ReActiv8 Stimulation Therapy vs Optimal Medical Management: A Randomized Evaluation
Phase: NA
Conditions: Chronic Low-back Pain
Sponsor: Mainstay Medical

 
 
 
Title: ReActiv8 Stimulation 
Therapy vs Optimal 
Medical Management: A 
Randomized Evaluation   
NCT04803214 
11-JAN-2024 

RESTORE Clinical Protocol 
The contents of this document are confidential and are not to be reproduced or made available to third parties without prior consent 
from Mainstay Medical and are not to be used in any unauthorized way. 
Page 1 of 47 
Document Number 980012 Rev. D 
11-JAN-2024 
 
 
 
 
 
 
 
 
 
 
 
ReActiv8 Stimulation Therapy vs Optimal Medical 
Management: A Randomized Evaluation (RESTORE) 
Clinical Protocol 
 
Post Market Study 
 
 
 
Sponsor 
MML US Inc. 
2159 India Street, Suite 200 
San Diego, CA 92101 
 
Document Number 980012, Rev. D 
11-JAN-2024 

RESTORE Clinical Protocol 
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from Mainstay Medical and are not to be used in any unauthorized way. 
Page 2 of 47 
Document Number 980012 Rev. D 
11-JAN-2024 
 
 
 
Revision History 
 
Rev 
Change Description 
Effective Date 
A 
Initial release to production 
12-Mar-2021 
B 
• 
Remove EQ-5D eligibility criterion 
• 
Correct Age criterion 
• 
Add Leg Pain description and NRS 
• 
Add EQ-5D sub-analysis 
• 
Aligned study visit activities throughout the document 
• 
Other minor edits 
11-Aug-2021 
C 
• 
Increase number of sites to up to 30 sites 
• 
Clarify that visit windows are a guideline, not a strict 
requirement 
• 
Clarify timing of implant procedure in the Control 
group 
• 
Remove the additional 30 days after randomization 
for the start of visit timing in the Control group 
• 
Clarification of endpoint hypotheses 
• 
Other minor edits 
7-Sep-2022 
D 
• 
Update sponsor address and contact. 
• 
Correct typo in EQ-5D hypotheses 
11-Jan-2024 

RESTORE Clinical Protocol 
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Document Number 980012, Rev. D 
11-JAN-2024 
 
 
Investigator Signature Page 
Investigator Acknowledgement Signature: 
 
I have received and reviewed this Clinical Protocol. I will conduct the study as described. 
 
 
 
Investigator’s Name (print) 
Site Number 
 
 
 
 
Investigator’s Signature 
Date 

RESTORE Clinical Protocol 
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Document Number 980012, Rev. D 
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Table of Contents 
1. Background ............................................................................................................. 6 
1.1. 
Overall Synopsis of the Clinical Study ............................................................................ 11 
2. ReActiv8 Therapy ................................................................................................. 15 
2.1. 
Summary of ReActiv8 .................................................................................................... 15 
2.1.1. 
Implantable Components of ReActiv8 ............................................................................ 15 
2.1.2. 
Non-Implantable Components of ReActiv8 .................................................................... 16 
2.2. 
Indications for Use ......................................................................................................... 16 
2.3. 
Surgical Implantation and Device Activation ................................................................... 16 
2.4. 
Physician and Health Care Personnel Training .............................................................. 16 
3. Study Design ......................................................................................................... 17 
3.1. 
Endpoints....................................................................................................................... 18 
3.1.1. 
Primary Efficacy Endpoint .............................................................................................. 18 
3.1.2. 
Secondary Efficacy Endpoints ........................................................................................ 19 
3.1.3. 
Tertiary Endpoints .......................................................................................................... 20 
3.1.4. 
Safety Assessment ......................................................................................................... 21 
3.1.5. 
Supporting Analyses ...................................................................................................... 22 
3.1.6. 
Health Economics .......................................................................................................... 23 
3.1.7. 
Activity Data Collection ................................................................................................... 23 
3.2. 
Study Visits and Data Collection Schedule ..................................................................... 23 
3.3. 
Patient Selection ............................................................................................................ 26 
3.3.1. 
Inclusion Criteria ............................................................................................................. 26 
3.3.2. 
Exclusion Criteria ........................................................................................................... 26 
4. Study Therapies .................................................................................................... 27 
4.1. 
ReActiv8 Stimulation ...................................................................................................... 27 
4.2. 
Other Therapy During the Study .................................................................................... 27 
5. Study Visits ........................................................................................................... 28 
5.1. 
Informed Consent, Baseline Data, Inclusion Decision .................................................... 28 
5.1.1. 
Eligibility Assessment ..................................................................................................... 29 
5.2. 
Randomization ............................................................................................................... 29 
5.3. 
Implant Procedure (Treatment Group) ........................................................................... 29 
5.4. 
Activation (Treatment Group) ......................................................................................... 29 
5.5. 
1.5-Month Visit ............................................................................................................... 30 
5.6. 
3- and 6-Month Visits ..................................................................................................... 30 
5.7. 
1-Year, 18-Month and 2-Year Visits ............................................................................... 31 
5.8. 
Implant (Control Group) ................................................................................................. 31 
5.9. 
Activation (Control Group) .............................................................................................. 31 
5.10. 13.5-Month and 15-Month Visits (Control Group) ........................................................... 32 
5.11. Unscheduled Visits ........................................................................................................ 32 
5.12. Revision/Explant Procedure ........................................................................................... 32 
6. Anticipated Benefits and Risks ............................................................................32 
6.1. 
Anticipated Benefits ....................................................................................................... 32 
6.2. 
Anticipated Risks ........................................................................................................... 32 
6.3. 
Risk Minimization ........................................................................................................... 33 

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Document Number 980012, Rev. D 
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6.4. 
Patient Deaths ............................................................................................................... 33 
7. Data Management ................................................................................................. 33 
7.1. 
Adverse Event Reporting ............................................................................................... 33 
7.2. 
Reporting of Device Deficiencies.................................................................................... 33 
7.3. 
Management of Protocol Deviations ............................................................................... 33 
7.4. 
Informed Consent .......................................................................................................... 34 
7.5. 
Patient Data Confidentiality ............................................................................................ 34 
7.6. 
Record Keeping ............................................................................................................. 35 
8. Study Management ............................................................................................... 35 
8.1. 
Procedures to Amend the Protocol................................................................................. 35 
8.2. 
Data Monitoring Plan ..................................................................................................... 35 
8.3. 
Sponsor Responsibilities ................................................................................................ 36 
8.4. 
Role of the Sponsor Representatives ............................................................................. 36 
8.5. 
Clinical Investigators ...................................................................................................... 36 
8.6. 
Investigator Selection ..................................................................................................... 37 
8.7. 
Publication Policy ........................................................................................................... 37 
8.8. 
Payments and Costs to Patient ...................................................................................... 38 
8.9. 
Maintaining Compliance ................................................................................................. 38 
8.9.1. 
Study Monitoring ............................................................................................................ 38 
8.9.2. 
Review of Submitted Data .............................................................................................. 38 
8.10. Study Completion .......................................................................................................... 38 
8.11. Suspension or Premature Termination of the Study ....................................................... 39 
9. Administrative Data .............................................................................................. 40 
9.1. 
Name and Address of the Sponsor ................................................................................ 40 
9.2. 
Investigators .................................................................................................................. 40 
9.3. 
Statements of Compliance ............................................................................................. 40 
Appendix 1: MRI Recommended Protocol ................................................................ 41 
Appendix 2: Acronyms ............................................................................................... 43 
Appendix 3: Bibliography ........................................................................................... 44 
Table of Figures 
Figure 1: Review of Pharmacological Therapy ............................................................................ 8 
Figure 2: Study Schema ............................................................................................................ 13 
Figure 3: Study Schema ............................................................................................................ 17 
Figure 4: 11-Point Numerical Rating Scale for Low Back Pain ................................................... 19 
Figure 5: Subject Global Impression of Change (SGIC) Questionnaire ...................................... 20 
Figure 6: Treatment Satisfaction Question ................................................................................. 20 
Table of Tables 
Table 1: Synopsis of the Clinical Study ...................................................................................... 12 
Table 2: Adverse Event Relatedness Categories ....................................................................... 22 
Table 3: Visit Schedule with Recommended Visit Windows ....................................................... 24 
Table 4: Summary Data Collection Schedule – Treatment Group .............................................. 25 
Table 5: Summary Data Collection Schedule – Control Group ................................................... 25 

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Document Number 980012, Rev. D 
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1. Background 
Back pain is the largest cause of years lived with disability globally,1 the leading driver of work 
absenteeism,2 and a leading reason for chronic opioid use.3,4,5 The World Health Organization 
reports that “Low back pain is the most prevalent of musculoskeletal conditions; it affects nearly 
everyone at some point in time and about 4-33% of the population at any given point.”6 Annual 
direct and indirect costs related to low back pain in the US society are estimated to be as high as 
$296 billion annually.7,8 
Acute low back pain usually improves within a matter of weeks, but recurrences are common, and 
pain and disability can become chronic.9 Back pain is generally stated to have become “chronic” 
if it has persisted for more than 3 months. The NIH Task Force on Research Standards for Chronic 
Low Back Pain recommended that Chronic Low Back Pain (CLBP) be defined as a back pain 
problem that has persisted for at least 3 months and has resulted in pain on at least half the days 
in the past 6 months.10 
Although much attention and investment have been applied to surgical treatments for CLBP, only 
20% or less of CLBP patients present with a pathophysiology that can be addressed by additional 
surgical options.11 For the remainder, the most common cause of the CLBP is thought to be 
musculoskeletal or mechanical in nature.12 Depending on local convention and physician 
preference, various terms are used for this type of CLBP: “mechanical chronic low back pain,” 
“musculoskeletal chronic low back pain,” “non-specific low back pain” (NSLBP), or “axial low back 
pain.” There are European clinical practice guidelines for chronic NSLBP13 and UK guidelines for 
management of patients with chronic NSLBP (published by the National Institute for Health and 
Care Excellence – NICE).14 US guidelines for acute and chronic low back pain are similar to the 
European guidelines.15 
It is important to differentiate the two most clinically relevant types of chronic low back pain: 
mechanical CLBP, as noted above, and neuropathic CLBP, frequently a component of the failed 
back surgery syndrome (FBSS). As described below, the pathophysiology of these types of CLBP 
is very different, as are the potentially available therapeutic approaches. 
• 
Neuropathic CLBP, frequently a component of FBSS that does not respond to non-opioid 
medications or physical therapy is well treated with spine surgery and a number of 
neuromodulation modalities including spinal cord stimulation16 and dorsal root ganglion 
stimulation.17 
• 
Mechanical CLBP, which is predominantly nociceptive pain that results from tissue injury 
and inflammation, has no known effective treatment should physical therapy and non- 
opioid medications fail, and outcomes from opioid therapy are poor.18,19 Interventional pain 
approaches including nerve blocks, facet blocks, and radio-frequency ablation may 
provide transient relief but rarely result in long-term relief.20,21,22,23,24,25 To our knowledge, 
no studies have been published demonstrating the effectiveness of spinal cord stimulation 
or dorsal root ganglion stimulation for the treatment of this nociceptive pain syndrome.26 

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Document Number 980012, Rev. D 
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Non-Invasive Therapies 
Recently, a series of systematic reviews of therapies for Low Back Pain were performed to update 
the Clinical Practice Guideline for the American College of Physicians (ACP) and the American 
Pain Society (APS).27,28 With respect to nonpharmacological non-invasive therapies, the authors 
concluded that: “Several nonpharmacologic therapies for primarily chronic low back pain are 
associated with small to moderate, usually short-term effects on pain; findings include new 
evidence on mind-body interventions.”29 
Exercise therapy is frequently prescribed for low back pain. Systematic reviews of the literature 
show that the effectiveness of exercise for chronic low back pain is limited, except for certain 
types of exercise therapy that can be effective in a small subset of patients.30,31 
Many non-invasive conservative therapies have been tried with modest or no success, and 
several reviews are available.32,33,34 Therapies include lumbar extensor strengthening exercises,35 
watchful waiting (i.e., no therapy),36 traction therapy,37 the McKenzie Method of exercise 
therapy,38 various types of energy application including ultrasound, transcutaneous electrical 
nerve stimulation (TENS),39 osteopathic therapy,40 thermotherapy,41 and lumbar stabilization 
exercises.42 
Following failure of conservative therapy for mechanical CLBP, “usual care” or “conventional 
medical management” for mechanical CLBP usually consists of coping mechanisms for pain and 
pain medications (including opioids), which are often increased during the episodic flare-ups of 
pain. 
Pharmacological Therapy Including Opioids 
With respect to pharmacological therapies, the recent systematic review by the ACP guideline 
group (Figure 1) noted that: “Several systemic medications for low back pain are associated with 
small to moderate, primarily short-term effects on pain. New evidence suggests that 
acetaminophen is ineffective for acute low back pain, and duloxetine is associated with modest 
effects for chronic low back pain”.43 
 
From Chou et al., 2017 

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Document Number 980012, Rev. D 
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Figure 1: Review of Pharmacological Therapy 
The ACP also stated “For opioids, evidence remains limited to short-term trials showing modest 
effects versus placebo for chronic low back pain (moderate strength of evidence).44 Trials were 
not designed to assess the risk for overdose or opioid use disorder because of relatively small 
samples, short follow-up, and exclusion of higher risk patients; in addition, many studies used an 
enriched enrollment randomized withdrawal design, which could underestimate harms.45 
Observational studies have found an association between prescribed opioids and serious harms, 
such as overdose,46 and clinical guidelines recommend risk assessment, careful patient selection, 
use of lower doses, and close monitoring and follow-up of patients prescribed these drugs.”47,48 
According to the 2009 to 2010 National Health and Nutrition Examination Survey, opioids are the 
most common prescription drug taken by US adults with CLBP.49 However, outcomes from opioid 
therapy for CLBP are poor.50,51 Concerns about serious avoidable harms, including the 
development of opioid use disorder (OUD), have led the National Institute for Health and Care 
Excellence in the UK to explicitly advise against the use of opioids for CLBP (NICE NG 59), citing 
effects on pain and function that are too small to be clinically important. 52 Despite the lack of 
evidence for effectiveness, surveys show that opioids are prescribed to 45% of patients 
presenting with CLPB to emergency care departments in the US.53 
Data from the first randomized clinical trial with long-term outcomes demonstrated that opioid 
treatment did not confer significantly better benefit with respect to pain-related function when 
compared with non-opioid analgesics and that adverse medication-related events were more 
common among patients receiving opioid therapy.54 Gabapentinoids, which have been prescribed 
as an alternative to opioids, have been shown to be both addictive and ineffective.55 
Interventional Procedures 
Despite a tremendous growth in the number of interventional procedures targeting neuropathic 
low back pain over the last decade, some of which appear to be associated with short or 
intermediate pain relief, 56 their ability to improve function and work status in mechanical CLBP is 
less clear-cut. More importantly, interventional procedures have not resulted in a reduction of 
opioid intake, a crucial outcome for a population at high risk of OUD.57 Furthermore, trials have 
shown a number of interventions to be ineffective for patients whose pain becomes chronic and 
sustained.58,59, 60,61,62,63 
For example, no evidence shows Spinal Cord Stimulation (SCS) to be effective for patients with 
mechanical CLBP. The European guidelines on chronic NSLBP64 state “spinal cord stimulation 
cannot be recommended for nonspecific CLBP.” Similarly, surgery for chronic low back pain 
represents an irreversible intervention that leaves at least one in five patients with a diagnosis of 
failed back surgery syndrome.65 In fact, evidence suggests that surgery performed where chronic 
back pain is the predominant symptom and radicular lower extremity is not prominent, outcomes 
are worse.66, 67 
Despite these facts, many patients have historically opted for back surgery, in part because of the 
poor outcomes of existing nonsurgical therapies. Clinical data suggests that surgical intervention 
is indicated only for approximately 20% of CLBP patients68 Therefore, clinicians and patients 

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Document Number 980012, Rev. D 
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routinely resort to either ineffective and risky chronic opioid therapy or poorly indicated spine 
surgery when CLBP is severe and refractory. 
Societal Cost 
Back pain is the largest cause of years lived with disability globally, the leading driver of work 
absenteeism, and a leading reason for chronic opioid use. 69,70,71 The effects of mechanical CLBP 
can leave many patients disabled and severely restrict their participation in society. Dependence 
on prescribed medication, alcohol or other drugs, and psychological distress can complicate their 
presentation significantly.72 This extracts a large cost from the patients and society related to 
healthcare and disability support. 
In the United Sates, epidemiologic data show that the direct health care costs and indirect costs 
related to work absenteeism are substantial.73,74 
Long-term disability is particularly impactful: “recovery after 12 weeks (of low back pain) is slow 
and uncertain. Fewer than half of those individuals disabled for longer than 6 months return to 
work and, after 2 years of absence from work, the return-to-work rate is close to zero.”75 
Like many chronic conditions, the costs are driven by the small proportion of the population who 
have been sick for the longest period – patients with disability >1 year account for 5% of cases 
but 65% of costs.76,77 Indeed, CLBP is not only a very common cause of work-related disability 
but is also the most expensive with respect to workers’ compensation benefits and medical 
expenses.78 
ReActiv8 Therapy 
Arthrogenic muscle inhibition is the well-known physiological mechanism by which pain in a 
skeletal joint disrupts the motor control to the muscles that stabilize that joint.79,80,81 AMI is a 
presynaptic, ongoing reflex inhibition of musculature surrounding a joint after distension or 
damage to structures of that joint, and serves as a natural response to protect the joint from further 
damage.82 A common example of this is the disruption quadriceps motor control,83 often observed 
after knee injury or knee surgery.84 Persistent AMI may eventually lead to muscle atrophy and 
weakness.85 
A similar mechanism can cause motor control disruption of the key lumbar spine-stabilizing 
muscle – the lumbar multifidus muscle (“multifidus”).86 
The multifidus is an axial load-bearing endurance muscle, and it is the strongest local stabilizer 
of the lumbar spine.87,88 Motor control of the multifidus becomes disrupted following initial injury 
and often persists after the resolution of acute, first-episode low back pain.89 Impaired motor 
control of the multifidus is associated with changes in cortical representation of the multifidus and 
subsequent inability to exert voluntary control.90 
Published studies show that targeted multifidus motor control exercises guided by ultrasound 
biofeedback, that enable a patient to override the normally involuntary motor control system, can 
lead to improvements in back pain.91 Clinical researchers studying the impact of repetitive 
multifidus contraction on low back pain developed the biofeedback method to ensure multifidus 
contraction. This involves dedicating a physical therapist with expertise in ultrasound imaging to 

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Document Number 980012, Rev. D 
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continuously apply ultrasound imaging during physical therapy sessions to guide individual 
patients through motor control exercises and to further repeat such a session daily for several 
weeks or months. The proposed mechanism of action in these studies is the restoration of motor 
control of the multifidus, thereby leading to improved functional spine stability and reduction in 
back pain. However, this approach has not been adopted in clinical practice due to inherent 
practical challenges, economic difficulties, and patient compliance issues. 
Electrical stimulation to facilitate motor control restoration by causing muscle contractions is being 
used successfully with other skeletal muscles. In particular, stimulation via superficial (skin) 
electrodes over the motor point of the quadriceps can restore neural drive and facilitate 
rehabilitation of the muscle in patients following total knee arthroplasty92 or other surgical 
procedures.93,94 Painful knee osteoarthritis can be treated without surgery but may also lead to 
pain-mediated inhibition of neural drive to the quadriceps, which can be treated effectively with 
electrical stimulation.95 
Mainstay Medical Limited (“Mainstay”) has developed the ReActiv8 neurostimulation system 
(“ReActiv8” or “the device”) to treat mechanical CLBP by incorporating the principles of these prior 
approaches. ReActiv8 targets restoration of neuromuscular control by delivering electrical 
stimulation to the medial branch of the dorsal ramus of the spinal nerve to cause episodic 
contraction of the multifidus muscle, to override the underlying arthrogenic muscle inhibition of 
the multifidus. Restoration of neuromuscular control of the multifidus is expected to improve 
functional stability of the spine and reduce mechanical CLBP.96 
The ReActiv8 System obtained CE Marking on 24 MAY 2016, TGA approval 05 DEC 2019, and 
FDA PMA approval on 16 JUN 2020. 
Conclusions 
Thus, current pharmacological, conservative, and interventional therapies do not offer clinically 
relevant long-term improvement to the refractory mechanical CLBP population that does not get 
pain relief from physical therapy and non-opioid medications. 
As a result, these patients are often prescribed stronger agents such as opioids as well as 
gabapentinoids in an effort to manage pain, despite evidence that such drugs may cause more 
harm than benefit. Outcomes from opioid therapy for chronic low back pain are poor,97,98 and 
alternatives such as gabapentinoids have also been shown to be ineffective in this population.99 
Given the considerable personal suffering, familial impact, and societal costs, improving treatment 
effectiveness for patients with intractable mechanical CLBP represents an important public health 
challenge. 
The development of novel, effective, non-opioid therapies for mechanical CLBP addresses a 
critical unmet clinical need and will greatly contribute to solving the public health crisis of opioid 
use disorder. Such therapies should demonstrate a multidimensional benefit for mechanical CLBP 
sufferers, including reduction in pain alongside improvements in physical and social function, 
overall quality of life, and reduction of opioid intake. 

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Document Number 980012, Rev. D 
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1.1. Overall Synopsis of the Clinical Study 
This study is a prospective, randomized study comparing ReActiv8 Therapy to Optimal Medical 
Management (OMM), where OMM means the patient has been managed according to available 
guideline-directed treatments100 (e.g., medication, physical therapy, injections), and are intending 
to continue with their existing course of care during the study. OMM will follow physician treatment 
practices per the guidelines such that it will be individualized to meet the patient needs. A synopsis 
of the study in tabular form is shown in Table 1. 
All patients who satisfy the enrollment criteria are randomized (1:1) to receive either ReActiv8 
(Treatment group) or OMM (Control group). 
After randomization, those in the Treatment group will be implanted, and then all patients will be 
followed at the following timepoints post-implant: 1.5 months, 3 months, 6 months, 1 year, 18 
months, and 2 years. After the 1-year visit, patients in the Control group may elect to be implanted 
with the ReActiv8 device and, in addition to the visits noted above, will have follow-up visits at 
13.5 months and 15 months. Patients in the Control group who are not implanted with a ReActiv8 
device after the 1-year visit will be exited from the study at that time. 
The primary efficacy endpoint is a comparison of mean change in Oswestry Disability Index (ODI) 
at 1 year compared to baseline. 
Secondary and tertiary endpoints will be assessed at the 1-year visit compared to baseline, 
including change in Numerical Rating Scale (NRS) Pain score, a composite of change in ODI and 
change in NRS Pain score, change in EQ-5D Quality of Life, Percent Pain Relief, Subject Global 
Impression of Change (SGIC), and Treatment Satisfaction. 
Related adverse events (AEs) and all serious adverse events (SAEs) will be reported from 
enrollment through study exit. 

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Document Number 980012, Rev. D 
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Table 1: Synopsis of the Clinical Study 
Study Purpose 
To compare the effectiveness of ReActiv8 to OMM for the treatment of intractable chronic low 
back pain (CLBP). 
Indications for 
Use 
The ReActiv8 System is indicated for bilateral stimulation of the L2 medial branch of the dorsal 
ramus as it crosses the L3 transverse process as an aid in the management of intractable 
chronic low back pain associated with multifidus muscle dysfunction, as evidenced by imaging 
or physiological testing in adults who have failed therapy including pain medications and 
physical therapy and are not candidates for spine surgery. 
Study Device 
ReActiv8 System 
Study Design 
Prospective, randomized study comparing ReActiv8 to OMM. See Figure 2 for the study 
schema. 
Treatment Arm 
ReActiv8 Therapy 
Control Arm 
OMM 
Randomization 
Patients meeting all eligibility criteria will be randomized to either the Treatment group or the 
Control group. Randomization will be performed according to a random permuted block design 
stratified by clinical site with a 1:1 allocation ratio for Treatment vs Control. 
Sample Size 
A minimum of 204 randomized patients are required to sufficiently power the primary endpoint. 
To account for attrition, approximately 230 patients will be randomized. 
Number of Sites Up to 30 sites 
Primary 
Endpoint 
The primary endpoint is a comparison of 1-year mean change from baseline in ODI between 
the Treatment and Control groups. 
Secondary 
Endpoints 
1. Comparison of 1-year change from baseline in LBP NRS between Treatment and Control 
2. Comparison of 1-year change from baseline in EQ-5D between Treatment and Control 
Tertiary 
Endpoints 
1. Comparison of Percent Pain Relief at 1 year between Treatment and Control 
2. Comparison of Subject Global Impression of Change at 1 year between Treatment and 
Control 
3. Comparison of Treatment Satisfaction at 1 year between Treatment and Control 
4. Comparison at 1 year of the percent of patients with a change in ODI ≥ 15 or reduction in 
NRS ≥ 50% (and no decrease in either measure) between Treatment and Control 
5. Comparison at 1 year in the change from baseline in Leg Pain NRS between Treatment 
and Control 
Additional 
Supporting 
Analyses 
1. Comparison between Treatment and Control in the of responder rate in ODI at 1 year, 
where a change ≥15 points is considered a responder 
2. Comparison between Treatment and Control in the cumulative proportion of responder rate 
in ODI at 1 year 
3. Comparison between Treatment and Control in the of responder rate in NRS at 1 year, 
where a change ≥50% is considered a responder 
4. Comparison between Treatment and Control in the cumulative proportion of responder rate 
in NRS at 1 year 
5. Within group changes in all analyses will be assessed at 2 years 
6. Cost-effectiveness assessment including: 
• Change in work status, work-days missed and ability to do their work at 1 and 2 years 
compared to baseline 
• Health care utilization (office visits, hospital visits, emergency room visits, and other 
therapies such as physical therapy) at 1 and 2 years compared to baseline 
7. Activity monitoring, including the number of steps and amount of sleep, will be collected on 
a subset of patients and assessed through 2 years compared to baseline 
8. Additional ad hoc analyses may also be conducted 

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Adverse Events Adverse events related to the system, procedure, or therapy, and all serious adverse events 
will be reported from enrollment through study exit and will be summarized. 
Study Duration Approximately 4 years from first enrollment to the last 2-year visit 
Study Schedule 
The study visit schedule will vary slightly between the groups to account for the Treatment 
group bring implanted after the randomization visit. After the 1-year visit, patients in the Control 
group may elect to be implanted with the ReActiv8 device and will continue to be followed 
through the 2-year visit. Patients in the Control group who do not receive a device after the 1- 
year visit will be exited from the study at that time. 
For the Treatment group, visit timing for all visits will be based on Activation. For the Control 
group visit timing will be Randomization for visits through the 1-year visit. After those in the 
Control group are implanted, the remaining visit timing will be based off their Activation visit. 
Figure 2: Study Schema 
Eligibility 
Criteria 
Inclusion Criteria 
1. Indicated for the ReActiv8 System 
• Age ≥21 years 
• Evidence of lumbar multifidus muscle dysfunction 
• Intractable Chronic Low Back Pain that has persisted >6 months prior to enrollment, 
resulting in pain most of the days in the 12 months prior to enrollment 
• Failed therapy including pain medications and physical therapy 
• Not a candidate for spine surgery 
2. Low Back Pain NRS of ≥6 and ≤9 
3. Oswestry Disability Index score ≥30 and ≤60 
4. Willing and capable of giving Informed Consent 
5. Able to comply with this protocol 
6. On Optimal Medical Management per the Investigator 

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Eligibility 
Criteria 
Exclusion Criteria 
1. Contraindicated for the ReActiv8 System 
• Unable to operate the ReActiv8 System 
• Unsuitable for ReActiv8 implant surgery 
2. BMI > 35 
3. Back Pain characteristics: 
a. Any surgical correction procedure for scoliosis at any time, or a current clinical 
diagnosis of moderate to severe scoliosis (Cobb angle ≥25°)52 
b. An independent MRI assessment identifying a pathology that is likely the cause of the 
CLBP and is amenable to surgery 
4. Leg pain described as being worse than back pain, or radiculopathy (neuropathic pain) 
below the knee 
5. Surgical or other procedures exclusions: 
a. Any previous back surgery (e.g., laminectomy, discectomy, spinal fusion) at or below 
segmental level T8 
b. Any previous thoracic or lumbar sympathectomy 
c. Any lumbar rhizotomies within the past 12 months 
d. Any lumbar nerve blocks within the past 30 days 
e. Any previous or existing neuromodulation devices (e.g., drug pump, spinal cord 
stimulation, and/or peripheral nerve stimulation) 
6. Other clinical conditions: 
a. Pregnant or planning to be pregnant in the next 12 months 
b. Any condition unrelated to CLBP such as muscle wasting, muscle atrophy, or 
progressive neurological disease which, in the opinion of the Investigator, could limit 
physical movement or compliance with the protocol, or interfere with the assessment 
of efficacy 
c. Evidence of an active disruptive psychological or psychiatric disorder or other known 
condition significant enough to impact perception of pain, compliance with intervention 
and/or ability to evaluate treatment outcome (e.g., active depression, bipolar disease, 
Alzheimer’s disease) as determined by the Investigator in consultation with a 
psychologist or psychiatrist as appropriate 
d. An opioid addiction or drug-seeking behavior, as determined by the Investigator 
e. Any active malignant disease 
f. Any active infection in the vicinity of the implant site or any systemic infection 
g. Poorly controlled diabetes (Type I or Type II) determined by HbA1c >8 
7. General exclusions: 
a. Current smoker 
b. Current or planned participation in any other clinical trial during the study 
c. A condition currently requiring or likely to require use of MRI or diathermy 
d. Life expectancy less than one year 
e. A pending or approved financial compensation claim (e.g., worker’s compensation 
claim, long term disability claims, injury claim under litigation) 
 

RESTORE Clinical Protocol 
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Page 15 of 47 
Document Number 980012, Rev. D 
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2. ReActiv8 Therapy 
2.1. Summary of ReActiv8 
ReActiv8 is an implantable electrical stimulation system consisting of the following components: 
1. Implantable Pulse Generator (IPG) – (pre-loaded with IPG Firmware Code and packaged 
with a Torque Wrench to aid in implant procedure) 
2. Percutaneous Leads (with Stylet and Suture Sleeves) 
3. Application Software 
4. Programmer Wand 
5. Activator (pre-loaded with Activator Firmware Code) 
6. Magnet 
7. Tunneler 
The ReActiv8 Programmer Wand and Application Software are provided with a commercially 
available laptop computer and AC adapter. Commercially available surgical tools such as a 7Fr 
Introducer Kit is used at implant and is not part of ReActiv8. 
ReActiv8 delivers stimulation via electrodes placed adjacent to the medial branch of the dorsal 
ramus nerve at the preferred location as it crosses the L3 transverse process. The electrodes are 
located at the distal end of a Stimulation Lead that is connected to an implantable pulse generator 
(IPG) placed in a surgical pocket typically above the buttocks (in a place similar to that used in 
Spinal Cord Stimulation implants). Two leads are placed (one each left and right side) and 
connected to the IPG. The IPG is externally programmable via Application Software stored on a 
laptop computer. Stimulation is manually initiated by an external device (Activator) and can be 
stopped with the Activator or Magnet. 
The leads incorporate a fixation mechanism that consists of two sets of 3-point tines – one set 
facing forward and one set facing backwards. The tines are positioned to lie on either side of the 
intertransversarii lateralis, thus reducing the risk of lead migration by either advancement or 
retraction. The lead body is a polyurethane tube containing the lead conductor, incorporating a 
lumen to allow passage of a stylet. Refer to the Implant and Programming Manual (990070-001) 
for more detail on device specifications and operation. 
2.1.1. 
Implantable Components of ReActiv8 
The ReActiv8 IPG, and the two sizes of leads (45 cm and 65 cm) are designed for permanent 
implant. The implantable components of ReActiv8 are supplied sterile and are intended for single 
use only. 
• 
Model 5100 ReActv8 Implantable Pulse Generator 
• 
Model 8145 ReActiv8 Percutaneous Lead, 45 cm length 
• 
Model 8165 ReActiv8 Percutaneous Lead, 65 cm length 

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Document Number 980012, Rev. D 
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2.1.2. 
Non-Implantable Components of ReActiv8 
The Torque Wrench and Stylet are provided to facilitate implantation of the IPG and leads. The 
Application Software and Programmer Wand are used with a laptop computer to communicate 
with the IPG in order to program the IPG operational mode and settings, read history data from 
the IPG, and obtain IPG and lead status information. The Activator is used to initiate and/or 
suspend stimulation. The Magnet is used to enter Magnet Mode (with Magnet Mode operation 
determined by the programmed parameters of the IPG). 
The non-implantable components of the ReActiv8 system are: 
• 
Model 7000 ReActiv8 Activator 
• 
Model 4000 ReActiv8 Magnet 
• 
Model 5500 ReActiv8 Torque Wrench 
• 
Version 1.0.1.6 (English) and 1.0.1.9 (Multilanguage) Application Software 
• 
Model 6000 Programmer Wand 
• 
Model TUN1 Tunneler 
The ReActiv8 Programmer Wand and Application Software are provided with a commercially 
available laptop computer and AC adapter. 
2.2. Indications for Use 
The ReActiv8 System is indicated for bilateral stimulation of the L2 medial branch of the dorsal 
ramus as it crosses the transverse process at L3 as an aid in the management of intractable 
chronic low back pain associated with multifidus muscle dysfunction, as evidenced by imaging or 
physiological testing in adults who have failed therapy including pain medications and physical 
therapy and are not candidates for spine surgery. 
2.3. Surgical Implantation and Device Activation 
The surgical implantation procedure, device programming, and use by the patient are per the 
Implant and Programming Manual (990070-001) and the User Manual (990071-001). 
2.4. Physician and Health Care Personnel Training 
All physicians who will implant any portion of the ReActiv8 system must have participated in 
product training. 

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Document Number 980012, Rev. D 
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3. Study Design 
The ReActiv8 Stimulation Therapy vs Optimal Medical Management: A Randomized Evaluation 
(RESTORE) study is a prospective, randomized study comparing ReActiv8 therapy to Optimal 
Medical Management (OMM). Patients meeting all eligibility criteria will be randomized to either 
the Treatment group (ReActiv8) or the Control group (OMM). Randomization will be performed 
according to a random permuted block design stratified by clinical site with a 1:1 allocation ratio. 
The primary endpoint will be a comparison of the change in Oswestry Disability Index (ODI) at 1 
year between the Treatment and Control groups. After 1-year visit, all patients in the Control group 
may elect to receive a ReActiv8 device and will continue to be followed through the 2-year visit. 
Patients in the Control group who do not receive a device after the 1-year visit will be exited from 
the study at that time. 
A minimum of 204 evaluable patients is required to sufficiently power the primary endpoint. To 
allow for attrition, approximately 230 patients will be randomized at up to 30 clinical sites. To 
account for screen failures prior to randomization approximately 400 patients may be enrolled. 
The study visit schedule will vary slightly between the groups to allow for those in the Treatment 
group to be implanted after the randomization visit. After the 1-year visit, patients in the Control 
group may elect to be implanted. The study schema is provided in Figure 3. 
 
Figure 3: Study Schema 
 
 
Total study duration is anticipated to be approximately 4 years from first enrollment to the last 2- 
year visit. 

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Document Number 980012, Rev. D 
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3.1. 
Endpoints 
3.1.1. 
Primary Efficacy Endpoint 
3.1.1.1. 
ODI 
Oswestry Disability Index (ODI) is a disease specific assessment of the disabling effects of back 
pain.48 The ODI covers 1 item on pain and 9 items on activities of daily living (personal care, lifting, 
walking, sitting, standing, sleeping, sex life, social life, and traveling). ODI is reported as a score 
from 0 to 100. 
The relevance of changes in ODI has been explored by many authors, and discussions abound 
on Minimal Clinical Important Difference (MCID), Minimally Important Change (MIC) and the like. 
Fairbank, et al., suggest a minimally important change is 15 points.101 
Hypothesis Test 
The Primary endpoint is a comparison between the Treatment group and Control group of 
average change in ODI at 1 year compared to baseline. 
The ODI efficacy endpoint will be tested under the following hypotheses: 
H0: µODIT - µODIC ≥ 0 
HA: µODIT - µODIC < 0 
Where µODIT is the mean change in ODI in the Treatment group and µODIC is the mean change 
in ODI in the Control group at the 1-year visit. These hypotheses will be tested using the 1-year 
treatment effects contrast obtained from a mixed model for repeated measures (MMRM). The 
two-sided p-value for the equality null hypothesis will be reported as well as the two-sided adjusted 
95% confidence interval for the difference in mean changes. Superiority will only be claimed if 
p<0.05 and the mean change is more negative (greater improvement) for the Treatment group 
compared to the Control group. This is equivalent to specifying a one-sided test at α=0.025. 
3.1.1.2. 
Sample Size Rationale 
The sample size for the study is determined under the following assumptions for the primary 
efficacy endpoint, which are based on a prior study of ReActiv8102, and approximately the MMRM 
test by its corresponding unadjusted t-test. All else being equal, this is a conservative estimate of 
power since control for baseline and inclusion of intermediate time points is not accounted for. 
• 
Minimum power of 80% 
• 
Type I error of 5% 
• 
Assumed mean change in Treatment group: 18.2 
• 
Assumed mean change in Control group: 12.2 
• 
Pooled Standard Deviation: 15 
Under the above assumptions, a minimum of 204 evaluable patients is required in order to 
demonstrate superiority of the ReActiv8 treatment. To account for attrition, approximately 230 
patients will be enrolled and randomized. 

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Document Number 980012, Rev. D 
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3.1.2. 
Secondary Efficacy Endpoints 
The same MMRM will be applied to NRS and EQ-5D. To control type 1 error, the p-values for 
superiority at 1 year will only be interpreted as inferential if the superiority for improvements in 
Year 1 ODI is demonstrated at 2-sided type 1 error rate of α=0.05 (with hypothesized 
directionality). The Hochberg method (Hochberg 1988103) will be used to control type 1 error 
among these two secondary endpoints. 
3.1.2.1. 
Low Back Pain NRS 
Average Low Back Pain will be measured using the 11-point Numerical Rating Scale for Low Back 
Pain (Figure 4), as recommended by IMMPACT.40 Specifically, the NRS scale for “average low 
back pain in the last 24 hours” will be used. 
Figure 4: 11-Point Numerical Rating Scale for Low Back Pain 
The endpoint will compare change from baseline in NRS between Treatment and Control groups 
at the 1-year visit. 
Hypothesis Test 
The NRS objective will be assessed by the following hypotheses: 
H0: µNRST - µNRSC ≥ 0 
HA: µNRST - µNRSC < 0, 
where µNRST is the mean change in NRS from baseline to 1 year in the Treatment group and 
µNRSC is the mean change in NRS from baseline to 1 year in the Control group. These 
hypotheses will be tested using 1-year contrast from an MMRM as described above. 
3.1.2.2. 
EQ-5D 
The EQ-5D-5L (referred to as EQ-5D throughout this document) is a quality-of-life questionnaire 
comprising of the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and 
anxiety/depression. 
Population norms for EQ-5D for various populations have been reported, and categorized by age, 
gender and social class. EQ-5D is reported as an index up to 1.00. An EQ-5D index score of <0 
is possible in some circumstances. 
The endpoint will compare change from baseline in EQ-5D between Treatment and Control 
groups at the 1-year visit. 
Hypothesis Test 
The EQ-5D efficacy objective will be tested under the following hypotheses: 
H0: µEQ5DT - µEQ5DC ≤ 0 
HA: µEQ5DT - µEQ5DC > 0 

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Document Number 980012, Rev. D 
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Where µEQ5DT is the mean change in EQ-5D (index score) in the Treatment group and µEQ5DC 
is the mean change in EQ-5D in the Control group. These hypotheses will be tested using 1-year 
contrast from an MMRM as described above. 
3.1.3. 
Tertiary Endpoints 
3.1.3.1. 
Percent Pain Relief (PPR) 
Percent Pain Relief (PPR) is a question asked to the patient in which the patient is asked to report 
the percent pain relief at the time of the current visit compared to the pain at baseline. 
The endpoint will compare PPR at the 1-year visit between Treatment and Control groups in 
descriptive analyses. 
3.1.3.2. 
Subject Global Impression of Change (SGIC) 
Subject Global Impression of Change (SGIC) is based on the “Subject Global Impression of 
Change” as described by Farrar.65 The patient is presented with a questionnaire with 7 choices, 
as shown in Figure 5. 
Figure 5: Subject Global Impression of Change (SGIC) Questionnaire 
The endpoint will compare SGIC at the 1-year visit between Treatment and Control groups in 
descriptive analyses. 
3.1.3.3. 
Treatment Satisfaction 
Treatment satisfaction will be measured by a single question as shown in Figure 6. 
 
Figure 6: Treatment Satisfaction Question 
The endpoint will compare Treatment Satisfaction at the 1-year visit between Treatment and 
Control groups. 
3.1.3.4. 
ODI and NRS Composite 
Patients suffering from CLBP are continuously balancing their activity level with their level of pain. 
As their condition improves, patients make personal choices on whether to increase their level of 
activity while tolerating a certain level of pain, or to continue with the same level of activity as 
earlier but with less discomfort, or somewhere in between. These choices are based on the 

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Document Number 980012, Rev. D 
11-JAN-2024 
 
 
patients’ individual circumstances and preferences. Therefore, when evaluating a therapy for 
CLBP, an evaluation of improvements in pain interpreted in conjunction with functional 
improvements allows for a more comprehensive assessment of the therapy. 
This endpoint will compare the percent of patients with a change in ODI ≥ 15 or a reduction in 
NRS ≥ 50% (and no decrease in either measure) at the 1-year visit between Treatment and 
Control groups. 
3.1.3.5. 
Leg Pain NRS 
Average Leg Pain will be measured using an 11-point Numerical Rating Scale for Leg Pain. The 
patient will rate his/her average leg pain in the last 24 hours on a scale from zero to ten, where 
zero is no pain and ten is the worst imaginable pain 
The endpoint will compare change from baseline in Leg Pain NRS between Treatment and 
Control groups at the 1-year visit. 
3.1.4. 
Safety Assessment 
Reportable adverse events (AEs) are those related to the device, procedure, stimulation or other 
therapies utilized to treat LBP, and all serious adverse events (SAEs), whether related or not. 
All reportable AEs will be documented and reported from the time of informed consent through 
the end of the study with summary statistics presented for observed rates. No formal statistical 
hypotheses will be tested in the safety assessment. The following definitions are used: 
Adverse Event (AE): 
An AE is defined as any undesirable clinical occurrence that affects the health or safety of the 
patient. 
Serious Adverse Event (SAE): 
An SAE is defined as an AE that led to death, or led to serious deterioration in the health of the 
patient, that either resulted in: 
1. a life-threatening illness or injury, or 
2. a permanent impairment of a body structure or a body function, or 
3. in-patient or prolonged hospitalization, 
4. congenital anomaly/birth defect, or 
5. medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function. 
Unanticipated Adverse Device Effect (UADE): 
A UADE means any serious adverse effect on health or safety or any life-threatening problem or 
death caused by or associated with a device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the protocol or application, or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare 
of patients. 
Adverse Event Relatedness: 
The Investigator must determine whether the event was related to the device, stimulation, 
procedure, and/or other therapies. The categories used for relatedness are listed in Table 2. 

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Document Number 980012, Rev. D 
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Table 2: Adverse Event Relatedness Categories 
Related to Device 
Events reasonably anticipated to be related to the physical presence 
of the device (e.g., lead fracture requiring revision). 
Related to 
Stimulation 
Events reasonably anticipated to be related to stimulation, especially 
those that appear when the device is on and disappear when the 
device is off (e.g., undesired sensation experienced only when the 
device is turned on). 
Related to 
Procedure 
Events reasonably anticipated to be related to the implant procedure. 
Related to Other 
Therapies 
Events reasonably anticipated to be related to treatments being utilized 
to treat the patient’s LBP (e.g., medications, injections, physical 
therapy). 
AE Notes: 
1. AEs that would be reasonably expected to be associated with any surgical procedure and 
are not specific to the ReActiv8 procedure (e.g., anesthesia associated nausea, transient 
post-op surgical site pain) will not be collected. 
2. If an AE leads to multiple outcomes that sequentially worsen, only the worst AE is reported. 
For example, a hematoma leading to infection is reported as a single AE for the infection. 
3. Any current condition that is recorded as a pre-existing condition is not an AE, unless there 
is a worsening of that condition in terms of nature, severity, or degree of incidence. 
4. Removing, suspending or stopping use of ReActiv8 due to pain relieved is not an AE. 
5. Planned hospitalization for a procedure required by this protocol is not an AE. 
6. Symptoms felt during a programming session are not considered AEs unless they are 
caused by the final programming parameters and persist after the programming session. 
7. Lack of efficacy or diminished therapeutic response does not constitute an AE since failure 
to receive therapeutic benefit is an issue of efficacy, not safety. This includes symptoms that 
recur in the context of device deficiency leading to loss of therapy. If the recurring symptoms 
are not worse than at baseline, it is not considered an AE. 
8. Removal or replacement of any part of the device due to malfunction would be considered 
a device related AE, since it requires the patient to undergo a surgical procedure. 
9. Death should not be recorded as a separate AE, but rather as an outcome of the specific 
SAE which led to the patient’s death. 
3.1.5. 
Supporting Analyses 
The supporting efficacy analyses will include: 
• Comparison between the Treatment and Control groups in the of responder rate in ODI at 
the 1-year visit, where a change ≥15 points is considered a responder 
• Comparison between the Treatment and Control groups in the cumulative proportion of 
responder rate in ODI at the 1-year visit 
• Comparison between the Treatment and Control groups in the of responder rate in NRS at 
the 1-year visit, where a change ≥50% is considered a responder 
• Comparison between the Treatment and Control groups in the cumulative proportion of 
responder rate in NRS at the 1-year visit 
• Within group changes in all analyses will also be assessed at the 2-year visit 

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Document Number 980012, Rev. D 
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• Endpoints will be further analyzed by baseline EQ-5D index score 
• Health economic outcome measures at the 1- and 2-year visits will be compared to baseline 
• Activity monitoring will be collected on a subset of patients and assessed through the 2-year 
visit and compared to baseline 
• Additional ad hoc analyses may also be conducted 
 
3.1.6. 
Health Economics 
Health economic outcome measures to be recorded will include: 
• Work status, work-days missed and ability to do their work the year prior to baseline, and at 
the 1- and 2-year visits 
• Health care utilization (office visits, hospital visits, emergency room visits, and other 
therapies such as physical therapy) the year prior to baseline and at the 1- and 2-year visits 
3.1.7. 
Activity Data Collection 
Activity data will be collected on a subset of patients who: 
• 
have an activity tracker that they have used regularly for at least three months, 
• 
agree to wear the activity tracker for the duration of the study, and 
• 
agree to have activity data transmitted to be saved in the database. 
After signing consent and meeting enrollment criteria, activity data from at least 2 weeks prior to 
enrollment will be downloaded. Activity data will be collected continuously while the patient is 
wearing the activity tracker and downloaded periodically by the patient. To help ensure complete 
data are obtained, a download of the data will also occur at each study visit. 
The time period from Baseline through Activation will serve as the Baseline assessment of activity, 
with the following exceptions: 
• 
Patients in the Treatment group would be expected to be moving less during the healing 
process post-procedure; therefore, activity data will be excluded between the Implant and 
Activation visits (approximately 2 weeks). 
• 
Patients in the Control group will have the 2-week time period prior to Activation excluded 
to align with the timeframe excluded for the Treatment group. 
Activity data to be collected include: 
• 
Distance and Number of Steps 
• 
Stationary Time 
• 
Sleep Data 
 
3.2. Study Visits and Data Collection Schedule 
The study visit schedule is provided in Table 3. The study visit schedule will vary slightly between 
the groups to account for the Treatment group being implanted after the randomization visit. For 
the Treatment group, visit timing for all visits will be based on Activation. For the Control group 
visit timing through the 1-year visit will be based on Randomization. After those in the Control 
group are implanted, the timing of the remaining visits will be based on the Activation visit. 

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Document Number 980012, Rev. D 
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Table 3: Visit Schedule with Recommended Visit Windows 
Visit 
Treatment 
Control 
Informed consent, baseline 
✓ 
✓ 
Randomization (Approx. 14 days post baseline) 
✓ 
✓ 
ReActiv8 implant (Approx. 14 days post randomization) 
✓ 
Activation (Approx. 14 days post implant) 
✓ 
 
1.5-month (45 ± 14 days) 
✓ 
✓ 
3-month (90 ± 30 days) 
✓ 
✓ 
6-month (180 ± 30 days) 
✓ 
✓ 
1-year (365 ± 60 days) 
✓ 
✓ 
ReActiv8 implant (within 60 days of the 1-year visit) 
✓ 
Activation (Approx. 14 days post implant) 
✓ 
13.5-month (410 ± 14 days) 
✓ 
15-month (450 ± 30 days) 
✓ 
18-month (540 ± 30 days) 
✓ 
✓ 
2-year (730 ± 60 days) 
✓ 
✓ 
 
A summary of the data collection schedule is shown for the Treatment group in Table 4 and for 
the Control group in Table 5. 

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Document Number 980012, Rev. D 
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✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Related AEs & All SAEs 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Activity Data Download (if applicable) 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Health Care Utilization 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
SGIC 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Leg Pain Description and NRS 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
EQ-5D 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
ODI 
✓ 
✓ 
Multifidus Dysfunction Assessment 
✓ 
✓ 
Screening Data & Physical Exam 
Table 4: Summary Data Collection Schedule – Treatment Group 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 5: Summary Data Collection Schedule – Control Group 
 
 
 
 
 
 
 
 
 
 
MRI 
 
DASS21 
 
Low Back Pain NRS 
 
Low Back Pain Description 
 
Percent Pain Relief 
 
Treatment Satisfaction 
 
Work Status Evaluation 
 
Pain Treatments Log 
 
Device Measurements Download 
Screening Data & Physical Exam 
MRI 
Multifidus Dysfunction Assessment 
DASS21 
ODI 
Low Back Pain NRS 
EQ-5D 
Low Back Pain Description 
Leg Pain Description and NRS 
Percent Pain Relief 
SGIC 
Treatment Satisfaction 
Health Care Utilization 
Work Status Evaluation 
Activity Data Download (if applicable) 
Pain Treatments Log 
Related AEs & All SAEs 
Device Measurements Download 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Unscheduled Visit 
Unscheduled Visit 
2-Year Visit 
2-Year Visit 
18-Month Visit 
18-Month Visit 
15-Month Visit 
1-Year Visit 
13.5 Month Visit 
ReActiv8 Implant 
& Activation 
6-Month Visit 
3-Month Visit 
1-Year Visit 
1.5 Month Visit 
6-Month Visit 
ReActiv8 Implant 
& Activation 
Randomization 
Informed Consent 
& Baseline 
3-Month Visit 
1.5 Month Visit 
Randomization 
Informed Consent 
& Baseline 

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3.3. 
Patient Selection 
3.3.1. 
Inclusion Criteria 
1. Indicated for the ReActiv8 System 
• Age ≥21 years 
• Evidence of lumbar multifidus muscle dysfunction 
• Intractable Chronic Low Back Pain that has persisted >6 months prior to enrollment, 
resulting in pain most of the days in the 12 months prior to enrollment 
• Failed therapy including pain medications and physical therapy 
• Not a candidate for spine surgery 
2. Low Back Pain NRS of ≥6 and ≤9 
3. Oswestry Disability Index score ≥30 and ≤60 
4. Willing and capable of giving Informed Consent. 
5. Able to comply with this protocol 
6. On Optimal Medical Management per the Investigator 
3.3.2. 
Exclusion Criteria 
1. Contraindicated for the ReActiv8 System 
• Unable to operate the ReActiv8 System 
• Unsuitable for ReActiv8 implant surgery 
2. BMI > 35 
3. Back Pain characteristics: 
a. Any surgical correction procedure for scoliosis at any time, or a current clinical diagnosis 
of moderate to severe scoliosis (Cobb angle ≥25°)52 
b. An independent MRI assessment identifying a pathology that is likely the cause of the 
CLBP and is amenable to surgery 
4. Leg pain described as being worse than back pain, or radiculopathy (neuropathic pain) 
below the knee 
5. Surgical or other procedures exclusions: 
a. Any previous back surgery (e.g., laminectomy, discectomy, spinal fusion) at or below 
segmental level T8 
b. Any previous thoracic or lumbar sympathectomy 
c. Any lumbar rhizotomies within the past 12 months 
d. Any lumbar nerve blocks within the past 30 days 
e. Any previous or existing neuromodulation devices (e.g., drug pump, spinal cord 
stimulation, and/or peripheral nerve stimulation) 
6. Other clinical conditions: 
a. Pregnant or planning to be pregnant in the next 12 months 
b. Any condition unrelated to CLBP such as muscle wasting, muscle atrophy, or progressive 
neurological disease which, in the opinion of the Investigator, could limit physical 
movement or compliance with the protocol, or interfere with the assessment of efficacy 

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c. Evidence of an active disruptive psychological or psychiatric disorder or other known 
condition significant enough to impact perception of pain, compliance with intervention 
and/or ability to evaluate treatment outcome (e.g., active depression, bipolar disease, 
Alzheimer’s disease) as determined by the Investigator in consultation with a psychologist 
or psychiatrist, as appropriate 
d. An opioid addiction or drug-seeking behavior, as determined by the Investigator 
e. Any active malignant disease 
f. 
Any active infection in the vicinity of the implant site or any systemic infection 
g. Poorly controlled diabetes (Type I or Type II) determined by HbA1c >8 
7. General exclusions: 
a. Current smoker 
b. Current or planned participation in any other clinical trial during the study 
c. A condition currently requiring or likely to require use of MRI or diathermy 
d. Life expectancy less than one year 
e. A pending or approved financial compensation claim (e.g., worker’s compensation claim, 
long term disability claims, injury claim under litigation) 
 
4. Study Therapies 
4.1. ReActiv8 Stimulation 
Patients will be instructed to deliver stimulation for 60 minutes per day up to the 1-year visit, in 
two sessions of 30 minutes each. The IPG contains data logging of the times for start and stop of 
each stimulation session, and the data will be collected and recorded at each follow up visit. 
Note: ReActiv8 does not allow stimulation greater than the maximum programmed number of 
minutes in any day (midnight to midnight), which is set at 60 by default. 
Note: A session can be prematurely stopped with the Magnet or the Activator, and stimulation 
can be restarted to complete the session later in the day. 
Following the 1-year visit, patients will be advised to continue to deliver stimulation for 60 minutes 
per day (in two 30-minute sessions) but will be permitted to reduce the amount of stimulation as 
desired. 
Patients should be encouraged to contact site personnel if they find that they are unable to 
complete a session for any reason. 
4.2. Other Therapy During the Study 
Other therapy during the study should be managed per the OMM plan developed using the 
RESTORE Treatment Guidelines document (980016), to the extent possible. Any therapy 
changes during the study should be managed through the study Investigator. If other therapies 
(e.g., medications, physical therapy) are being managed by another provider, it will be important 
for the study Investigator to be in contact with the patient’s provider throughout the study. 

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5. Study Visits 
Timing of visits and recommended visit windows are shown in Table 3. The visit windows are 
intended to provide guidance on timing of visits. A deviation will not be required if the visit is early 
or late, but will be required if the visit is missed. To avoid introduction of bias, all patient reported 
endpoint data will be collected before any other intervention or interview during the follow up visit. 
Programming the ReActiv8 and data collection via the Programmer will be performed by the 
Sponsor under Investigator direction and guidance. 
5.1. Informed Consent, Baseline Data, Inclusion Decision 
The process for obtaining informed consent shall comply with the Declaration of Helsinki, Good 
Clinical Practice (GCP) and IRB requirements. Patients will be provided with the Informed 
Consent Form which advises that data will be collected for evaluation of eligibility for inclusion in 
the study. If the patient agrees to inclusion for data collection, the Informed Consent will be signed 
and recorded in the patient’s records. The patient will then be assigned a unique study identifier. 
Data to be collected: 
• 
Screening data as required by the enrollment criteria 
• 
Treatment Plan Worksheet per the RESTORE Treatment Guidelines document (980016) 
• 
Medical History (including Physical Exam) 
o Baseline demographics 
o Comorbid conditions 
o Characteristics of the patient’s LBP such as diagnosis, duration, and number of 
episodes of LBP 
• 
Depression Anxiety Stress Scale (DASS21) 
• 
ODI 
• 
LBP NRS 
• 
EQ-5D 
• 
Leg pain description and NRS 
• 
Work status evaluation 
• 
Healthcare utilization 
• 
Pain treatments 
• 
Download activity monitoring data (if applicable) 
Activities to be performed: 
• 
Answer any questions the patient may have and confirm willingness to proceed if the 
baseline criteria are verified 
• 
Verify that the enrollment criteria are satisfied 
• 
An MRI of the lumbar region of the low back will be performed or ordered if there are no 
MRI images from more recently than 1 year prior to enrollment. If an MRI is being performed 
for the purposes of this study, please follow the recommended settings (Appendix 1). 
• 
MRI images will be reviewed to assess conditions that may be a possible cause of low back 
pain and to rule out possible surgical candidates by institutional guidelines 
• 
Multifidus dysfunction assessment (e.g., Prone Instability Test, Lift test) 
• 
Pregnancy test in women of child-bearing potential 
• 
Assessment by the Investigator of the patient’s suitability for ReActiv8 implant 

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5.1.1. 
Eligibility Assessment 
In addition to the Site Principal Investigator (PI) assessment of eligibility, an Independent MRI 
Assessment, and a Study PI Review will also be completed to determine eligibility. 
5.1.1.1. 
Independent MRI Assessment 
If the site determines that the patient is not excluded based on the MRI assessment, the site will 
upload images for further review. An appropriately trained independent physician will review the 
patient’s MRI to assess any current indication for back surgery according to appropriate evidence 
as summarized in the MRI Assessment Guidelines document (980017). 
5.1.1.2. 
Study Physician Advisor Review 
A Study Physician Advisor will review baseline data for all patients to confirm that the patient 
meets the eligibility criteria for the study. This review will take place prior to randomization and 
will be communicated to the Site PI and study staff. 
5.2. Randomization 
If the patient meets the enrollment criteria, the patient should be randomized approximately 14 
days after the baseline data have been collected. For those randomized to the Treatment group, 
schedule the surgery for the ReActiv8 implant. 
5.3. Implant Procedure (Treatment Group) 
The implant procedure should take place approximately 14 days following randomization. The 
implant procedure, including pre- and post-implant care, will follow the ReActiv8 Implant and 
Programming Manual (990070-001), and institutional guidelines. 
Data to be collected: 
• 
Device information (e.g., serial numbers, implant location, procedure duration) 
• 
Related AEs and all SAEs 
 
5.4. Activation (Treatment Group) 
Data to be collected: 
• 
Related AEs and all SAEs 
Activities to be performed: 
• 
Inspect surgical wound to verify healing and remove sutures (if not previously removed) 
• 
Perform electrode impedance and threshold measurements and program the IPG 
• 
Device download 
• 
Train in use of the Activator and document assessment of patient’s ability to self- 
administer therapy twice a day starting the next day 
• 
Train in the procedure to deliver stimulation, including time of day and positioning 
• 
Download activity monitoring data (if applicable) 

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5.5. 1.5-Month Visit 
Data to be collected: 
• 
ODI 
• 
LBP NRS 
• 
EQ-5D 
• 
Percent Pain Relief 
• 
SGIC 
• 
Treatment Satisfaction 
• 
Low back pain description 
• 
Leg Pain Description and NRS 
• 
Pain treatments 
• 
Related AEs and all SAEs 
• 
Download activity monitoring data (if applicable) 
For patients in the Treatment group only: 
• 
Remind patient to continue to lie down and activate therapy twice daily 
• 
Device download 
• 
Adjustment of stimulation configuration as appropriate 
 
5.6. 3- and 6-Month Visits 
Data to be collected: 
• 
ODI 
• 
LBP NRS 
• 
EQ-5D 
• 
Percent Pain Relief 
• 
SGIC 
• 
Treatment Satisfaction 
• 
Low back pain description 
• 
Leg Pain Description and NRS 
• 
Pain treatments 
• 
Related AEs and all SAEs 
• 
Download activity monitoring data (if applicable) 
For patients in the Treatment group only: 
• 
Remind patient to continue to lie down and activate therapy twice daily 
• 
Device download 
• 
Adjustment of stimulation configuration as appropriate 

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5.7. 1-Year, 18-Month and 2-Year Visits 
At the 1-year visit patients in the Control group may elect to receive ReActiv8 therapy. Schedule 
the surgery for the ReActiv8 implant and discuss with the patient. 
Data to be collected: 
• 
ODI 
• 
LBP NRS 
• 
EQ-5D 
• 
Percent Pain Relief 
• 
SGIC 
• 
Treatment Satisfaction 
• 
Low back pain description 
• 
Leg Pain Description and NRS 
• 
Health care utilization (not required at the 18-month visit) 
• 
Work Status Evaluation (not required at the 18-month visit) 
• 
Low Back Pain descriptive characteristics (not required at the 18-month visit) 
• 
Pain treatments 
• 
Related AEs and all SAEs 
• 
Download activity monitoring data (if applicable) 
For patients in the Treatment group only: 
• 
Device download 
• 
Adjustment of stimulation configuration as appropriate 
 
5.8. Implant (Control Group) 
The implant procedure, including pre- and post-implant care, will follow the ReActiv8 Implant and 
Programming Manual (990070-001), and institutional guidelines. 
Data to be collected: 
• 
Device information (e.g., serial numbers, implant location, procedure duration) 
• 
Related AEs and all SAEs 
 
5.9. Activation (Control Group) 
Data to be collected: 
• 
Related AEs and all SAEs 
Activities to be performed: 
• 
Inspect surgical wound to verify healing and remove sutures (if not previously removed). 
• 
Perform electrode impedance and threshold measurements and program the IPG 
• 
Device download 
• 
Train in use of the Activator and document assessment of patient’s ability to self- 
administer therapy twice a day starting the next day 
• 
Train in the procedure to deliver stimulation, including time of day and positioning 
• 
Download activity monitoring data (if applicable) 

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5.10. 13.5-Month and 15-Month Visits (Control Group) 
Data to be collected: 
• 
Pain treatments 
• 
Related AEs and all SAEs 
• 
Download activity monitoring data (if applicable) 
Activities to be performed: 
• 
Remind patient to continue to lie down and activate therapy twice daily. 
• 
Device download 
• 
Adjustment of stimulation configuration as appropriate 
 
5.11. Unscheduled Visits 
If an unscheduled visit occurs for any reason, collect all related AEs and all SAEs, update pain 
treatments, and download device information. 
5.12. Revision/Explant Procedure 
Data to be collected during or post revision/explant procedure: 
• 
Device information (e.g., serial numbers, implant location, procedure duration) 
• 
Related AEs and all SAEs 
Data to be collected after an explant procedure: 
• 
Related AEs and all SAEs will be collected over the last 30 days prior to exiting the study 
6. Anticipated Benefits and Risks 
6.1. Anticipated Benefits 
Although there are no guaranteed benefits, based on previous studies utilizing ReActiv8 therapy, 
the benefits from the stimulation to be delivered by the ReActiv8 may include decrease in low 
back pain, decrease in disability, and improvement in quality of life. As OMM is per standard of 
care, there are no additional benefits associated with OMM beyond those expected with standard 
of care. 
6.2. Anticipated Risks 
All medical device treatments have the potential to cause AEs or side effects. AEs are expected 
to be similar to other neurostimulation devices for treatment of back pain, such as spinal cord 
stimulators. Risks associated with OMM are the same as would be expected with standard of 
care. 
Additional information on risks and anticipated AEs may be found in the Implant and Programming 
Manual (990070-001), which also includes warnings and precautions. 

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6.3. Risk Minimization 
Additional risks may exist. Risks can be minimized through the use of strict compliance with this 
protocol, and adherence to the guidelines for patient selection, site training, and close monitoring 
of the patient’s physiologic status at follow-up visits. In addition, the product labeling (including 
the Implant and Programming Manual (990070-001) and the User Manual (990071-001)) details 
warnings and precautions which must be followed to minimize risk to patients. 
6.4. Patient Deaths 
A patient death during the study should be reported to the Sponsor as soon as possible. The 
clinical site’s IRB must be notified of any deaths in accordance with that clinical site’s IRB policies 
and procedures. 
7. Data Management 
The Sponsor will be responsible for collection of the data required for this study in accordance 
with Health Insurance Portability Accountability Act (HIPAA) and GCP. The Sponsor will use an 
electronic database which shall have written procedures and document requirements. Security, 
reliability, consistency of the data will be maintained throughout the study. Only those staff at each 
site that are identified and designated by the Investigator and trained will be allowed access to 
the database. Any questionnaires completed by the patient will be done electronically or on paper 
CRFs then transferred to the database by the designated study site personnel. 
7.1. Adverse Event Reporting 
The Investigator will monitor the occurrence of related AEs and all SAEs for each enrolled patient 
and will report them on the AE form. If a patient undergoes an explant procedure, the patient 
should remain in the study for at least 30 days post-explant to ensure that any AEs resulting from 
the procedure may be reported and addressed. 
All Related AEs, all SAEs, and all UADEs will be reported to all Investigators and IRBs 
participating in the study per their reporting requirements. Interim reports and a final study report 
prepared by the Sponsor will provide this information. 
7.2. Reporting of Device Deficiencies 
Device deficiencies will be reported through the Complaint Handling system. 
 
7.3. Management of Protocol Deviations 
An Investigator is required to conduct this study in accordance with this protocol and any IRB 
conditions of approval. All deviations from the protocol must be reported to the Sponsor together 
with the reason for the deviation and possible corrective actions for the deviations. In some 
circumstances, the clinical site may be required to notify the clinical site’s IRB. 

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Except in emergency situations, protocol deviations require prior Sponsor approval, and if the 
deviation may affect the scientific soundness of the plan or the rights, safety, or welfare of patients, 
prior IRB approval is required. 
An Investigator shall notify the Sponsor and the reviewing IRB of any deviation from the protocol 
to protect the life or physical well-being of a patient in an emergency. Such notice shall be given 
as soon as possible, but no later than five working days after the emergency occurred. 
7.4. Informed Consent 
Informed Consent is required from all patients (or their legal representatives) prior to the patient’s 
participation in the study. The process of obtaining Informed Consent shall comply with the 
Declaration of Helsinki, GCP, and IRB requirements. 
The process of obtaining informed consent shall: 
a) Avoid any coercion of or undue influence of patients to participate, 
b) Not waive or appear to waive patient’s legal rights, 
c) Use native language that is non-technical and understandable to the patient or his/her 
legal representative, 
d) Provide adequate time for the patient to consider participation and ask questions if 
necessary, 
e) Informed consent shall always be signed and personally dated by the patient or legal 
representative and by the Investigator or delegate. 
The original signed Informed Consent must be retained on file by the Investigator and a copy 
given to the patient (Investigator’s responsibility). 
7.5. Patient Data Confidentiality 
Throughout the study, confidentiality shall be maintained at all times, by all parties involved, and 
all data shall be secured against unauthorized access. Confidentiality of each patient shall be 
preserved in reports and any publication of the results. Only authorized personnel and their 
designees will have access to these confidential files. Patient data may be made available to 
regulatory agencies, under strict confidentiality condition. Source documents should be 
maintained at the clinical site. The clinical sites shall ensure that data (e.g., worksheets, 
programmer printouts, medical records, digital images, activity monitoring data) forwarded to the 
Sponsor do not contain any patient identifying data (such as name and birth date) other than the 
patient ID. 
All patients’ health information will be kept confidential in accordance with all applicable laws and 
regulations. Patients’ health information may be used to conduct this research, as well as for 
additional purposes, such as overseeing and improving the performance of products, new medical 
research and proposals for developing new medical products or procedures, and other business 
purposes. Patient personal information received during the study will not be used to market to 
patients; patient names will not be placed on any mailing lists or sold to anyone for marketing 
purposes. 

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7.6. Record Keeping 
Investigators are required to maintain on file the accurate, complete, and current records relating 
to this study: 
• All correspondence with another Investigator, an IRB, the Sponsor, or a monitor, including 
required reports 
• The signed protocol with any amendments 
• The approved template of the patient informed consent form 
• IRB approval of the protocol and any amendments and renewals 
• The Investigators’ agreement and the study agreement (separate or combined) 
• The Implant and Programming Manual (990070-001) User Manual (990071-001) and any 
other documentation provided with the device 
• Current curriculum vitae for the PI and all Sub-investigators 
• Monitoring letters (if applicable) 
• Interim/final reports 
• Study initiation forms 
• Study closure documents 
In addition, to the study administrative documents, patient records shall be appropriately filed, 
including the following: 
• Signed informed consent forms 
• Records of any related AE or any SAE, including supporting documentation 
• Records pertaining to patient deaths during the study 
• Relevant source data 
• Any other records required by the Sponsor 
8. Study Management 
8.1. Procedures to Amend the Protocol 
All amendments to the protocol shall be agreed upon by the Sponsor and the Investigators and 
be recorded with a justification for the amendments. In all cases of changes to the protocol, the 
local rules for approval of modifications shall be followed, including by way of example a 
submission to the IRB (either in full or to the Chairman), and modifications to the clinical study 
contract with the institution if applicable. 
8.2. Data Monitoring Plan 
It is the responsibility of the Sponsor to ensure proper monitoring of the study per GCP. 
Appropriately trained Sponsor personnel or delegates appointed by the Sponsor will perform 
study monitoring at the clinical site to ensure that the study is conducted in accordance with the 
protocol, the signed Clinical Study Agreement, and any IRB requirements. The Sponsor must 
therefore be allowed access to the patients’ clinic and hospital records when so requested as per 
the consent form, Privacy Authorization and Clinical Study Agreement. A separate Monitoring 
Plan will detail levels of source verification for this study. 

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8.3. Sponsor Responsibilities 
MML US Inc. (a subsidiary of Mainstay Medical Limited, Ireland) (“Mainstay”) is the Sponsor of 
this study, where a Sponsor is defined as an individual or organization taking the responsibility 
and liability for the intention or implementation of a clinical study. 
It is the responsibility of the Sponsor to ensure proper monitoring of the study and to see that all 
clinical requirements are met. 
Participation in the study will be limited to Sponsor personnel who are appropriately qualified and 
trained on the clinical study and on appropriate clinical study regulations and guidelines for 
medical device studies. It is the responsibility of the Sponsor to ensure appropriate training of all 
individuals involved in the clinical study. This includes Investigators and other health care 
professionals at the clinical sites, Sponsor personnel, and contractors, if applicable. 
8.4. Role of the Sponsor Representatives 
Sponsor personnel can provide technical support to the Investigator and other health care 
personnel as needed during implant, testing required by the protocol, and follow-up visits. Support 
may include training, addressing questions, or providing clarifications concerning the operation of 
Sponsor equipment (including programmers and other support equipment) or the procedures and 
forms related to the protocol. 
At the request of the Investigator and while under the Investigator’s supervision, Sponsor 
personnel may operate equipment during implant or follow-up visits, assist with the conduct of 
testing specified in the protocol, and interact with the patient to accomplish requested activities. 
Typical tasks may include: 
• Interrogating the device or programming device parameters to physician requested settings 
• Performing lead diagnostic testing using a programmer to obtain thresholds and impedance 
measurements 
• Clarifying device behavior, operation or diagnostic output as requested by the Investigator 
or other health care personnel 
• Assisting with the collection of study data from programmers and other equipment 
• Observing testing or medical procedures to provide information relevant to protocol 
compliance 
• Reviewing collected data and study documentation for completeness and accuracy 
At no point shall personnel from the Sponsor or CRO: 
• Practice medicine 
• Discuss with the patient the patient’s diagnosis or recommend treatment 
• Enter data into the database 
 
8.5. Clinical Investigators 
The Investigator is responsible for conducting the study in accordance with the protocol, the 
Declaration of Helsinki, the signed Investigator Agreement and other agreements, and any IRB 
conditions of approval. By agreeing to this protocol, the Investigators and their institutions accept 

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to allow monitoring and IRB review related to the study. They also agree to provide authorized 
individuals with access to source data and documentation as well as the right to copy records, 
provided such activities do not violate patient consent and patient data confidentiality. 
The Investigator is responsible for protecting the rights, safety, and welfare of patients under the 
Investigator’s care. The Investigator is also responsible for ensuring that informed consent is 
obtained in accordance with this protocol, GCPs, and IRB requirements. 
8.6. Investigator Selection 
The PI shall be: 
• Qualified by education, training and experience to assume responsibility for the proper 
conduct of the clinical study; evidence of such qualifications of the PI and key members of 
the clinical site team shall be provided to the Sponsor through up-to-date CVs, current GCP 
certification or other relevant documentation 
• Experienced in the field of application and trained in the use of the study device 
• Knowledgeable with the method of obtaining informed consent. 
A PI and any Sub-investigator(s) must be experienced in and responsible for the following: 
• Patient well-being 
• Strict adherence to the protocol, which includes all testing requirements to provide for 
optimal safe and efficacious use of the study device 
• Return of explanted devices, if applicable 
• Providing the patient with comprehensive information about the study and documenting 
patient consent and data during the study 
• Addressing medical questions which might be asked, either by the Sponsor or by the IRB, 
during or after the study 
• Ensuring that any related AE or any SAE is reported according to Section 7.1 
• Notifying the Sponsor of any deviation from the Protocol with an explanation for the deviation 
according to Section 7.3 
• Reporting patient deaths according to Section 6.4 
It is acceptable for the PI to delegate one or more of the above functions to an associate or Sub- 
investigator. However, the PI remains responsible for proper conduct of the study. The study is 
not transferable to other locations attended by the Investigator unless prior approval is obtained 
from the appropriate reviewing IRB and the Sponsor. 
8.7. Publication Policy 
Authorship of publications shall follow the recommendations of the International Committee of 
Medical Journal Editors1, which may result in employees of the Sponsor being included as 
authors. 
 
 
 
1 
http://www.icmje.org/ethical_1author.html 

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Should presentation or publication be contemplated, the Sponsor shall be provided with copies of 
any abstracts, papers or manuscripts for review and approval within a reasonable period prior to 
submittal for publication or presentation. The Sponsor shall limit its review to a determination of 
whether Confidential Information is disclosed and shall not attempt to censor or in any way 
interfere with the presentation or publication beyond the extent necessary to protect Confidential 
Information or to allow the Sponsor to protect its rights in patentable or copyrightable material. 
8.8. Payments and Costs to Patient 
The patient will not be charged for tests or procedures required only for the study, including the 
device and implant procedure. This includes the device and procedure for the Control group after 
the 1-year timepoint if they elect to receive the device at that time. The Sponsor will reimburse 
the clinical site and/or Investigator for their fair costs for the tests and procedures required for the 
study. 
The Sponsor will not pay the patient or anyone else for any other medical costs (e.g., 
prescriptions, other therapies) related to the patient’s participation in the study. 
Patients will be reimbursed for reasonable transportation costs according to local institutional 
guidelines of up to $550 in any calendar year. 
8.9. Maintaining Compliance 
The study will be conducted according to GCP and the Declaration of Helsinki. 
 
8.9.1. 
Study Monitoring 
Monitoring will be performed during the study to ensure that compliance with the protocol and IRB 
requirements, and that data are collected in a timely, accurate and complete manner, and that 
the Investigator continues to have sufficient staff and facilities to conduct the study safely and 
effectively. 
Monitors are individuals who are designated to oversee the progress of a study. These individuals 
are appropriately trained and qualified to monitor the progress of a study. Monitors will be selected 
and assigned by the Sponsor. 
8.9.2. 
Review of Submitted Data 
In addition to the site monitoring visits the data submitted by the clinical site will be reviewed for 
completeness and accuracy. The clinical site personnel will be contacted regarding any missing 
or unclear data. 
8.10. Study Completion 
The Sponsor will notify each Investigator of the completion or termination of the study or of the 
Investigator's participation in the study. At the Sponsor’s request, an Investigator will return any 
devices in his or her possession. The Investigator will provide a summary to the Sponsor and 
reviewing IRB of their data. 

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8.11. Suspension or Premature Termination of the Study 
The procedure to be followed as a result of suspension or premature termination of the study shall 
be in compliance with the Sponsor’s SOPs. 
If suspension or premature termination occurs, the terminating party shall justify its decision in 
writing and promptly inform the other parties with whom they are in direct communication. The PI 
and Sponsor shall keep each other informed of any communication received from the IRB. 
If the Sponsor decides to discontinue the study for any reason, the Sponsor will promptly inform 
all Investigators and IRBs along with detailed information on how enrolled patients should be 
managed thereafter. All patients enrolled in the study will continue to be followed according to the 
protocol unless the Sponsor notifies the clinical sites otherwise. 
An Investigator may also discontinue participation in the study with suitable written notice to the 
Sponsor. Should either of these events occur, the Investigator shall: 
• Return all documents and devices to the Sponsor 
• Provide a written statement as to why the premature termination has taken place 
• Notify the IRB 
If suspension or premature termination occurs, the Sponsor shall remain responsible for providing 
resources to fulfill the obligations from the protocol and existing agreements for following up the 
patients enrolled in the clinical study, and the PI or authorized designee shall promptly inform the 
enrolled patients at his/her clinical site, if appropriate. 

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9. Administrative Data 
9.1. Name and Address of the Sponsor 
MML US Inc. 
2159 India Street, Suite 200 
San Diego, CA 92101 
MML US Inc. is a subsidiary of 
Mainstay Medical Limited 
Clonmel House 
Swords, K67F2K3 
County Dublin, 
Ireland 
Sponsor’s Contact: 
Mainstay Medical Clinical Management 
 
9.2. Investigators 
Each clinical site shall have a Site PI. Subject to Sponsor approval, a Site PI shall delegate some 
or all of the patient interaction and data collection to one or more Sub-investigators or Study 
Coordinators. 
9.3. Statements of Compliance 
This clinical study shall be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki. 
The clinical study shall not begin until the required approval or favorable opinion from the IRB. 
Any additional requirements imposed by the IRB shall be followed. 

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Document Number 980012, Rev. D 
11-JAN-2024 
 
 
Appendix 1: MRI Recommended Protocol 
If an MRI is being performed for the purposes of this study, please make every effort to follow the 
recommended settings as noted below. 
General: 
• 
Sagittal imaging must extend through the facet joints into distal transverse processes. 
• 
All axial imaging should be contained within one sequence. If the images need to be 
angled, please angle within a single axial set of images as opposed to generating multiple 
axial sets with different angles, preferrable perpendicular to spinal canal at L4. 
• 
Scanner preference is standard configuration 1.5T or 3T (Preferred), not open MRI. 
• 
Axial 3D T2 is preferred (SPACE, VISTA, CUBE) with isotropic 1.0mm3 voxels, 
otherwise 2D axial slices. 
Coverage: 
• 
Sagittal images from T11-T12 through S2-S3. 
• 
Axial imaging should cover at a minimum L1 to S1, out to the iliac crests, and posterior 
adipose tissues to obtain all paraspinal muscles in the image. 
 
Plane 
Weighting 
Slice 
Gap 
Fat Sat 
Notes 
SAG 
T2 
5mm 
1mm 
None 
Through to distal transverse processes, 
T12-S2 min 
Axial 3D 
T2 
1mm3 
ISOTROPIC 
None 
Through to Iliac to cover paraspinal 
muscles, cover L1-L5 disc spaces, 
posterior to adipose tissue, continuous 
slices, perpendicular to canal at L4 if 
necessary. 3D T2 preferred at 1.0mm2 
(SPACE, VISTA, CUBE, etc). 
Axial 2D 
(only if 
3D not 
available) 
T2 
4mm 
0.5mm 
None 
Through to Iliac to cover paraspinal 
muscles, cover L1-L5 disc spaces, 
posterior to adipose tissue, continuous 
slices, perpendicular to canal at L4 if 
necessary. 
SAG 
T1 
5mm 
1mm 
None 
Through to distal transverse processes, 
T12-S2 min 
SAG 
STIR 
5mm 
1mm 
STIR 
Through to distal transverse processes, 
T12-S2 min 

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Page 42 of 47 
Document Number 980012, Rev. D 
11-JAN-2024 
 
 
 
 
 
 
MRI Order Notes: 
• 
Standard configuration 1.5T or 3T (Preferred) scanner, not open MRI. 
• 
If the images need to be angled, please angle within a single axial set of images as 
opposed to generating multiple axial sets with different angles, preferrable perpendicular 
to spinal canal at L4. 
Image Sets: 
• 
T2 SAG, 5mm Slice 1mm gap, FOV through to distal transverse processes, T12-S2 min 
• 
T2 Axial 3D (SPACE, VISTA, CUBE, etc), 1mm3 ISOTROPIC, FOV through to Iliac, L1- 
S1 minimum, posterior to adipose tissue to cover paraspinal muscles, perpendicular to 
canal at L4 if necessary. 
• 
IF NO 3D: T2 Axial 2D, 4mm Slice 0.5mm Gap. Continuous slices. FOV through to Iliac, 
L1-S1 minimum, posterior to adipose tissue to cover paraspinal muscles, perpendicular 
to canal at L4 if necessary. 
• 
T1 SAG, 5mm Slice 1mm gap, FOV through to distal transverse processes, T12-S2 min 
• 
STIR SAG, 5mm Slice 1mm gap, FOV through to distal transverse processes, T12-S2 
min 

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Page 43 of 47 
Document Number 980012, Rev. D 
11-JAN-2024 
 
 
Appendix 2: Acronyms 
ACP 
American College of Physicians 
AE 
Adverse Event 
AMI 
Arthrogenic Muscle Inhibition 
APS 
American Pain Society 
BMI 
Body Mass Index 
CLBP 
Chronic Low Back Pain 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CV 
Curriculum vitae 
DASS  Depression Anxiety and Stress Scale 
EQ-5D European Quality of Life Assessment 
FBSS   Failed Back Surgery Syndrome 
FDA 
Food and Drug Administration 
FOV 
Field of View 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability Accountability Act 
ICMJE 
International Committee of Medical Journal Editors 
IPG 
Implantable Pulse Generator 
IRB 
Institutional Review Board 
LBP 
Low Back Pain 
MCID 
Minimal Clinical Important Difference 
MIC 
Minimally Important Change 
MRI 
Magnetic Resonance Imaging 
NICE 
The National Institute for Health and Care Excellence 
NRS 
Numerical Rating Scale 
NSLBP 
Non-Specific Low Back Pain 
ODI 
Oswestry Disability Index 
OMM 
Optimal Medical Management 
OUD 
Opioid Use Disorder 
PI 
Principal Investigator 
PMA 
Pre-Market Approval 
PPR 
Percent Pain Relief 
QOL 
Quality of Life 
SAE 
Serious Adverse Event 
SAG 
Sagittal 
SCS 
Spinal Cord Stimulation 
SGIC Subject Global Impression of Change 
STIR   Short-IT Inversion Recovery 
TENS 
Transcutaneous Electrical Nerve Stimulation 
UADE 
Unanticipated Adverse Device Effect 
US 
United States 

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Document Number 980012, Rev. D 
11-JAN-2024 
 
 
Appendix 3: Bibliography 
 
 
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3  Reuben, D.B., Alvanzo, A.A., Ashikaga, T., et al. National Institutes of Health Pathways to Prevention Workshop: the role of 
opioids in the treatment of chronic pain. Ann Intern Med. 162(4):295-300 (2015). 
4  Waljee, J.F.,Brummett, C.M. Opioid Prescribing for Low Back Pain: What Is the Role of Payers? JAMA Netw Open. 
1(2):e180236. doi:10.1001/jamanetworkopen.2018.0236 (2018). 
5  Lin DH, Jones CM, Compton WM, et al. Prescription Drug Coverage for Treatment of Low Back Pain Among US Medicaid, 
Medicare Advantage, and Commercial Insurers. JAMA Netw Open.1(2):e180235. doi:10.1001/jamanetworkopen.2018.0235 
(2018). 
6  Woolf, A. D., Pfleger, B. Burden of major musculoskeletal conditions. Bull. World Health Organ. 81, 646-56 (2003). 
7  Mehra M, Hill K, Nicholl D, Schadrack J: The burden of chronic low back pain with and without a neuropathic component: a 
healthcare resource use and cost analysis. J Med Econ. 15: 245-252 (2011). 
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(2006). 
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Treatment of Chronic Pain. https://doi.org/10.23970/AHRQEPCERTA218 (2014). 
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24 Cohen, S. P., et al. Effectiveness of Lumbar Facet Joint Blocks and Predictive Value before Radiofrequency Denervation: The 
Facet Treatment Study (FACTS), a Randomized, Controlled Clinical Trial. Anesthesiology 129(3): 517-535 (2018). 

RESTORE Clinical Protocol 
The contents of this document are confidential and are not to be reproduced or made available to third parties without prior consent 
from Mainstay Medical and are not to be used in any unauthorized way. 
Page 45 of 47 
Document Number 980012, Rev. D 
11-JAN-2024 
 
 
 
 
 
25 Juch, J. N. S., et al. Effect of Radiofrequency Denervation on Pain Intensity Among Patients with Chronic Low Back Pain: The 
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The contents of this document are confidential and are not to be reproduced or made available to third parties without prior consent 
from Mainstay Medical and are not to be used in any unauthorized way. 
Page 46 of 47 
Document Number 980012, Rev. D 
11-JAN-2024 
 
 
 
 
 
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from http://www.ncbi.nlm.nih.gov/pubmed/25879124 (2015). 
59 Chou, R., Huffman, L. H. Annals of Internal Medicine Clinical Guidelines Medications for Acute and Chronic Low Back Pain: A 
Review of the Evidence for an American Pain Society / American College of Physicians Clinical Practice Guideline. Annals of 
Internal Medicine (2007a). 
60 Chou, R., Huffman, L. H. Clinical Guidelines Annals of Internal Medicine Nonpharmacologic Therapies for Acute and Chronic 
Low Back Pain: A Review of the Evidence for an American Pain Society / American College of Physicians Clinical Practice 
Guideline. Annals of Internal Medicine (2007b). 
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Facet Treatment Study (FACTS), a Randomized, Controlled Clinical Trial. Anesthesiology 129(3): 517-535 (2018). 
62 Juch, J. N. S., et al. Effect of Radiofrequency Denervation on Pain Intensity Among Patients with Chronic Low Back Pain: The 
Mint Randomized Clinical Trials. JAMA 318(1): 68-81 (2017). 
63 Chou, R., Deyo, R., Friedly, J., Skelly, A., Weimer, M., Fu, R., et al. Systemic pharmacologic therapies for low back pain: A 
systematic review for an American College of physicians clinical practice guideline. Ann Intern Med.;166(7):480-92 (2017). 
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70 Waljee, J.F.,Brummett, C.M. Opioid Prescribing for Low Back Pain: What Is the Role of Payers? JAMA Netw Open. 
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71 Lin DH, Jones CM, Compton WM, et al. Prescription Drug Coverage for Treatment of Low Back Pain Among US Medicaid, 
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(2018). 
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74 Katz JN: Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J Bone Joint Surg. 88: 21-24 
(2006). 

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from Mainstay Medical and are not to be used in any unauthorized way. 
Page 47 of 47 
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11-JAN-2024 
 
 
 
 
 
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97 Chou, R., Deyo, R., Devine, B., Hansen, R., Sullivan, S., Jarvik, J. G., et al. The Effectiveness and Risks of Long-Term Opioid 
Treatment of Chronic Pain. https://doi.org/10.23970/AHRQEPCERTA218 (2014). 
98 Busse, J. W., et al. "Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis." JAMA 320(23): 2448-2460 
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