A Pivotal Randomized Study Assessing VNS During Rehabilitation
Research type
Research Study
Full title
A Pivotal Randomized Study Assessing Vagus Nerve Stimulation (VNS) During Rehabilitation for Improved Upper Limb Motor Function After Stroke (VNS-REHAB)
IRAS ID
228128
Contact name
W Brent Tarver
Contact email
Sponsor organisation
MicroTransponder, Inc.
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 11 months, 31 days
Research summary
Summary of Research
This study will be randomised, controlled and participant, assessor and therapist blinded. There will be approximately 60 participants per study group (120 total study patients; only about 15 per study group in the UK or about 30 total in the UK). We will include participants who have suffered an ischaemic stroke between nine (9) months and ten (10) years prior to enrollment and who have disability due to arm weakness. All subjects who complete baseline assessments will be implanted with the Vivistim System. Participants will be randomised to one of two treatment groups; the first group will receive intensive rehabilitation therapy (control) and the second will receive vagal nerve stimulation (VNS, investigational treatment) during their intensive rehabilitation therapy . VNS involves implantation of a device (similar to a cardiac pacemaker but that stimulates the vagus nerve in the neck rather than the heart). Stimulation of the vagus nerve may cause release of important chemicals in the brain which help the brain recover after stroke. The purpose of the study is to determine the efficacy and safety of this therapy (VNS + Rehabilitation). It is the intent that this study support a PMA application to the US FDA. Participants will be followed for blinded assessment of outcomes for 90 days. Longer-term follow-up will continue while the device is implanted.NOTE: Control subjects will receive VNS during rehabilitation after the randomized portion of the study (after V7, 90 days after the end of randomised therapy).
Summary of Results
Long-term loss of arm function after ischaemic stroke is common. Some studies suggest that stimulating the nervous system during physical therapy sessions may make therapy more effective. In this study we assessed whether a type of stimulation called vagus nerve stimulation improved measures of arm movement and function in people whose arms had not recovered well after stroke.In the study, people from 19 stroke rehabilitation services in the UK and the USA, with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke were included. Participants were randomly assigned to receive either rehabilitation paired with active vagus nerve stimulation (VNS group), or rehabilitation paired with sham stimulation (control group). Everyone in the study had a device inserted and people who did not get active stimulation originally were allowed to receive it at the end of the study. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme where they did 30 minutes of exercises each day for 90 days. The main outcome measure in the study was the Fugl-Meyer upper extremity (FMA-UE) score which measures movement in the arm. An improvement of 6 points is felt to signify an important and clinically meaningful response.
The study involved 108 participants included between Oct 2, 2017, and Sept 12, 2019. 53 were in the VNS group and 55 in the control group. After completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points in the VNS group and by 2·4 points in the control group. After the period of home exercises, a clinically meaningful response was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group. There was one serious adverse event related to surgery (vocal cord paresis) in the control group.
In summary, Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm weakness after ischaemic stroke. It doubled the number of people who had a good outcome.
REC name
West of Scotland REC 4
REC reference
17/WS/0137
Date of REC Opinion
3 Aug 2017
REC opinion
Further Information Favourable Opinion