Paired VNS™ Treatment uses Vagus Nerve Stimulation (VNS) Paired with Rehabilitation Exercises
The results of this clinical study were published in the American Heart Association journal Stroke in 2015. The full text of the paper can be read on the AHA website HERE.
We are currently recruiting for a large study in the U.S. and UK. www.vnsstroketrial.com
- - Multicenter (2 site) United Kingdom study
- - MHRA reviewed study of 20 patients assessing VNS paired with rehabilitation for improving upper-limb function in an ischemic stroke population.
The main objective of the study was to evaluate the safety and feasibility of the therapy, including the surgical intervention and stimulation, as well as to provide information on the appropriateness of the functional outcome measures, and to provide a basis for sample size calculations for larger studies.
Enrolled patients were at least 6 months post-stroke with upper-limb deficits.
Patients were randomized to one of two groups:
- 1) a group implanted with the Vivistim® device that enabled pairing of VNS with rehabilitation
- 2) a control group that received identical rehabilitation therapy (but no device implant).
Patients had baseline evaluations followed by six weeks of rehabilitation alone (control arm) or VNS + rehabilitation (therapy arm). Assessors were blinded to treatment group assignment.
During each in-clinic therapy session, the patient performed several Activities of Daily Living (ADL) based tasks.
A typical session lasted for approximately 90 minutes.
Each of the movements was task-specific, repetitive and intensive. Patients performed approximately 300-400 movement trials per session. For the VNS group, each movement trial was paired with a brief 0.5 second burst of VNS. The control group received the same number of movement trials; however, no VNS was delivered.
The mean age of subjects was 57.9 years, with the mean time since their stroke of 1.8 years. Both groups had a similar demographic composition.
The primary endpoint was safety and feasibility. The secondary endpoints included measures of upper-limb function using the Fugl-Meyer Assessment - Upper Extremity (FMA-UE) scale.
Subjects tolerated both the surgery and stimulation similarly to the commercially approved indications of VNS for epilepsy and depression.
There were no significant compliance issues and no serious adverse events related to therapy.
The increase in FMA-UE scores was significantly greater in the VNS treated group at the end of treatment compared to the control arm. (9.6 vs. 3.0, p=0.038) (Fig. 1)
Of the patients that received VNS paired therapy, 75% responded to the therapy (FMA-UE change greater than or equal to 6 points.) Only 36% of the control group were responders. (Fig. 2)
The patients in the study were treated an average of 1.8 years after their stroke. Traditional post-stroke recovery generally plateaus within the first six months after a stroke.
These results suggest that VNS appears effective and has not raised safety concerns in adults with chronic stroke (Dawson et al., 2015).
Key Inclusion & Exclusion Criteria
Key Inclusion Criteria
- -History of unilateral supratentorial ischemic stroke that occurred at least 6 months prior (no upper limit)
- -Age between 18 and 80 years
- -Right or left sided weakness of upper extremity
- -Action Research Arm Test (ARAT) score of 15 to 50 (inclusive of 15 and 50)
- -At least 5 degrees of active wrist extension
Key Exclusion Criteria
- -Hemorrhagic stroke
- -Any major neurological, psychiatric, or other deficits that would interfere with the study (including severe depression)
- -Taking any medication thought to interfere with VNS (such as centrally acting norepinephrine or acetylcholine blockers)
- -Active rehabilitation within 4 weeks of enrollment
- -Not a good surgical candidate
Demographics and Characteristics
|Variable||VNS + Rehabilitation||Rehabilitation Only|
|Age, years (mean (SD)||57-9 (17-2)||60.7 (10.7)|
|Male sex||7 (77-8%)||9 (81.8%)|
|Dominant Hand (right)||8 (88-9%)||10 (90.9%)|
|Time from stroke, years (mean (SD))||1-8 (1-0)||1.7 (1.3)|
|Duration of rehabilitation|
|0-3 months||0||5 (45.5%)|
|3-12 months||8 (88-9%)||6 (54.5%)|
|>12 months||1 (11-1%)||0|
|Paretic Limb (right)||3 (33-3%)||4 (36.4%)|
|Cortical Involvement||6 (66-7%)||3 (30.0%)|
|Fugl-Meyer Score (mean (SD))||40-1 (9-7)||45.3 (8.4)|
|ARAT Score (mean (SD))||32-6 (7-2)||34.0 (8.1)|
Baseline demographics in VNS treated and rehabilitation only participants. Values shown are n (%) unless otherwise shown.
The Vivistim® System was well tolerated with similar safety and adverse events as VNS treatment for epilepsy, which has now been implanted in over 100,000 patients worldwide over the past 21 years.
In general, adverse events were mild and resolved. This study showed that a therapy pairing VNS with rehabilitation exercises had a similar side effect and safety profile as VNS therapy for epilepsy and depression. A full discussion related to the safety of the Paired VNS™ stroke study can be found in the published article HERE.
Current Pilot Study
MicroTransponder is currently performing a U.S./U.K. randomized clinical trial on 20 patients
See www.vnsstroketrial.com to enroll and find more information.
The subjects in the currently ongoing U.S./UK Stroke trial are divided into 2 groups. All patients are being implanted with the Vivistim® System. One group is receiving VNS paired with rehabilitative exercises, while the “control” group is receiving VNS that is NOT paired with the rehabilitative exercises. The patients in both groups are participating in 90-120 minute sessions 3 times a week for a total of 6 weeks and then another 4 weeks of assessment follow-up. The “control” group will cross over after 18 weeks (the initial 10 week acute study and another 8 week washout period) and then begin therapy where the VNS is paired with their rehabilitative exercises. Moreover, at the conclusion of the controlled randomized portion of the study, patients are given specific exercises to perform at home and the ability to activate programmed VNS delivery during those exercises for continued improvements and maintenance of improvement.