
Pain/radiating painGeneral disorders
TendernessGeneral disorders
ArrhythmiaCardiac disorders
Burning/stinging sensationGeneral disorders
DizzinessGeneral disorders
Facial droopsMusculoskeletal and connective tissue disorders
Frequent stoolsGastrointestinal disorders
LightheadednessGeneral disorders
NumbnessGeneral disorders
Small bumpsSkin and subcutaneous tissue disorders
SwellingGeneral disorders

Most-reported serious reactions: Chest pains occurred shortly after randomization.

Data from ClinicalTrials.gov NCT02791893 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Gulf War Illness: Mechanisms Underlying Brain Dysfunction and Promising Therapeutic Strategies.
    Dickey B, Madhu LN, Shetty AK. · · 2021 · cited 54× · PMID 33164782 · DOI 10.1016/j.pharmthera.2020.107716

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