ReActiv8 Implantable Neurostimulation System for Chronic Low Back Pain (ReActiv8-B)

ReActiv8 Implantable Neurostimulation System for Chronic Low Back Pain (ReActiv8-B)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Low Back Pain
• Intervention / Treatment: Device: ReActiv8 Implantable Stimulation System (Patient Appropriate Stimulation); Device: ReActiv8 Implantable Stimulation System (Low Stimulation)

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Broadmeadow, New South Wales, Australia
      • Genesis Research Services
  • Queensland
    • Noosa Heads, Queensland, Australia
      • Sunshine Coast Clinical Research
  • South Australia
    • Welland, South Australia, Australia
      • Pain Medicine of South Australia
  • Victoria
    • Clayton, Victoria, Australia
      • Monash Clinical Research
• Belgium
  • Sint-Niklaas, Belgium
    • AZ Nikolaas
  • Wilrijk, Belgium
    • Sint Augustinus
• Netherlands
  • Rotterdam, Netherlands
    • Erasmus MC University Medical Center
• United Kingdom
  • Leeds, United Kingdom
    • Seacroft Hospital
  • London, United Kingdom
    • St. Bartholomew's Hospital
  • Middlesbrough, United Kingdom
    • The James Cook University Hospital
• United States
  • California
    • La Jolla, California, United States
      • University of California, San Diego
    • Santa Monica, California, United States
      • The Spine Institute
  • Colorado
    • Aurora, Colorado, United States
      • University of Colorado Hospital
  • Indiana
    • Carmel, Indiana, United States
      • Indiana Spine Group
    • Indianapolis, Indiana, United States
      • OrthoIndy
  • Kansas
    • Kansas City, Kansas, United States
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States
      • The Brigham and Women's Hospital
  • Michigan
    • Royal Oak, Michigan, United States
      • Beaumont Health
  • North Carolina
    • Durham, North Carolina, United States
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States
      • Center for Clinical Research
  • Ohio
    • Cleveland, Ohio, United States
      • Louis Stokes VA Medical Center
    • Cleveland, Ohio, United States
      • University Hospitals Cleveland Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States
      • Rhode Island Hospital
  • South Carolina
    • Spartanburg, South Carolina, United States
      • Upstate Clinical Trials
  • Washington
    • Spokane, Washington, United States
      • Northwest Orthopaedic Specialists
  • West Virginia
    • Charleston, West Virginia, United States
      • Center for Pain Relief

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥22 years, ≤75 years
2. Chronic Low Back Pain that has persisted >90 days prior to the baseline visit.
3. Continuing low back pain despite >90 days of medical management.
4. Qualifying pain score.
5. Qualifying disability score.
6. Evidence of lumbar multifidus muscle dysfunction.
7. Be willing and capable of giving Informed Consent.
8. Ability to comply with the instructions for use and to operate ReActiv8, and to comply with this Clinical Investigation Plan.
9. Suitable for ReActiv8 surgery as determined by the implanting physician prior to inclusion.

Exclusion Criteria:

1. BMI > 35

2. Back Pain characteristics:

   1. Any surgical correction procedure for scoliosis at any time, or a current clinical diagnosis of scoliosis.
   2. Lumbar spine stenosis, as defined by an anterior-posterior diameter of the spinal canal of <10mm in subjects with lower extremity pain.
   3. Neurological deficit possibly associated with the back pain (e.g. foot drop).
   4. Back pain due to pelvic or visceral reasons (e.g.: endometriosis or fibroids) or infection (e.g.: post herpetic neuralgia).
   5. Back pain due to inflammation or damage to the spinal cord or adjacent structures (e.g. arachnoiditis or syringomyelia).
   6. Pathology seen on MRI that is clearly identified and is likely the cause of the CLBP that is amenable to surgery.
   7. Back pain due to vascular causes such as aortic aneurysm and dissection.
3. Any current indication for back surgery according to local institutional guidelines, or has indication for back surgery but cannot undergo surgery for other reasons.
4. Leg pain described as being worse than back pain, or radiculopathy (neuropathic pain) below the knee.
5. Source of pain is the sacroiliac joint as determined by the Investigator.
6. Drug use.
7. Surgical and other procedures exclusions.
8. Any prior diagnosis of lumbar vertebral compression fracture, lumbar pars fracture, or lumbar annular tear with disc protrusion that is amenable to surgery.
9. Planned surgery.
10. Co-morbid chronic pain conditions.
11. Other clinical conditions.
12. Psycho-social exclusions.
13. Protocol compliance exclusions.
14. General exclusions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment	Device: ReActiv8 Implantable Stimulation System (Patient Appropriate Stimulation); 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.
Experimental: Control	Device: ReActiv8 Implantable Stimulation System (Low Stimulation); ReActiv8 implanted and configured to deliver low stimulation, and participants instructed to deliver stimulation in two 30-minute sessions per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Oswestry Disability Index (ODI)	Comparison of change in ODI (120 days from baseline) between Treatment and Control groups. ODI is reported as a score from 0 to 100%, where 0%-20% indicates minimal disability, 21%-40% indicates moderate disability, 41%-60% indicates severe disability, 61%-80% indicates crippled, and 81%-100% indicates bedbound or an exaggeration of symptoms. A change to a lower score (negative value) indicates improvement.	120 Days
Change in European Quality of Life Score on Five Dimensions (EQ-5D)	Comparison of change in EQ-5D (120 days from baseline) between Treatment and Control groups. The EQ-5D Index is scored on a scale of -0.594 to 1.00, with a score of 1.00 indicating full health. A change to a higher score (positive value) indicates improvement.	120 Days
Change in Percent Pain Relief (PPR)	PPR is a patient-reported percent of pain relief at 120 days compared to the pain at baseline, where 0% indicates no pain relief compared to baseline, and 100% indicates complete pain relief compared to baseline.	120 Days
Subject Global Impression of Change (SGIC)	A questionnaire completed with the following item: Since I enrolled in the study, my overall status is 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse	120 Days
Resolution of Back Pain (VAS ≤2.5 cm)	Resolution of back pain (remitter rate) was defined as a participant with 7-day average low back pain VAS ≤2.5 cm on the 10 cm VAS.	120 Days
LBP VAS Responder Rate at One Year	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. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.	1 Year
Mean Change in LBP VAS at One Year	Change in LBP VAS at 1 year compared to baseline. 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, one for each symptom extreme for Low Back Pain. Zero indicates no pain and 10 indicates worst imaginable pain. The value reported is a 7-day average low back pain. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. A change to a lower score (negative value) indicates improvement.	1 Year
Change in Oswestry Disability Index (ODI) at One Year	Change in ODI at 1 year compared to baseline. ODI is reported as a score from 0 to 100%, where 0%-20% indicates minimal disability, 21%-40% indicates moderate disability, 41%-60% indicates severe disability, 61%-80% indicates crippled, and 81%-100% indicates bedbound or an exaggeration of symptoms. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. A change to a lower score (negative value) indicates improvement.	1 Year
Change in European Quality of Life Score on Five Dimensions (EQ-5D) at One Year	Change in EQ-5D at 1 year compared to baseline. The EQ-5D Index is scored on a scale of -0.594 to 1.00, with a score of 1.00 indicating full health. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. A change to a higher score (positive value) indicates improvement.	1 Year
Percent Pain Relief at One Year	PPR is a patient-reported percent of pain relief compared to the pain at baseline, where 0% indicates no pain relief compared to baseline, and 100% indicates complete pain relief compared to baseline. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.	1 Year
Subject Global Impression of Change (SGIC) at One Year	A questionnaire with the following item: Since I enrolled in the study, my overall status is 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.	1 Year
Resolution of Back Pain at One Year	Resolution of back pain (remitter rate) was defined as a participant with 7-day average low back pain VAS ≤2.5 cm on the 10 cm VAS. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.	1 Year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Supplementary Analysis of Primary Endpoint: Responder Rate of Low Back Pain With No Increase in Low Back Pain Medications	This pre-specified analysis of the primary endpoint examines the impact of rescue medications taken for acute pain conditions for reasons other than low back pain, by excluding those participants from the analysis who took rescue medications for reasons other than low back pain. Nine participants in both groups increased pain medications. In the control group, all nine participants increased pain medications due to low back pain. In the treatment group, three of the nine participants increased pain medications due to low back pain, while six of the nine participants increased pain medications for reasons other than low back pain. Since any increase in pain medications automatically considers a participant a non-responder, these six participants are removed from this analysis to eliminate the confounding factor of increases in pain medications for reasons other than low back pain.	120 Days
Treatment Satisfaction	The Treatment Satisfaction Questionnaire asking the participant if they are satisfied with the treatment.	120 Days
Treatment Satisfaction at One Year	The Treatment Satisfaction Questionnaire asking the participant if they are satisfied with the outcome of the treatment. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.	1 Year
Clinical Global Impression of Change	Clinical Global Impression consists of the following question completed by the Investigator prior to unblinding: In your opinion as a clinician, compared to the patient's situation at baseline, would you say the patient is: 1) Much better, 2) Slightly better, 3) About the same, 4) Slightly worse, 5) Much worse.	120 Days
Clinical Global Impression of Change at One Year	Clinical Global Impression consists of the following question completed by the Investigator prior to unblinding: In your opinion as a clinician, compared to the patient's situation at baseline, would you say the patient is: 1) Much better, 2) Slightly better, 3) About the same, 4) Slightly worse, 5) Much worse. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.	1 Year
Change in Opioid Use for Treatment of Low Back Pain at One-Year	Any increase or decrease of dosage or frequency of an opioid taken for the treatment of low back pain was considered a change.	1 Year

Collaborators and Investigators

• Sponsor: Mainstay Medical
• Investigators: Study Chair: Chris Gilligan, MD, MBA, Brigham and Women's Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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. Erratum In: Neuromodulation. 2023 Aug;26(6):1272-1273. doi: 10.1016/j.neurom.2023.03.004.
• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): January 1, 2024

Study Registration Dates

• First Submitted: October 12, 2015
• First Submitted That Met QC Criteria: October 14, 2015
• First Posted (Estimated): October 16, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain
• Other Study ID Numbers: 950057