ReActiv8 Implantable Neurostimulation System for Chronic Low Back Pain

NCT02577354 | Completed Results DMC

• 1 other identifier: 950057
• Study Type: interventional
• Target: 204
• Locations: 5 countries
• Sites: 26

Brief Summary

The purpose of this trial is to evaluate the safety and efficacy of ReActiv8 for the treatment of adults with Chronic Low Back Pain when used in conjunction with medical management.

Conditions

Chronic Low Back Pain

Outcome Measures

Primary Outcomes (4)

• Responder Rate of Low Back Pain With No Increase in Pain Medications

  Comparison of responder rates for low back pain VAS between Treatment and Control groups. The Primary Efficacy Endpoint is a comparison of responder rates between Treatment and Control groups, where a "responder" is a participant with ≥30% reduction from baseline in average low back pain VAS, without any increase from baseline in pain medications and/or muscle relaxants for any reason including non low back pain reasons. The instrument used for evaluating pain is the continuous Visual Analog Scale (VAS) comprised of a horizontal line 10 cm in length, anchored by 2 verbal descriptors, where zero indicates no pain and 10 indicates worst imaginable pain. The value reported is a 7-day average low back pain. Any increase in dosage of a pain medication or any new pain medication taken for any reason counts as an increase in medications.

  120 Days

• Mean Change in Low Back Pain VAS

  Comparison of change in LBP VAS (120 days from baseline) between the Treatment and Control groups. The instrument used for evaluating pain is the continuous Visual Analog Scale (VAS) comprised of a horizontal line 10 cm in length, anchored by 2 verbal descriptors, where zero indicates no pain and 10 indicates worst imaginable pain. The value reported is a 7-day average low back pain. A change to a lower score (negative value) indicates improvement.

  120 Days

• Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels

  The CPRA, which was prespecified in the clinical protocol and statistical analysis plan prior to the start of the trial, was performed using the same data as used for the primary endpoint analysis and was included as part of the primary endpoint analysis

  120 Days

• Serious Device and/or Procedure Related Adverse Event Rate

  The primary safety assessment is of serious device and/or procedure related adverse events in all participants at 120 days. The 8 events reported below are 6 implant site pocket infections, 1 intra-operative upper airway obstruction, and 1 non-radicular, focal numbness on the surface of the thigh.

  120 Days

Secondary Outcomes (12)

• Change in Oswestry Disability Index (ODI)

  120 Days

• Change in European Quality of Life Score on Five Dimensions (EQ-5D)

  120 Days

• Change in Percent Pain Relief (PPR)

  120 Days

• Subject Global Impression of Change (SGIC)

  120 Days

• Resolution of Back Pain (VAS ≤2.5 cm)

  120 Days

Other Outcomes (6)

• Supplementary Analysis of Primary Endpoint: Responder Rate of Low Back Pain With No Increase in Low Back Pain Medications

  120 Days

• Treatment Satisfaction

  120 Days

• Treatment Satisfaction at One Year

  1 Year

Study Arms (2)

Treatment

EXPERIMENTAL

Device: ReActiv8 Implantable Stimulation System (Patient Appropriate Stimulation)

Control

EXPERIMENTAL

Device: ReActiv8 Implantable Stimulation System (Low Stimulation)

Interventions

ReActiv8 Implantable Stimulation System (Patient Appropriate Stimulation) DEVICE

ReActiv8 implanted and configured to deliver stimulation at a patient-appropriate level, and participants instructed to deliver stimulation in two 30-minute sessions per day.

Treatment

ReActiv8 Implantable Stimulation System (Low Stimulation) DEVICE

ReActiv8 implanted and configured to deliver low stimulation, and participants instructed to deliver stimulation in two 30-minute sessions per day.

Control

Eligibility Criteria

• Age: 22 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥22 years, ≤75 years
• Chronic Low Back Pain that has persisted \>90 days prior to the baseline visit.
• Continuing low back pain despite \>90 days of medical management.
• Qualifying pain score.
• Qualifying disability score.
• Evidence of lumbar multifidus muscle dysfunction.
• Be willing and capable of giving Informed Consent.
• Ability to comply with the instructions for use and to operate ReActiv8, and to comply with this Clinical Investigation Plan.

You may not qualify if:

• BMI \> 35
• Back Pain characteristics:
• Any surgical correction procedure for scoliosis at any time, or a current clinical diagnosis of scoliosis.
• Lumbar spine stenosis, as defined by an anterior-posterior diameter of the spinal canal of \<10mm in subjects with lower extremity pain.
• Neurological deficit possibly associated with the back pain (e.g. foot drop).
• Back pain due to pelvic or visceral reasons (e.g.: endometriosis or fibroids) or infection (e.g.: post herpetic neuralgia).
• Back pain due to inflammation or damage to the spinal cord or adjacent structures (e.g. arachnoiditis or syringomyelia).
• Pathology seen on MRI that is clearly identified and is likely the cause of the CLBP that is amenable to surgery.
• Back pain due to vascular causes such as aortic aneurysm and dissection.
• Any current indication for back surgery according to local institutional guidelines, or has indication for back surgery but cannot undergo surgery for other reasons.
• Leg pain described as being worse than back pain, or radiculopathy (neuropathic pain) below the knee.
• Source of pain is the sacroiliac joint as determined by the Investigator.
• Drug use.
• Any prior diagnosis of lumbar vertebral compression fracture, lumbar pars fracture, or lumbar annular tear with disc protrusion that is amenable to surgery.
• Planned surgery.

Sponsors & Collaborators

• Mainstay Medical: lead

Study Sites (26)

University of California, San Diego

La Jolla, California, United States

Location

The Spine Institute

Santa Monica, California, United States

Location

University of Colorado Hospital

Aurora, Colorado, United States

Location

Indiana Spine Group

Carmel, Indiana, United States

Location

OrthoIndy

Indianapolis, Indiana, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, United States

Location

The Brigham and Women's Hospital

Boston, Massachusetts, United States

Location

Beaumont Health

Royal Oak, Michigan, United States

Location

Duke University Medical Center

Durham, North Carolina, United States

Location

Center for Clinical Research

Winston-Salem, North Carolina, United States

Location

Louis Stokes VA Medical Center

Cleveland, Ohio, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Location

Rhode Island Hospital

Providence, Rhode Island, United States

Location

Upstate Clinical Trials

Spartanburg, South Carolina, United States

Location

Northwest Orthopaedic Specialists

Spokane, Washington, United States

Location

Center for Pain Relief

Charleston, West Virginia, United States

Location

Genesis Research Services

Broadmeadow, New South Wales, Australia

Location

Sunshine Coast Clinical Research

Noosa, Queensland, Australia

Location

Pain Medicine of South Australia

Welland, South Australia, Australia

Location

Monash Clinical Research

Clayton, Victoria, Australia

Location

AZ Nikolaas

Sint-Niklaas, Belgium

Location

Sint Augustinus

Wilrijk, Belgium

Location

Erasmus MC University Medical Center

Rotterdam, Netherlands

Location

Seacroft Hospital

Leeds, United Kingdom

Location

St. Bartholomew's Hospital

London, United Kingdom

Location

The James Cook University Hospital

Middlesbrough, United Kingdom

Location

Related Publications (6)

• Gilligan C, Burnside D, Grant L, Yong RJ, Mullins PM, Schwab F, Mekhail N. ReActiv8 Stimulation Therapy vs. Optimal Medical Management: A Randomized Controlled Trial for the Treatment of Intractable Mechanical Chronic Low Back Pain (RESTORE Trial Protocol). Pain Ther. 2023 Apr;12(2):607-620. doi: 10.1007/s40122-023-00475-4. Epub 2023 Feb 14.

  PMID: 36787013 BACKGROUND

• Gilligan C, Volschenk W, Russo M, Green M, Gilmore C, Mehta V, Deckers K, De Smedt K, Latif U, Georgius P, Gentile J, Mitchell B, Langhorst M, Huygen F, Baranidharan G, Patel V, Mironer E, Ross E, Carayannopoulos A, Hayek S, Gulve A, Van Buyten JP, Tohmeh A, Fischgrund J, Lad S, Ahadian F, Deer T, Klemme W, Rauck R, Rathmell J, Levy R, Heemels JP, Eldabe S; ReActiv8-B investigators. An implantable restorative-neurostimulator for refractory mechanical chronic low back pain: a randomized sham-controlled clinical trial. Pain. 2021 Oct 1;162(10):2486-2498. doi: 10.1097/j.pain.0000000000002258.

  PMID: 34534176 RESULT

• Gilligan C, Volschenk W, Russo M, Green M, Gilmore C, Mehta V, Deckers K, De Smedt K, Latif U, Georgius P, Gentile J, Mitchell B, Langhorst M, Huygen F, Baranidharan G, Patel V, Mironer E, Ross E, Carayannopoulos A, Hayek S, Gulve A, Van Buyten JP, Tohmeh A, Fischgrund J, Lad S, Ahadian F, Deer T, Klemme W, Rauck R, Rathmell J, Maislin G, Heemels JP, Eldabe S; ReActiv8-B Investigators. Long-Term Outcomes of Restorative Neurostimulation in Patients With Refractory Chronic Low Back Pain Secondary to Multifidus Dysfunction: Two-Year Results of the ReActiv8-B Pivotal Trial. Neuromodulation. 2023 Jan;26(1):87-97. doi: 10.1016/j.neurom.2021.10.011. Epub 2021 Dec 18.

  PMID: 35088722 RESULT

• Gilligan C, Volschenk W, Russo M, Green M, Gilmore C, Mehta V, Deckers K, De Smedt K, Latif U, Sayed D, Georgius P, Gentile J, Mitchell B, Langhorst M, Huygen F, Baranidharan G, Patel V, Mironer E, Ross E, Carayannopoulos A, Hayek S, Gulve A, Van Buyten JP, Tohmeh A, Fischgrund J, Lad S, Ahadian F, Deer T, Klemme W, Rauck R, Rathmell J, Schwab F, Maislin G, Heemels JP, Eldabe S. Three-Year Durability of Restorative Neurostimulation Effectiveness in Patients With Chronic Low Back Pain and Multifidus Muscle Dysfunction. Neuromodulation. 2023 Jan;26(1):98-108. doi: 10.1016/j.neurom.2022.08.457. Epub 2022 Sep 27.

  PMID: 36175320 RESULT

• Gilligan C, Volschenk W, Russo M, Green M, Gilmore C, Mehta V, Deckers K, De Smedt K, Latif U, Sayed D, Georgius P, Gentile J, Mitchell B, Langhorst M, Huygen F, Baranidharan G, Patel V, Mironer E, Ross E, Carayannopoulos A, Hayek S, Gulve A, Van Buyten JP, Tohmeh A, Fischgrund J, Lad S, Ahadian F, Deer T, Klemme W, Rauck R, Rathmell J, Maislin G, Heemels JP, Eldabe S. Five-Year Longitudinal Follow-Up of Restorative Neurostimulation Shows Durability of Effectiveness in Patients With Refractory Chronic Low Back Pain Associated With Multifidus Muscle Dysfunction. Neuromodulation. 2024 Jul;27(5):930-943. doi: 10.1016/j.neurom.2024.01.006. Epub 2024 Mar 12.

  PMID: 38483366 RESULT

• Shaffrey C, Gilligan C. Effect of Restorative Neurostimulation on Major Drivers of Chronic Low Back Pain Economic Impact. Neurosurgery. 2023 Apr 1;92(4):716-724. doi: 10.1227/neu.0000000000002305. Epub 2023 Feb 14.

  PMID: 36786565 DERIVED

Limitations and Caveats

Dichotomization of primary endpoint reduced statistical power by losing information on exact response magnitude. This limitation is addressed by the cumulative proportion of responders analysis of the primary endpoint data (Outcome Measure #3).

Results Point of Contact

• Title: Vice President Clinical Affairs
• Organization: Mainstay Medical

diane.burnside@mainstay-medical.com

7637727637

Study Officials

• Chris Gilligan, MD, MBA

  Brigham and Women's Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 16, 2015
• Study Start: August 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: January 1, 2024
• Last Updated: February 27, 2025
• Results First Posted: October 19, 2020

Record last verified: 2025-02

Locations

GB (3); AU (4); BE (2); US (16); NL (1)