Teresa Jacobson Kimberley, PhD, PT

Transcription

1 Teresa Jacobson Kimberley, PhD, PT Professor MGH Institute of Health Professions School of Rehabilitation and Health Sciences Department of Physical Therapy

2 Disclosures Human pilot trial in VNS and stroke being discussed was funded in whole by a research grant from MicroTransponder, Inc. the manufacturer of the Vivistim System. Previously I have received travel reimbursement to present the pilot trial results I have no other conflicts

3 Vagus Nerve

4 Vagus Nerve Key in regulation of metabolic homeostasis through its afferent and efferent pathways

5 Vagus Nerve Stimulation Is FDA approved for: refractory epilepsy (Left) Treatment resistant depression (Left) Small studies have shown some effectiveness: Heart failure (Right) Tinnitus (Left) Migraine (transcutaneous) Stroke (Left)

6 Ischemic stroke model VNS paired with sensory stimulation or motor practice Engineer et al., 2011, Porter et al., 2011

7 Paired Un-Paired Khodaparast et al, 2013 Ischemic stroke rat model Paired VNS improves recovery of hit rate performance and force on compared with Rehab alone and unpaired VNS

8 Rehabilitation VNS: potential mechanisms Neural Plasticity Rehab input + Vagal Nerve Stimulation NTS From: Carey et al, Brain. 2002;125(4): Locus Ceruleus Nucleus Basalis Neural Plasticity

9 VNS paired with rehabilitation first clinical study - 20 participant study - PROBE design - 11 non-implant Controls - 9 Implanted Active Therapy - ITT Analysis pt difference; 95% CI: -0.4, Per-Protocol Analysis pt difference; 95% CI; 0.4, Responder rate: - 75% VNS vs. 38% Controls - Feasible, moving forward justified page 9

10 Study II: A Randomized Double-Blind Pilot Study Assessing Vagus Nerve Stimulation (VNS) During Rehabilitation for Improved Upper Limb Motor Function After Stroke page 10

11 Design Population Intervention Comparator Double blind, randomized, controlled study Ischaemic stroke between 4 months and 5 years Mod mod/severe arm weakness (FMA 20 to 50) VNS + Rehabilitation, 6 weeks + home exercise for 90 days Sham VNS + Rehabilitation, 6 weeks + home exercise for 90 days Cross over to receive 6 weeks VNS thereafter Outcomes UEFM, WMFT performed at baseline, day 1 after 6 weeks therapy completion and at days 30, 90 thereafter Blinding Participant, therapists and assessors blinded out to day 90 after therapy completion

12 The VNS therapy VNS device implanted 6-weeks in-clinic VNS 0.5 second, 0.8mA stimulation given per movement (0.0 ma in controls) Approx. 400 stimulations per session Patients then undergo 30 minutes of VNS daily at home for long term

13 Upper extremity therapy Graded, progressive task practice ~300 repetitions Average 72 minutes 18 sessions (3x/week for 6 weeks)

14 22 participants assessed, consented, enrolled 17 Subjects Implanted and Randomized 3 investigator excluded (poor surgical candidates) 2 self exclusion (time and surgery concerns) 8 in VNS Group 9 in Control Group 8 Per Protocol VNS Group 8 Per Protocol Control Group 1 eligibility exclusion (poor sensory function) page 14

15 Results Safety data Three SAEs. All related to surgery, all in controls Infection [resolved] Shortness of breath and dysphagia - intubation [resolved] Vocal cord paralysis [improving but ongoing] Other AEs Typical surgical events (bruising, pain, swelling, scaring) No events definitely or likely related to stimulation No cardiac events page 15

16 Results - UEFM responder rates Response Defined as UEFM 6 points % 75% 38% 88% 88% 33% Controls VNS 0 End of Therapy Day 30 Day 90 p=0.15 p=0.11 p=0.05

17 In-clinic Therapy Upper extremity Fugl Meyer Paired VNS Control In-clinic Therapy n=4 12 P= UEFM Change UEFM Change Cross-over 2 Paired VNS 0 Base 6 weeks Post-30 3MO 0 Rebaseline 6 weeks Kimberley et al, in progress

18 Wolf motor function - performance

19 Summary Findings suggests there may be additional benefit to VNS pairing with rehabilitation. This pilot study confirms previous feasibility study results and larger studies are justified. A 120 participant pivotal study is underway in 15 sites Rehabilitation pairing appears to be a critical component