INTRACEPT: A Prospective, Randomized, Multi-Center Study of Intraosseous Basivertebral Nerve Ablation for the Treatment of Chronic Low Back Pain
Phase: NA
Conditions: Chronic Low Back Pain
Sponsor: Relievant Medsystems, Inc.

Relievant Medsystems 
 
INTRACEPT CIP 0006, Rev E 
 
Page 1 of 65 
CONFIDENTIAL AND PROPRIETARY 
October 17, 2018 
 
 
 
Title: 
INTRACEPT: A Prospective, Randomized, Multi-Center 
Study of Intraosseous Basivertebral Nerve Ablation for 
the Treatment of Chronic Low Back Pain 
Protocol Number: 
CIP 0006, REV E 
 
Device: 
INTRACEPT® INTRAOSSEOUS NERVE ABLATION SYSTEM 
 
Regulatory Status: 
 
The device has FDA 510(k) clearance in the US and is CE 
marked in the EU for its intended purpose as defined in the 
Instructions for Use 
 
 
Sponsor: 
Relievant Medsystems 
385 Moffett Park Drive, Suite 105 
Sunnyvale, CA 94089 
Date: 
OCTOBER 17, 2018 
 
 
 
 
CONFIDENTIAL 
This document contains confidential information.  It is intended solely for the recipient and must not be 
disclosed to any other party.  The material may be used only for evaluating or conducting clinical 
investigations; any other proposed use requires Sponsor written consent. 
 
 
 
 
 

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TABLE OF CONTENTS 
 
TABLE OF CONTENTS ............................................................................................................. 2 
1.0 
SYNOPSIS ................................................................................................................... 6 
2.0 
LIST OF ABBREVIATIONS ........................................................................................... 11 
3.0 
BACKGROUND .......................................................................................................... 12 
3.1 
Causes of Low Back Pain................................................................................................... 12 
3.2 
Epidemiology of Chronic Low Back Pain ............................................................................ 13 
3.3 
The Differential Diagnosis of Chronic Lower Back Pain ...................................................... 13 
3.4 
Pathophysiology of Vertebrogenic Back Pain .................................................................... 15 
3.4.1 
Discogenic versus Vertebrogenic Back Pain .......................................................................... 16 
3.5 
Treatments for Chronic Lower Back Pain ........................................................................... 17 
3.6 
Non-surgical Treatments for Lower Back Pain ................................................................... 18 
3.6.1 
Education............................................................................................................................... 18 
3.6.2 
Analgesics .............................................................................................................................. 18 
3.6.3 
Exercise.................................................................................................................................. 18 
3.6.4 
Physical Treatments .............................................................................................................. 18 
3.6.5 
Spinal Manipulative Therapy ................................................................................................. 19 
3.6.6 
Needle Acupuncture ............................................................................................................. 19 
3.6.7 
Multidisciplinary Rehabilitation ............................................................................................ 20 
3.6.8 
Injections and Nerve Treatments .......................................................................................... 20 
3.7 
Surgical Treatments for Chronic Lower Back Pain .............................................................. 20 
3.7.1 
Intradiscal Procedures ........................................................................................................... 20 
3.7.2 
Fusion Surgery ....................................................................................................................... 21 
3.7.3 
Total Disc Arthroplasty .......................................................................................................... 22 
3.8 
RF Ablation of the BVN for Treatment of Vertebrogenic Back Pain .................................... 22 
3.9 
Clinical Experience to Date ............................................................................................... 23 
3.9.1 
Feasibility Study .................................................................................................................... 23 
3.9.2 
Pivotal Clinical Trial – the SMART Study................................................................................ 23 
4.0 
DEVICE DESCRIPTION ................................................................................................ 24 
4.1 
The Intracept® Intraosseous Nerve Ablation System (Intracept System) ............................. 24 
5.0 
STUDY PROTOCOL .................................................................................................... 26 
5.1 
Study Objectives .............................................................................................................. 26 
5.1.1 
Primary Objectives ................................................................................................................ 26 
5.1.2 
Secondary Objectives ............................................................................................................ 26 
5.2 
Study Design .................................................................................................................... 26 
5.3 
Number of Sites ............................................................................................................... 27 
5.4 
Number of Subjects.......................................................................................................... 27 
5.5 
Study Duration................................................................................................................. 27 
5.6 
Study Population ............................................................................................................. 27 
5.7 
Subject Selection Criteria ................................................................................................. 27 
5.7.1 
Inclusion Criteria ................................................................................................................... 27 
5.7.2 
Exclusion Criteria ................................................................................................................... 28 
5.8 
Treatment Plan ................................................................................................................ 30 
5.8.1 
Screening ............................................................................................................................... 30 

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5.8.2 
Enrollment Monitor .............................................................................................................. 30 
5.8.3 
Baseline Assessments ............................................................................................................ 30 
5.8.4 
Randomization ...................................................................................................................... 31 
5.8.5 
Choosing the Target Vertebral Bodies .................................................................................. 31 
5.8.6 
Procedure for RF Ablation of the BVN using the Intracept System ...................................... 31 
5.9 
Schedule of Assessments.................................................................................................. 33 
5.10 
Crossover......................................................................................................................... 36 
5.11 
Study Exit ........................................................................................................................ 36 
5.12 
Study Withdrawal/Termination ........................................................................................ 36 
6.0 
STUDY ASSESSMENTS AND OUTCOME MEASURES .................................................... 37 
6.1 
Medical History ................................................................................................................ 37 
6.2 
Laboratory Tests .............................................................................................................. 37 
6.3 
Beck Depression Inventory (BDI-II) ................................................................................... 37 
6.4 
Imaging ........................................................................................................................... 38 
6.5 
Neurologic and Physical (Orthopedic) Exam ...................................................................... 39 
6.6 
Oswestry Disability Index (ODI) ........................................................................................ 39 
6.7 
Visual Analogue Scale (VAS) ............................................................................................. 39 
6.8 
Short Form-36 Instrument (SF-36) .................................................................................... 39 
6.9 
EuroQOL Quality of Life Instrument (EQ-5D-5L) ................................................................. 39 
6.10 
Patient Satisfaction .......................................................................................................... 40 
6.11 
Concomitant Back Pain Medications ................................................................................. 40 
6.12 
Concomitant Therapy ....................................................................................................... 40 
6.13 
Adverse Events ................................................................................................................ 40 
7.0 
ASSESSMENT OF EFFICACY ........................................................................................ 44 
7.1 
Primary Efficacy Endpoint ................................................................................................ 44 
7.2 
Secondary Efficacy Endpoints ........................................................................................... 44 
7.3 
Long-term Surveillance Endpoints .................................................................................... 45 
7.4 
Additional Outcomes of Interest ....................................................................................... 45 
8.0 
ASSESSMENT OF SAFETY ........................................................................................... 46 
8.1 
Safety Endpoints .............................................................................................................. 46 
9.0 
DATA ANALYSIS AND STATISTICAL METHODS ........................................................... 46 
9.1 
Determination of Sample Size .......................................................................................... 46 
9.2 
Analysis Populations ........................................................................................................ 46 
9.3 
Demographic and Baseline Characteristics ........................................................................ 47 
9.4 
Primary Efficacy Analysis .................................................................................................. 47 
9.5 
Interim Analysis ............................................................................................................... 48 
9.5.1 
Interim Analysis 1 .................................................................................................................. 48 
9.5.2 
Interim Analysis 2 .................................................................................................................. 48 
9.6 
Secondary Efficacy Analyses ............................................................................................. 48 
9.6.1 
ODI ......................................................................................................................................... 48 
9.6.2 
VAS ........................................................................................................................................ 48 
9.6.3 
SF-36 ...................................................................................................................................... 49 
9.6.4 
EQ-5D-5L ............................................................................................................................... 49 
9.6.5 
Patient Satisfaction ............................................................................................................... 49 
9.6.6 
Targeting Success .................................................................................................................. 49 
9.7 
Long-Term Surveillance Endpoint Analyses ....................................................................... 50 

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9.8 
Analysis of Additional Outcomes of Interest ..................................................................... 50 
9.8.1 
Health-related Quality of Life and Disability ......................................................................... 50 
9.8.2 
Costs ...................................................................................................................................... 50 
9.8.3 
Quality-Adjusted Life Years ................................................................................................... 51 
9.8.4 
Analyses ................................................................................................................................. 51 
9.9 
Safety Endpoint Analyses ................................................................................................. 51 
10.0 
SUBJECT BENEFIT AND RISKS .................................................................................... 51 
10.1 
Risks of the Intracept System ........................................................................................... 51 
10.2 
Mitigation of Risk ............................................................................................................. 53 
10.3 
Risk-Benefit Analysis ........................................................................................................ 53 
11.0 
STUDY OPERATIONS AND EVALUATIONS .................................................................. 53 
11.1 
Reporting and Recording of Data ...................................................................................... 53 
12.0 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL .......................................... 54 
12.1 
Investigator Qualifications ............................................................................................... 54 
12.2 
Study Initiation ................................................................................................................ 54 
12.3 
Informed Consent ............................................................................................................ 55 
12.4 
Amendments and Deviations ........................................................................................... 55 
12.4.1 Protocol Amendments .......................................................................................................... 55 
12.4.2 Protocol Deviations ............................................................................................................... 55 
12.5 
Institutional Review Board (IRB) Approval ........................................................................ 55 
12.6 
Regulatory Compliance .................................................................................................... 55 
12.7 
Study Monitoring Requirements ....................................................................................... 55 
12.8 
Case Report Forms ........................................................................................................... 56 
12.9 
Data Management ........................................................................................................... 56 
12.10 
Disclosure of Data ........................................................................................................ 56 
12.11 
Retention of Records ................................................................................................... 56 
12.12 
Data Quality Assurance ................................................................................................ 57 
13.0 
Appendix 1: Investigator Signature Page ................................................................... 58 
14.0 
Appendix 2: Main Study Schedule of Assessments .................................................... 59 
15.0 
Appendix 3: Sub Study Additional Follow-Up Schedule of Assessments ..................... 60 
16.0 
References ............................................................................................................... 61 
 
 
 
 
 
 
LIST OF TABLES 
Table 1:  Brief Description of Intracept System ......................................................................................... 25 
Table 2:  RF Ablation Parameters. .............................................................................................................. 32 
Table 3:  Categories of AEs ........................................................................................................................ 41 

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Table 4: Severity of Adverse Events ........................................................................................................... 43 
 
 
LIST OF FIGURES 
Figure 1:  Illustration of the BVN (red) ................................................................................................ 16 
Figure 2:  The Intracept System ............................................................................................................ 25 
Figure 3: VB access and Positioning at the Basivertebral Foramen ..................................................... 32 
Figure 4:  Main Study Schematic .......................................................................................................... 35 
 
 
 
 
 

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1.0 SYNOPSIS 
Protocol Title: 
A Prospective, Randomized, Multi-center Study of Intraosseous Basivertebral Nerve 
Ablation for the Treatment of Chronic Low Back Pain 
Protocol 
Number: 
CIP 0006, Rev E 
Sponsor: 
Relievant Medsystems, Inc. 
Objectives 
The primary efficacy endpoint is the mean change from baseline to 3 months post-
treatment in the Oswestry Disability Index (ODI). The primary endpoint will be evaluated 
in both the treatment and control groups with between-group comparisons used to assess 
the success of the Intracept System in reducing chronic axial low back pain. 
Indication/ 
Population 
The Intracept® Intraosseous Nerve Ablation System is intended to be used in conjunction 
with radiofrequency (RF) generators for the ablation of basivertebral nerves of the L3 
through S1 vertebrae for the relief of chronic low back pain of at least 6 months’ duration 
that has not responded to at least 6 months of conservative care, and is also accompanied 
by either Type 1 or Type 2 Modic changes on magnetic resonance imaging (MRI). 
Study Design 
This is a prospective, randomized, multi-center, controlled study with an optional 
crossover component. 
Subjects will be randomized 1:1 RF ablation arm vs Control arm; this is an open-label trial.  
Subjects in the RF ablation arm will receive the Intracept System procedure to treat one or 
two motion segments at L3/L4, L4/L5, or L5/S1 as identified by Modic type 1 or 2 
changes.  Subjects in the Control arm will continue non-surgical management therapies to 
treat their CLBP and will be offered optional crossover after 12 months of follow-up. 
Number of 
Subjects 
150 randomized and treated subjects.  Approximately 600 subjects will be screened to 
achieve 150 enrolled (randomized) subjects [based on assumption of 75% screen failure 
rate]. 
Number of Sites 
Between 10 and 25 US sites. 
Duration of 
Participation 
Subjects in the RF Ablation arm will be followed for 24 Months following treatment. 
Control arm subjects will be offered optional crossover treatment after the 12-month 
follow-up visit and will then be followed for an additional 6 months following crossover.   
It is estimated that this study may take up to 2 years to enroll, therefore from first subject 
consented through last subject 12-month visit, this study will take approximately 42 
months for completion of all 12-month follow-up.  The subjects in the RF Ablation arm 
will take an additional 6 months to complete the 24-month follow-up. 
Primary 
Efficacy 
Endpoint 
The primary efficacy variable is the Oswestry Disability Index (ODI) and the primary 
efficacy endpoint is the mean change from baseline to 3 months post-treatment in the ODI. 
The primary efficacy endpoint will be evaluated in both the treatment and control groups 
with between-group comparisons used to assess the success of the Intracept System in 
reducing chronic axial low back pain. 
 
 

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Secondary 
Efficacy 
Endpoints 
• 
ODI 
o 
The mean change in disability from Baseline to 6, 9 and 12 months, as 
measured by the ODI. 
o 
The percentage of subjects who have ≥ 10-point reduction in ODI from 
Baseline to 3 months post-treatment 
• 
Visual Analog Scale (VAS) 
o 
The mean change in pain from Baseline to 3, 6, 9 and 12 months, as 
measured by VAS 
o 
The percentage of subjects who have ≥ 1.5 cm reduction in VAS from 
Baseline to 3 months post-treatment 
• 
The mean change in the SF-36 Physical Component Summary (PCS) and Mental 
Component Summary (MC) scores from Baseline to 3, 6, 9 and 12 months  
• 
The mean change in quality of life from Baseline to 3, 6, 9 and 12 months, as 
measured by the EQ-5D-5L index. 
• 
Mean satisfaction ratings at 3, 6, 9 and 12 months, as measured on satisfaction rating 
scales. 
• 
The percentage of subjects who have radiographic evidence of targeting success based 
on lesion location on MRI. 
Long-term 
Surveillance 
Endpoints 
Subjects in the RF Ablation arm only will return for additional long-term surveillance 
follow-up at 24 months post-treatment.  Evaluations to be performed will include the mean 
change from Baseline to 24 months post-treatment, as measured by the ODI, VAS, SF-36, 
and EQ-5D-5L, as well as the Patient Satisfaction rating. At the 24-month visit, RF 
Ablation subjects will be approached to participate in a sub-study entailing five years of 
post-procedure (additional study visits at 36, 48, and 60 months).   
Additional 
Outcomes of 
Interest 
• 
Additional analyses of health-related quality of life and disability associated with back 
pain at baseline, 3, 6, 9, and 12 months as estimated via the EQ-5D-5L, SF-36, and ODI 
questionnaires.   
• 
Resource utilization and related costs associated with back pain at baseline, 3, 6, 9 and 
12 months, as estimated via treatment procedures, back pain medication usage, and 
national database statistics. 
• 
Quality of Life Years (QALY) gain for RF ablation arm and control arm, determined 
based on EQ-5D-5L data and mortality, and difference between the two strategies at 
various follow-up time points. 
• 
Incremental cost-effectiveness based on costs and QALYs for RF ablation vs. control 
arm. 
Safety 
Endpoints 
• 
The cumulative incidence and severity of device, procedure, neurological and spine 
related adverse events from the treatment procedure through the final follow-up visit.  
Deterioration of neurological status will be recorded as an AE (defined as a 1-grade or 
more deficit in any motor or dermatomal sensory group). 
• 
The cumulative incidence of device, procedure, or spine-related SAEs and Significant 
neurological events (defined as a 2-grade or more deficit in any motor or dermatomal 
sensory group) from the treatment procedure through the final follow-up visit.   
 
 

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Inclusion/ 
Exclusion 
Criteria 
Inclusion Criteria: 
1) Skeletally mature subjects age 25 – 70 years, inclusive 
2) Chronic lower back pain for at least six (6) months  
3) Failure to respond to at least six (6) months of non-operative conservative 
management.   
4) Oswestry Disability Index (ODI) at time of evaluation of at least 30 points 
5) Baseline Visual Analog Scale (VAS) of at least 4 cm on a 10 cm scale 
6) Modic changes (Type 1 or 2) in at least one vertebral endplate, at one or more levels 
from L3 to S1 
7) Fluent in reading, writing, speaking, and understanding the English language, and is 
willing and able to follow the requirements of the protocol, including the post-operative 
management program and follow-up schedule 
8) Understands the informed consent and signs the institutional review board (IRB) 
approved informed consent form 
 
Exclusion Criteria: 
1) Radicular pain by history or evidence of pain or neurological deficit within the past 
one year. Radicular pain is defined as nerve pain following a dermatomal distribution 
and that correlates with nerve compression on imaging. Somatic referred pain is 
allowed.  
2) Previous surgery performed on the lumbar spine  
i) 
Note: previous lumbar decompression not affecting spinal stability or 
mechanics is allowed (unilateral or bilateral laminotomy or 
laminoforaminotomy) if procedure was more than six-months prior to 
screening date and all radicular pain has resolved 
3) Current or history of symptomatic spinal stenosis 
4) Current or history of osteoporotic or tumor-related vertebral body compression 
fracture 
5) Current or history of vertebral cancer or spinal metastasis 
6) Current or history of spinal infection  
7) Metabolic bone disease (e.g. osteogenesis imperfecta) 
8) BMI ≥40 (without rounding) unless there is documentation that obesity is not a 
primary contributing factor for the potential subject’s CLBP (i.e. muscularly dense 
subject with vertebrogenic pain). 
9) History of a fragility fracture (fracture following a low energy injury-vertebral 
compression, hip, wrist, pelvis, etc.) or current treatment with prescription medications 
for osteopenia. 
10) Any radiographic evidence of other important back pathology, such as: 
a) Nerve root compression, neurogenic claudication, or severe effacement of the 
thecal sac that correlates with radicular pain or muscle weakness  
b) Disc extrusion or disc protrusion >5mm  
c) Facet arthrosis or facet effusion at any lumbar level that correlates with clinical 
evidence of facet mediated low back pain 
d) Spondylolisthesis 2 mm or greater at any level 
e) Spondylolysis at any level 
11) MRI evidence of Modic changes, Type I or Type II at vertebral bodies other than L3 to 
S1. 
12)  Any back pathology related to trauma, evidence of vertebral compression fracture or 
other spinal pathology that could affect assessment of response to back pain 
13) Subjects who are bed bound 
14) Demonstrates 3 or more Waddell’s signs of Inorganic Behavior 
15) Any evidence of current systemic infection 
16) Uncorrected bleeding diathesis 
17) Any neurologic problem that prevents early mobilization after surgery or interferes 
with assessment of ODI 

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18) Contraindication to MRI or subjects who have allergies to the components of the 
Intracept device specifically nitinol, PEEK (Poly Ether Ether Ketone), stainless steel, 
or PEBAX (Poly Ether Block Amide) 
19) Pregnant, lactating or plan to become pregnant in next year 
20) Evidence of mental instability or uncontrolled depression; subjects requiring new or 
any change in anti-depressants or anti-psychotic medications within 3 months of 
enrollment; subjects with a Beck Depression Score of greater than 24 
21) Compensated injuries or ongoing litigation regarding back pain/injury, or financial or 
other incentive to remain impaired 
22) Any medical condition that impairs follow-up (i.e. fibromyalgia, rheumatoid arthritis, 
chronic regional pain syndrome, reflex sympathetic dystrophy) 
23) Contraindications to the proposed anesthetic protocol. 
24) Evidence of substance abuse; subjects using prescribed extended release narcotics (e.g. 
fentanyl patch, MS contin, oxycontin) within the 3 months prior to screening and who 
are motivated to remain impaired for continued prescribing of extended release 
narcotics.  
25) Known, at the time of screening and/or randomization, to require additional surgery to 
the lumbar spinal region within six months 
26) History of SI joint fusion within the past two years 
27) Being treated with radiation, chemotherapy, immunosuppression, or chronic steroid 
therapy (prednisone, or its equivalent, use of up to 5 mg/qd is allowed, as well as 
inhalation steroids for asthma) 
28) Has a life expectancy of less than 2 years 
29) Has active implantable devices, such as cardiac pacemakers, spinal cord stimulators, 
etc. 
Treatment and 
Follow-up 
Schedule 
• 
Screening Visit (may be completed over more than one study visit):  Written informed 
consent.  Collection of demographic information.  Pregnancy test. Completion of BDI 
questionnaire.  Review of medical history.  Physical and neurological examination.  
MR imaging and standing lateral x-ray.  Review of densitometry if available.  Review 
of inclusion/exclusion criteria.  Completion of questionnaires (ODI, VAS). LBP 
concomitant medications and therapies 
• 
Baseline Visit:  Physical and neurological examination. Pregnancy test. Completion of 
questionnaires (ODI, VAS, SF-36, EQ-5D-5L). LBP concomitant medications and 
therapies. 
• 
Randomization and Treatment with Intracept System or assignment to Control arm 
• 
6 Weeks Post-Treatment:  MR imaging.  (RF Ablation arm and crossover subjects 
only) 
• 
3 Month Follow-up:  Physical and neurological exam, completion of questionnaires, 
assessment of adverse events, LBP concomitant medications and therapies. 
• 
6 Month Follow-up: Physical and neurological exam, completion of questionnaires, 
assessment of adverse events, LBP concomitant medications and therapies. 
• 
9 Month Follow-up: Physical and neurological exam, completion of questionnaires, 
assessment of adverse events, LBP concomitant medications and therapies. 
• 
12 Month Follow-up: Physical and neurological exam, completion of questionnaires, 
assessment of adverse events, LBP concomitant medications and therapies. 
• 
24 Month Long-term Surveillance:  To be performed in RF Ablation arm subjects 
only. Physical and neurological exam, completion of questionnaires, and assessment of 
adverse events. 
• 
Crossover:  Intracept procedure will be offered to Control arm subjects following the 
12-month follow-up visit.  The study clock will reset for Control arm subjects who 

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elect crossover; they will undergo a 6-week post-crossover MRI and be followed at 3 
and 6 months post-crossover as described above. 
• 
RF Ablation arm subjects that consent to participate in the five-year sub study will 
have an additional 36, 48, and 60 month follow-up with physical and neurological 
exam and questionnaire collected. 
 
 

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2.0 LIST OF ABBREVIATIONS 
 
510(k) 
Premarket Notification, per FDA 
ADE 
Adverse device effects 
AE 
Adverse events 
ASADE 
Anticipated serious adverse device effect 
BDI 
Beck Depression Inventory 
BMI 
Body mass index 
BVN 
Basivertebral nerve 
BVF 
Basivertebral foramen 
C 
Cervical (vertebral level) 
CFR 
Code of Federal Regulations 
CRA 
Clinical research associate 
CRF 
Case report form 
CT 
Computed tomography 
DDD 
Degenerative disc disease 
eCRF 
Electronic case report form  
EQ-5D-5L 
EuroQOL quality of life instrument 
EU 
European Union 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICH 
International Conference on Harmonisation 
ID 
Identification 
IDET 
Intradiscal electrothermal therapy 
IRB 
Institutional Review Board  
ISO 
International Organization for Standardization 
ITT 
Intent-to-Treat 
L 
Lumbar (vertebral level) 
LBP 
Lower back pain 
MRI 
Magnetic resonance imaging 
NSAID 
Non-steroidal anti-inflammatory drug 
ODI 
Oswestry Disability Index 
PEBAX 
Polyether block amide 
PEEK 
Polyether ether ketone 
PP 
Per Protocol 
QALY 
Quality Adjusted Life Years 
RF 
Radiofrequency 
S 
Sacral (vertebral level) 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SF-36 
Short Form-36 instrument 
SMT 
Spinal manipulative therapy 
TENS 
Transcutaneous electrical nerve stimulation 
USADE 
Unanticipated serious adverse device event 
US 
United States of America 
VAS 
Visual analogue scale 
VB 
Vertebral body 
 
 
 
 
 
 
 
 
 
 

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3.0 BACKGROUND 
3.1 
Causes of Low Back Pain 
The causes of low back pain (LBP) are varied and complex. Traumatic or degenerative conditions 
of the spine are the most common causes of LBP and there are known pathologic changes that 
occur in the intervertebral disc, which lead to the subsequent abnormal loading of the adjacent 
vertebral bodies. In addition, it is known that afferent nerve fibers carry pain signals associated 
with spinal degeneration from the low back to the spinal cord and ultimately to the brain. Tissue 
sources of LBP are generally believed to include the paraspinal musculature, facet joints, and the 
intervertebral disc. Acute muscle strains typically heal within days to weeks with activity 
modifications, analgesics, and rehabilitation. Radiculopathy can include leg pain, numbness, and 
weakness, often due to spinal nerve root compression from either disc herniation or other sources 
of nerve compression. Alternatively, chronic mechanical LBP (back pain localized to the lumbar 
spine exacerbated by loading) typically does not include symptoms of nerve root compression and 
is thought to be caused most frequently by degenerative disc disease (DDD). Approximately 10% 
of acute LBP patients go on to have chronic pain, which is defined as pain lasting longer than 3 
months (Bogduk and McGuirk 2002; Merskey and Bogduk 1994). 
The classical degenerative cascade, as first described by Kirkaldy-Willis, consists of the widely 
accepted pathophysiologic model that describes the degenerative process as it affects the lumbar 
spine and individual motion segments (Kirkaldy et al 1978).  The degenerative process is generally 
believed to occur in 3 phases, dysfunction, instability and restabilization, that comprise a 
continuum, with gradual transitions to each subsequent phase. 
The typical initiating event in the cascade involves the loss of internal disc integrity. 
Circumferential tears or fissures in the outer disc annulus characterize this loss histologically. In 
particular, tears, which may result from repetitive microtrauma, may be accompanied by vertebral 
endplate separation or failure that subsequently interrupts blood supply to the disc and impairs 
nutritional supply and waste removal. Since the outer third of the annulus fibrosis is innervated, 
tears or fissures in this area may be painful. Experimental evidence suggests that most episodes of 
chronic LBP are a consequence of disc injury, rather than musculotendinous or ligamentous strain. 
Magnetic resonance images (MRIs) obtained at this stage may reveal desiccation, disc bulging 
without herniation, or a high-intensity zone in the annulus. Changes associated with facet joints 
during the dysfunctional phase may include synovitis and hypomobility, which implicate the facet 
joint as a possible pain source. 
The next phase of the cascade consists of disc-related changes including multiple annular tears 
(e.g., radial, circumferential), internal disc disruption and resorption, and loss of disc-space height. 
Concurrent changes in the facet joints include cartilage degeneration, capsular laxity, and 
subluxation. The biomechanical result of these alterations may include segmental instability. 
The last phase of the degeneration cascade involves further disc resorption, disc-space narrowing, 
vertebral endplate destruction, disc fibrosis, and osteophyte formation; this phase is generally 
referred to as stabilization. Pain at this phase of joint degeneration may have a higher incidence 
than in phases 1 and 2; however, there can be substantial variation in different motion segments 
for any given individual and in reported pain responses for patients of similar ages. 
While the classical model represents the standard reference for lumbar degeneration, an increasing 
body of evidence suggests the fundamental basis of disc degeneration may be associated with 
structural changes associated with microdamage at the vertebral endplate; it is this damage that 

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may initiate the sequence of events precipitating DDD (Rajasekaran et al 2008).  It should be noted 
that vertebral endplate changes can be identified on an MRI using the classification system 
described by Modic (Modic et al 1988). 
In summary, the degenerative cascade occurs due to the body’s response to repetitive trauma and 
loading through the spinal column. The associated pathologic changes at the motion segment (such 
as loss of disc-space height) can be visualized radiographically and confirmed histologically.  
 
3.2 
Epidemiology of Chronic Low Back Pain 
Low back pain (LBP) is the most expensive, benign condition treated in industrialized countries 
and is the most common cause of activity limitation in individuals younger than 45 years of age 
(Kelsey and White 1980).  LBP is second only to the common cold as a cause of lost productivity; 
it is the fifth most frequent cause for hospitalization and the third most frequent cause for surgery 
(Anderssen and Frymoyer 1997; National Center for Health Statistics, 1978; National Center for 
Health Statistics 1973a; National Center for Health Statistics 1973b).  Although acute LBP has a 
favorable prognosis, chronic low back pain (CLBP) - and its associated disability - have profound 
societal impacts.  Specifically, CLBP is the leading cause of work-related disabilities. In the United 
States, an estimated 149 million work days are lost every year because of low back pain, with total 
costs estimated to be 100 to 200 billion dollars a year (of which two-thirds is due to lost wages and 
lower productivity) (Guo et al 1999; Katz 2006; Rubin 2007).  The lifetime prevalence of non-
specific (common) low back pain is estimated at 60% to 70% in industrialized countries (one-year 
prevalence 15% to 45%, adult incidence 5% per year) (Elders and Burdorf 2004).  For these 
reasons, the availability of cost-effective, safe, and efficacious treatments for acute and CLBP are 
of substantial importance to individual patients, physicians, and the health-care system as a whole. 
 
3.3 
The Differential Diagnosis of Chronic Lower Back Pain 
A definitive and confident identification of the primary source of clinically severe chronic LBP 
remains a challenge to clinicians. As with many spine disorders, the diagnosis of LBP and the 
attribution of its cause generally result from the confluence of clinical and radiographic findings. 
Specifically, the current standard used to diagnosis LBP involves conducting a combined review 
of clinical imaging study results (e.g., MRI and X-ray), patient histories, and physical 
examinations. 
Most episodes of acute LBP resolve spontaneously within 6 weeks of onset. For patients who have 
continued pain and disability beyond this 6-week period, LBP can result in long-term chronic 
disability. The diagnosis of chronic LBP is characterized by patient complaints of tightness or 
stiffness in the low back and paraspinal region; patients generally report worsening pain associated 
with prolonged standing, activity, or upon rising in the morning. The pain may radiate toward the 
buttocks, or to the posterior or anterior thighs. (Note that thigh pain arising from LBP is usually 
distinguished easily from leg pain of neurogenic origin [i.e., sciatica], since neurogenic pain is 
typically described as a burning, shooting, or stabbing pain that travels down the back of the leg 
towards the foot, is usually accompanied by numbness or tingling, and may present with a 
neurologic deficit.) 
In addition to patient complaints, lumbar degeneration is also characterized by pathologic changes 
in the disc and the subsequent abnormal loading of the adjacent vertebral bodies as seen on patient 

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imaging. Specifically, DDD is characterized radiographically by loss of disc-space height, 
osteophyte formation, and endplate sclerosis. Additionally, the alteration in the lumbar motion 
segment can frequently lead to changes in the adjacent vertebral bodies. The identification of these 
changes, known as Modic changes, is possible with MRI (and occasionally plain radiographs). 
In 1988, Modic (Modic et al 1988) described and validated vertebral anomalies that were detected 
by MRI. The anomalies were defined as signal changes in the vertebral bone extending from the 
vertebral endplate and included 3 specific types: 
• Type 1: Changes are characterized by fibrovascular replacement and demonstrate 
decreased signal intensity on T1-weighted MRIs and increased signal intensity on 
T2-weighted MRIs. Histopathology of Type 1 changes demonstrates disruption and 
fissuring of the vertebral endplate and vascularized granulation tissue within the adjacent 
marrow, producing prolongation of T1 and T2 relaxation times. Osteoblasts and osteoclasts 
are present with thickened trabeculae. 
• Type 2: Changes are represented by increased signal intensity on T1-weighted MRIs and 
an iso- or slightly hyper-intense signal on T2-weighted MRIs. Type 2 changes show 
evidence of vertebral endplate disruption with yellow marrow replacement in the adjacent 
vertebral body (VB), resulting in a shorter T1. Vertebral endplate damage appears more 
chronic with reactive trabeculae thickening. Type 1 changes appear to convert to Type 2 
changes over time. 
• Type 3: Changes are represented by decreased signal intensity on both T1- and 
T2-weighted MRIs. These correlate with sclerosis on plain radiographs, which is a 
reflection of dense woven bone within the VB rather than marrow elements. 
Modic changes are uncommon in asymptomatic individuals who do not present with DDD. For 
example, in the series by Toyone et al., (Toyone et al 1994) only 9.6% of patients without DDD 
had Modic changes. In this same series, 73% of patients with Type 1 Modic changes had LBP as 
opposed to 11% of patients with Type 2 Modic changes. Further, in a study of 60 asymptomatic 
volunteers who were 20 to 50 years of age, the prevalence of Modic changes was 3% to 10% 
(Weishaupt et al 1998).  In particular, the radiologist saw Type 1 changes in just 1 of 300 lumbar 
motion segments. 
In a population-based sample of 412 patients who were 40 years of age, Modic changes were 
observed in the lumbar spines of 9.6% of the patients without DDD and 34.1% of the patients with 
DDD (Kjaer et al 2006).  In addition, this study indicated that DDD in the absence of Modic 
changes is a relatively quiet disorder (i.e., generally asymptomatic), whereas DDD in association 
with Modic changes is frequently observed with clinical symptoms. In this same population-based 
sample, three subgroups of patients were described: those with both DDD and Modic changes, 
those with only DDD, and those without DDD or Modic changes. An investigation of the clinical 
patterns across the three subgroups revealed that individuals with both DDD and Modic changes 
have a more pronounced clinical profile of LBP than those with neither finding. Overall, the study 
concluded that Modic changes constitute a crucial element in the evaluation of the degenerative 
process. 
In order to investigate associations between Modic changes and the frequency and intensity of 
LBP and sciatic pain, a cross-sectional study of 228 middle-aged male workers was conducted 
(Kuisma et al 2007).  Sagittal T1- and T2-weighted MRIs from these patients were reviewed and 
both vertebral endplates of 1,140 lumbar bodies were graded for the type and extent of Modic 

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changes. Logistic regression was used to analyze associations of pain variables with Modic 
changes. Overall, 178 Modic changes were recorded in 128 subjects. Of the recorded changes, 
30% were Type I, 66% were Type 2, and 4% were both Type 1 and 2; 80% of the observed changes 
occurred at L4-L5 or L5-S1. Modic changes at L5-S1 showed significant association with pain 
symptoms and increased frequency of LBP. Type 1 Modic changes and extensive Modic changes, 
in particular, were closely associated with pain. 
Other studies reported in the literature have also supported the correlation between Modic changes 
and LBP. For example, one report showed a positive correlation between the evolution of Type 1 
to Type 2 changes and a subsequent improvement in symptoms (Mitra et al 2004).  In a different 
clinical study, 60% of patients with Modic changes had LBP compared to 20% of patients without 
Modic changes. Additionally, in this same study, Type 1 Modic changes were observed to be more 
strongly associated with LBP than Type 2 Modic changes (Albert and Manniche 2007). 
Overall, research published over the last 2 decades, including natural history investigations, 
pathogenesis studies, differential diagnosis of Modic change evaluations, and examinations of 
Modic change-LBP associations, demonstrate that Modic changes constitute dynamic markers of 
normal age-related degeneration affecting the lumbar spine. Additionally, recognizing Modic 
changes is critical to the differential diagnosis of chronic LBP as these changes are strongly 
associated with active lower back symptoms (Rahme and Moussa 2008). 
 
3.4 
Pathophysiology of Vertebrogenic Back Pain 
During spinal compressive loading, the VB is responsible for supporting 80% of the load. If the 
load is applied quickly, the VB may fail before either the disc or the cartilaginous endplates, 
resulting in fracture (White and Panjabi 1990).  If the excessive load is applied slowly or 
repetitively, the principal mode of spinal segment injury is degeneration of the vertebral endplate 
(the vertebra/disc interface), which is suspected as being the most common mechanism for the 
initiation of intervertebral disc degeneration (Adams et al 2000).  In contrast to the intervertebral 
disc, the VB and endplate are highly innervated, and therefore, are important sources of spinal pain 
(van Dieen et al 1993).  The basivertebral nerve (BVN) is an intraosseous nerve (figure 1), which 
has been shown to be a branch of the sinuvertebral nerve (Edgar and Ghadially 1976).  The BVN 
enters the vertebra via the posterior neurovascular foramen and has been observed and 
characterized as a major source of afferent vertebral and endplate innervation (Antonacci et al 
1998).  The density of vertebral endplate innervation is comparable to that of the peripheral 
annulus, suggesting that the endplate is an equally important source of pain; this may have 
traditionally been reported as discogenic in origin (Fagan et al 2003).  Indeed, vertebral endplate 
nerves are prototypical pain fibers that demonstrate nociceptor markers such as the 
neurotransmitter Substance P and high affinity nerve growth factor receptor trk-A (Freemont et al 
2002).  The clinical significance of afferent vertebral innervation via the BVN in patients with 
back pain is reinforced by reports of immediate pain amelioration after BVN disruption during 
vertebroplasty. This immediate relief is far more characteristic of a deafferentation mechanism—
in this case probable serendipitous ablation (by the exothermic reaction) or transection of the 
BVN—as opposed to the more commonly conjectured mechanism of restoration of biomechanical 
stability (Freemont et al 2002).  Pain provocation studies on human subjects also support the 
primacy of the BVN as an afferent pathway for nociception (Niv et al 2003). 
 

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Figure 1:  Illustration of the BVN (red) 
 
 
Further evidence for the clinical importance of vertebral innervation is derived from the association 
between vertebral marrow abnormalities on MRIs and presumed “discogenic” pain. It is known 
that VB endplates deflect in response to the intradiscal pressure produced during provocative 
discography (Kuslich et al 1991).  Vertebral endplates in patients with discogenic pain are 
innervated by nociceptors (versus otherwise normal, non-painful discs) (Heggeness and Doherty 
1993) and can elicit a pain response upon direct mechanical stimulation (Niv et al 2003).  
Consistent with these observations, nerve signaling associated with the innervated vertebral 
endplates appears to play a significant role in concordant pain reported by patients during 
provocative discography at the associated disc level. The BVN, which traverses the VB and 
arborizes to the endplates, is likely a significant conduit for this pain signaling (Brown et al 1997). 
During the degenerative process, damage to the VB and endplate adjacent to the degenerating 
intervertebral discs triggers a fibrovascular repair response. This reparative process is observed as 
Modic changes on MRIs. Further, given that the endplates are richly innervated vertebral regions, 
the established correlation between the degenerative cascade, Modic changes, and chronic LBP, 
and based on both the painful response to vertebral endplate deflection during discography and the 
immediate pain relief noted during ablation from vertebroplasty procedures, the endplates are 
considered to be an important source of mechanical LBP. Consequently, vertebral denervation via 
ablation of the BVN is hypothesized to have significant therapeutic benefit. 
 
3.4.1 Discogenic versus Vertebrogenic Back Pain 
As noted previously, the specific source of LBP is often difficult to determine. Therefore, after 
excluding other sources or causes of pain (e.g., compressed nerve root, compression fracture, facet 
joints, and muscular etiology), the VB and endplates should be considered potential pain 
generators. It is now well established that pressurization of the disc during discography causes 
significant mechanical deflection of the bony vertebral endplate (Braithwaite et al 1998).  
Additionally, as shown in a study of awake patients who underwent lumbar surgery using only 
local anesthesia, direct mechanical stimulation of the vertebral endplate is correlated directly with 
severe pain (Sandhu et al 2000). 

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A clear association has been established between the presence of Modic changes, disabling LBP, 
and positive lumbar discography. Modic changes (in particular, Types 1 and 2) are positively 
associated with pain as defined by concordant pain reported by patients during provocative 
discography. Data from multiple independent studies have suggested that Type 1 or 2 Modic 
vertebral endplate abnormalities are among the most specific of all typical MRI observations in 
the prediction of adjacent concordant discography pain at the associated disc level (Toyone et al 
1994; Kjaer et al 2006; Braithwaite et al 1998; Kjaer et al 2005). Modic changes have been reported 
as having a very high specificity (96.0%-96.8%) and positive predictive value (88.0%-91.3%) for 
pain reproduction during discography in patients with chronic LBP (Kuslich et al 1991).  Further, 
it has been shown that moderate and severe Modic changes (i.e., changes extending up to 25% or 
more of vertebral height) correlate 100% with positive concordant pain at the disc-level associated 
with the culprit vertebral endplate (Weishaupt et al 2001).  Finally, denervation of discs or disc 
excision have shown only modest success, perhaps indicating that a primary component of axial 
LBP is not the disc, but rather vertebral pain (Ohtori et al 2006). 
Overall, the relevant data suggest that damage accumulation in the VB adjacent to degenerating 
intervertebral discs triggers a fibrovascular repair response that underlies Modic changes observed 
on MRIs. These innervated vertebral regions are considered to be an important source of 
mechanical LBP. To date, pain relief following disc denervation and/or disc excision (with 
accompanying fusion) has been poor. Consequently, vertebral denervation via disruption of the 
BVN is a reasonable and potentially viable treatment option for patients with chronic LBP. 
 
3.5 
Treatments for Chronic Lower Back Pain 
The management of chronic LBP often involves numerous specialists and may include the use of 
medications, active exercise programs, alternative medical treatments, and manual, educational, 
and behavioral therapies. More invasive treatments may include injection and surgical therapies. 
Non-surgical, conservative care for LBP varies widely as there are no true standards associated 
with the types and durations of physical therapy, medication usage, or interventional treatments. 
Thus, before recommending surgical intervention for chronic LBP, the current standard of care is 
to recommend a patient-appropriate course of non-surgical treatment. 
Standard practice for the treatment of LBP in the US involves a prescription of rest, medication, 
and physical therapy. Patients who do not respond to this conservative treatment may seek 
alternative approaches, such as chiropractic manipulation, massage, or acupuncture. Interventional 
therapies, including nerve blocks, facet blocks, or epidural steroid injections, are also commonly 
prescribed. In cases that are unresponsive to conservative care, surgery may be recommended (e.g., 
fusion or arthroplasty). It should be noted that the rate of lumbar fusion surgery is increasing in 
the US.  In 1992, the US average rate of lumbar fusion was 0.3 per 1000 Medicare enrollees. The 
rate increased over the following decade, doubling to 0.6 per 1000 enrollees in 1998, and reaching 
1.1 per 1000 in 2003 (Weinstein et al 2006).  From 2000 to 2009, the rate of lumbar fusion for the 
treatment of DDD continued to steadily increase by 2.8-3.0 fold (depending on the type of fusion 
procedure performed) (Yoshihara and Yoneoka 2015).  Overall, motion segment degeneration is 
the primary indication leading to fusion surgery in patients under 60 years of age, while spinal 
stenosis is the primary indication leading to surgery in patients over 60 years of age; for this older 
patient population, fusion surgery is adjunctive to a primary decompressive procedure (Deyo et al 
2005). 
 

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3.6 
Non-surgical Treatments for Lower Back Pain 
Non-surgical treatments for LBP include patient education, the use of analgesics, exercise, 
physical treatments, spinal manipulative therapy (SMT), needle acupuncture, multidisciplinary 
rehabilitation, and injections and nerve treatments. From a joint practice guideline from the 
American College of Physicians and the American Pain Society, a discussion of each of these 
treatments follows (Chou et al 2007). 
 
3.6.1 Education 
The purpose of educating patients about LBP is to provide reassurance regarding the diagnosis, 
information associated with the prognosis, encouragement toward self-care, and advice to remain 
physically active despite discomfort or pain (Brox et al 2008).  Education may include short 
interactions with a health provider, lay group discussions, educational booklets, electronic 
materials, or web-based discussion groups (Airaksinen et al 2006).  
 
3.6.2 Analgesics 
There are numerous types of analgesics available for chronic LBP, including acetaminophen and 
nonsteroidal anti-inflammatory drugs (NSAIDs). Acetaminophen generally is recommended as the 
first-line medication for chronic LBP, with NSAIDs as a second-line medication in cases where 
acetaminophen is ineffective or contraindicated. Should neither class of medication prove 
effective, weak opioid analgesics such as codeine or tramadol may be used on a short-term basis. 
If severe pain persists, stronger opioid analgesics such as morphine, oxycodone, or fentanyl may 
be prescribed, with caution. 
Adjunctive analgesics include tricyclic antidepressants (TCAs), selective serotonin reuptake 
inhibitors, serotonin-norepinephrine reuptake inhibitors, and antiepileptic drugs.  Commonly 
prescribed TCAs include amitriptyline, desipramine, and nortriptyline (Chang et al 2008). 
 
3.6.3 Exercise 
Back strengthening exercises are defined as supervised, dynamic, progressive resistance exercises 
that include isolation of the lumbar extensor muscles (Mayer et al 2008).  Modes of administration 
for this form of exercise include machines, benches, Roman chairs, free weights, floor exercises, 
and stability ball exercises. Trained personnel in rehabilitation clinics or fitness centers typically 
supervise strengthening exercises, which are based on the principles of muscular strength 
development and generally require 1 to 3 training sessions each week (Medicine ACoS 2010).  
Strengthening exercises are performed throughout the full, pain-free range of motion of back 
extension, while exercise load gradually and progressively is increased via weight stacks, metal 
plates, machine angle, or back position. Back strengthening exercises usually are performed at a 
higher intensity than other forms of exercises that have been advocated for chronic LBP.  
 
3.6.4 Physical Treatments 
Interferential current, shortwave diathermy, and therapeutic ultrasound are physical treatments 
generally applied by physiotherapists. Specifically, interferential current involves the application 

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of a medium frequency, alternating current that is modulated to produce low frequencies of up to 
150 Hz (Hurley et al 2001); shortwave diathermy, which is often used to treat soft tissue disorders 
and arthritis, involves the application of shortwave electromagnetic radiation (continuous or 
pulsed) within a frequency range of 10 to 100 MHz (Kitchen and Partridge 1992); and therapeutic 
ultrasound involves the combination of a generator, which produces electromagnetic energy with 
a frequency of 0.5 to 3.5 MHz, and a transducer, which converts the electromagnetic energy to 
mechanical energy with a similar frequency and an intensity of up to 3 W/cm (Van Der Windt et 
al 2002). 
Separate from these methods, application of heat is often used due to its beneficial effects on blood 
circulation and muscle stiffness. Through these effects, it may result in relaxation, pain relief, and 
improvements in functional disability. 
Lumbar traction is another physical treatment that is applied by putting a single harness around 
the lower rib cage and a second harness around the iliac crest; a force, equivalent to at least 25% 
of the patient’s body weight, is then applied to separate both harnesses. The duration and level of 
exerted traction is varied in a continuous or intermittent mode. Different types of traction include 
manual traction (i.e., traction exerted by the therapist, using the patient’s head, arms, or legs), 
motorized traction (i.e., traction exerted by a motorized pulley), suspension (i.e., traction exerted 
by gravitational forces, through the body weight of the patient), and bed-rest traction (i.e., traction 
exerted by a pulley and weights) (van den Hoogen et al 1995). 
Transcutaneous electrical nerve stimulation (TENS) represents a non-invasive therapeutic 
modality for pain relief. This technique consists of electrical stimulation of the peripheral nerves 
via skin surface electrodes. In clinical practice, various types of TENS applications are used, which 
generally differ from one another with regard to intensity and electrical characteristics.  
Finally, massage therapy is defined as soft tissue manipulation using the hands or a mechanical 
device. Different massage techniques are used, such as effleurage, petrissage, friction, kneading, 
or hacking, either in a classical manner or in a manner through which the rules of massage from 
physical medicine are combined with those of acupuncture. In clinical practice, massage is often 
either applied as a sole treatment or is used in combination with other therapies such as exercise. 
 
3.6.5 Spinal Manipulative Therapy 
High-velocity, low-amplitude SMT involves applying a manual thrust to spinal joints slightly 
beyond their passive ranges of motion, whereas mobilization involves application of manual force 
without thrusting (Halderman and Phillips 1991).  SMT can be administered by several groups of 
trained practitioners, including chiropractors, osteopathic physicians, and physical therapists. The 
dose of SMT required for clinical improvement of chronic LBP is unclear, although the United 
Kingdom Clinical Practice Guideline (UKCPG) recommends a maximum of 9 SMT sessions over 
a period of up to 12 weeks (Low back pain 2009).  
 
3.6.6 Needle Acupuncture 
Needle acupuncture involves stimulation of anatomical points by penetrating the skin with solid 
metallic needles that are either manually or electrically stimulated (Ammendolia et al 2008); the 
treatment is administered by licensed acupuncturists and other credentialed providers (e.g., 
traditional Chinese medicine practitioners, physicians, chiropractors, or physiotherapists). In a 

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typical treatment for chronic LBP, approximately 20 to 30 needles are applied to the skin along 
meridians (vital energy pathways in the body) and associated acupuncture points and left in place 
for 20 to 30 minutes. The United Kingdom Clinical Practice Guideline (UKCPG) recommends a 
maximum of 9 acupuncture sessions over a period of up to 12 weeks (Low back pain 2009).  
 
3.6.7 Multidisciplinary Rehabilitation 
Multidisciplinary rehabilitation programs vary widely, but usually consist of 4 components: 
physical; behavioral; vocational; and pharmacologic management. Multidisciplinary rehabilitation 
is usually delivered by at least 3 healthcare providers with different clinical backgrounds, 
combining intensive supervised exercise therapy with behavioral approaches to decrease pain, 
improve function, reduce the impact of psychological co-morbidities, and foster a return to normal 
activities for patients with chronic LBP (Guzman et al 2001).  
 
3.6.8 Injections and Nerve Treatments  
Epidural injections are possible by the caudal, sacral, sacral transforaminal, lumbar midline, 
paralumbar (lateral), and lumbar transforaminal approaches. They are given “blindly” or with 
X-ray guidance (by either fluoroscopy or computed tomography [CT]); various glucocorticoids 
are also used either alone or in combination with a local anesthetic or saline. Spinal nerve root 
blocks are normally carried out under fluoroscopy or CT guidance and are given “periradicularly” 
(i.e., in the vicinity of the nerve root). Corticosteroids that are most often injected include 
methylprednisolone, triamcinolone, and dexamethasone (Mayer et al 2010; Chou et al 2009). 
Facet block injections involve the instillation of local anesthetic and/or corticosteroid into a facet 
joint or around its nerve supply (ramus medialis of the ramus dorsalis). Fluoroscopic monitoring 
is necessary to check the position of the needle. When a joint is anesthetized through its nerve 
supply, typically at least 2 nerves (rami dorsalis) are blocked for each joint. 
Myofascial trigger points are hyperirritable loci within a taut band of skeletal muscle. Trigger 
points are located in the muscle or its associated fascia. They are painful on compression and can 
evoke a reliable, characteristic referred pain, with or without autonomic response. Injection in the 
trigger points results in the selective destruction of mature myocytes by local anesthetic, saline 
infiltration, dry needling, or the “breaking of the reflex mechanism” of the pain. 
 
3.7 
Surgical Treatments for Chronic Lower Back Pain 
Surgical approaches to LBP treatment include intradiscal procedures, fusion surgeries, and total 
disc arthroplasty. Descriptions of these treatments follow. 
 
3.7.1 Intradiscal Procedures 
A variety of intradiscal procedures have been developed because the disc is frequently the 
presumed source of many painful spinal and radicular syndromes. A prospective, randomized, 
double-blind study of intradiscal injections, however, demonstrated that painful discs show no 
statistically significant benefit from intradiscal administration of corticosteroids relative to local 
anesthesia (Simmons et al 1992).  Despite this, other therapies have been evaluated for the 

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treatment of “discogenic” pain and include chymopapain injections to achieve nucleolysis, 
percutaneous manual nucleotomy with various mechanical devices, thermal vaporization using a 
laser, and percutaneous decompression with nucleotomy using ablative technology (nucleoplasty). 
The use of diagnostic discography has been combined with therapeutic percutaneous intradiscal 
procedures in patients who demonstrate a concordant pain response. These include intradiscal 
electrothermal therapy (IDET), percutaneous laser disc decompression, percutaneous 
radiofrequency annular neurolysis, and nucleoplasty (Pinzon 2001).  These procedures are 
postulated to shrink collagen fibers and coagulate neural tissues, thereby alleviating nociception 
produced by the mechanical loading of a painful, degenerated disc. 
As a treatment for chronic LBP due to “discogenic” pain, IDET is performed using radiographic 
placement of a 17-gauge introducer needle through a posterolateral annular wall into the nucleus. 
Symptomatic discs are determined by discography. A navigable catheter with a temperature 
controlled, thermal-resistant coil is passed through the needle so that it curls along the posterior 
inner annulus. Catheter temperatures are slowly raised to 90°C, causing thermocoagulation of 
intradiscal and inner annular collagen, as well as associated nociceptors. Reduction in pain 
symptoms may result from denervation or shrinking and remodeling of the disc structure, or both 
(Pauza et al 2004). 
The outcomes of IDET, however, are generally poor. Specifically, there have been 2 randomized, 
controlled studies designed to evaluate the safety and efficacy of IDET. In the first study, moderate 
pain reduction in an IDET-treated group was observed relative to a sham group (Freedman et al 
2003); it was noted, though, that the data in this study did not exclude placebo effects. In the second 
study, although the IDET procedure was shown to be generally safe, there was no significant 
reduction in pain (i.e., no benefit) observed in patients who received treatment with IDET (Fritzell 
et al 2001). 
 
3.7.2 Fusion Surgery 
Spinal fusion is the most common surgical procedure performed for LBP. Spinal fusion surgery 
attempts to eliminate pain by preventing motion across a painful spinal segment and stabilizing 
the spine. Spinal instrumentation is often used with spinal fusion to improve the fusion rate. 
Lumbar fusion for LBP is controversial due to relatively low efficacy rates, high costs, 
co-morbidities, and the transfer of stress to adjacent spinal segments, which may lead to 
degeneration at adjacent levels. 
The fusion approach may be posterior, anterior, or both. Radiographically, successful fusion is 
usually obtained in 60% to 90% of patients who undergo a posterior fusion procedure. Anterior 
interbody fusions typically have a successful fusion rate above 90%. Unfortunately, clinical 
outcomes following lumbar spinal fusions for LBP are satisfactory in only 40% to 70% of the 
patients and clinical success does not always correlate with the presence or absence of a successful 
fusion (Shealy 1975).  Even with rigid posterior instrumentation, there is still micromotion across 
the disc space, which may account for persistent symptoms in some patients. Residual symptoms 
in other patients may be related to approach related muscle denervation or disruption of the 
adjacent facet joints.  
Circumferential fusions are performed to fuse both the anterior interbody space and posterolateral 
spine. Historically, this was accomplished through both an anterior and posterior procedure. 
Although successful fusion rates are in excess of 95% with this combined approach, most studies 

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still only report clinical success in approximately 70% of the patients. Additionally, the morbidity 
of 2 procedures can lead to prolonged recovery and rehabilitation. 
Posterior lumbar interbody fusion or transforaminal lumbar interbody fusion can allow posterior 
decompression and concurrent anterior column stabilization, while avoiding the morbidity of a 
separate anterior operation. The drawbacks include limitations on the size of the anterior graft or 
implant, nerve root injury, epidural fibrosis and chronic radiculitis, and potential instability from 
resection of the facet joints needed for exposure. 
 
3.7.3 Total Disc Arthroplasty 
Total disc arthroplasty (i.e., artificial disc replacement) is an alternative to spinal fusion surgery 
for patients who have painful lumbar motion segments due to DDD. The artificial disc is designed 
to preserve range of motion, which (theoretically) should diminish the incidence of adjacent level 
degeneration. Unfortunately, the overall efficacy in relieving pain is comparable to that of lumbar 
fusion surgery. This has caused a lack of uniform acceptance of total disc arthroplasty as a common 
treatment for LBP. 
 
 
3.8 
RF Ablation of the BVN for Treatment of Vertebrogenic Back Pain 
The clinical utility of radiofrequency (RF) energy to treat diseases and conditions in general by 
heating and/or destroying tissue has been established over many decades of use in the medical 
profession. RF energy is used to heat tissue for the purposes of remodeling, shaping, or ablating 
(van Dieen et al 1993), for controlled treatment of tumors (Lord et al 1996), and for nerve 
destruction (Dupuy et al 2000). 
In particular, the use of RF ablation for the treatment of nerve pain in other parts of the body has 
been extensively reported in the literature (Lord et al 1996).  In particular, RF ablation of lumbar 
facet joints is commonly performed (van Dieen et al 1993; Shealy 1975).  RF ablation has also 
been utilized in the VB for palliative treatment of pain due to metastatic bone lesions (Mayer et al 
2008).  Finally, RF ablation has been used as a definitive treatment for osteoid osteomas of the 
extremities and spinal column (Lindner et al 2001; Mahnken et al 2006). 
As stated previously, the BVN is an intraosseous nerve within the VB that plays a role in afferent 
pain transmission. Given that RF ablation of nerves has been shown to be safe and to improve pain 
in other settings, RF ablation of the BVN appears to be a reasonable clinical target for the treatment 
of chronic back pain (Lord and Bogduk 2001). 
The Intracept® System is a novel therapy intended to relieve CLBP in the presence of Modic type 
1 or 2 abnormalities by denervating the BVN within the VB. The device is a percutaneous, 
minimally invasive system that ablates nerve tissue via a transpedicular or extrapedicular 
approach. The technique is based on the principle of bipolar tissue ablation using RF energy as a 
heat source. Ablation of the BVN occurs in a controlled manner by limiting the ablation zone to 
approximately 1.0 to 1.2 centimeters in diameter. This percutaneous procedure is intended to 
provide an alternative to patients who have failed conservative therapy and are considering more 
invasive surgical interventions.  To this end, patients eligible for participation in the Intracept 
studies will be selected based on current clinical examinations and previous medical histories that 
are indicative of chronic LBP of vertebrogenic origin. The diagnosis will be further correlated by 

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confirmation of Modic changes.  Finally, extensive exclusion criteria will be applied to ensure that 
patients with confounding conditions or other sources of back pain will not be entered into the 
study. 
 
3.9 
Clinical Experience to Date 
Two prior clinical studies have been performed to evaluate the Intracept System:  A feasibility 
study and a pivotal clinical trial to support 510(k) clearance by the FDA for the specific indication 
of RF ablation of the BVN for the treatment of CLBP.  The design and results of these studies are 
briefly described below. 
3.9.1 Feasibility Study 
Study Design: The feasibility study was a prospective, single arm, international study performed 
to demonstrate preliminary effectiveness and safety of the Intracept System for treatment of 
chronic low back pain of at least 6 months duration that had not responded to at least three months 
of conservative care, and was also accompanied by either Type 1 or Type 2 Modic changes on an 
MRI (Magnetic Resonance Imaging), or positive provocative discography.   
Methods:  17 patients were enrolled, and 16 successfully received treatment with the Intracept 
System.  One patient was not treated due to spinal anatomy that was not amenable to treatment.  
Patients were evaluated at discharge, 6 weeks, 3 months, 6 months and 12 months.  Each visit 
consisted of directed physical and neurological exam, assessment of adverse events and 
medications as well as patient reported outcomes; a visual analog scale (VAS) and ODI.  
Additionally, MRI images were collected at baseline and during each follow up visit for analysis 
by a core lab. 
Results:  The mean reported ODI (disability) and VAS (pain) scores showed significant statistical 
improvement in patient reported pain and low-back-pain-specific disability when compared to 
baseline at all study follow-up time points.  Mean baseline ODI scores decreased from 52 ± 13 at 
baseline to 23 ± 21 at three months follow-up (p < 0.001) and this result was maintained through 
12 months.   VAS scores decreased from 61 ± 22 at baseline to 45 ± 35 at three months follow-up 
(p < 0.05).  The overall patient treatment success using the pre-defined criteria at twelve months 
was 13 out of 16 patients or 81%. There were no device- or procedure-related serious adverse 
events in the study (Becker et al 2016). 
Conclusions:  this feasibility study demonstrated that the Intracept System was effective for 
treatment of chronic low back pain with successful outcomes for all primary and secondary 
efficacy measures.  Further, the required treatment procedure had a high degree of procedural 
success and safety, with no adverse procedure or treatment-related effects as confirmed by 
independent core lab review of post-treatment MRI exams. Investigators and patients reported 
good success and satisfaction with the treatment procedure and results.  Based on the results of 
this study, a pivotal clinical trial was undertaken (the SMART study). 
3.9.2 Pivotal Clinical Trial – the SMART Study 
Study Design: The SMART Study was a randomized, double-blinded, sham-controlled, 
multicenter, international, investigational device exemption (IDE) trial performed too evaluate the 

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safety and efficacy of RF ablation of the BVN, for the relief of chronic axial low back pain in the 
presence of Modic Type 1 and 2 changes. 
Methods: 225 patients were randomized 2:1 into either the investigational group (147 patients) 
receiving BVN ablation via the Intracept® System, or the control group (78 patients), receiving 
the sham procedure by anchoring the introducer within the pedicle.  Patients were evaluated 
preoperatively as well as postoperatively at 2 and 6 weeks and 3, 6, and 12 months.  The primary 
study endpoint was the mean improvement from baseline to 3 months in the ODI, compared 
between the treatment arms.  
Results: Results of the primary end point analysis for the per protocol (PP) population at 3 months 
showed that the ODI improvement observed in the investigational arm (LS Mean = 20.5 points) 
was statistically superior (p=0.019) to the sham arm (LS Mean = 15.2 points).  This result was 
sustained through one year of follow-up. Furthermore, an analysis of ODI responder rates found 
that 75.6% of patients treated with BVN ablation demonstrated a greater than 10-point, clinically 
meaningful improvement in their low back pain and associated disability at 3 months. There were 
no unanticipated adverse device effects.  There were no device related serious adverse events 
(SAE) and only one procedure related SAE. The rates of transpedicular and neurological events 
reported were minimal and comparable between treatment arms. MRI evaluations at the 6-week 
and 6-month follow-up time points found no evidence of any spinal canal abnormalities, vertebral 
body collapse, or accelerated disc degeneration.  
Conclusions: Ablation of the BVN using a bipolar RF System is safe and effective for the treatment 
of CLBP, since the analysis of the primary study end point showed a significantly greater 
improvement in ODI for the investigational arm over the sham arm in the PP population. BVN 
ablation provides a new, minimally invasive, treatment option for a subset of patients with chronic 
low back pain. 
Based on the review of the results of the SMART study, FDA granted 510(k) clearance of the 
Intracept System on July 9, 2016 for RF ablation of the BVN for treatment of CLBP in the presence 
of Modic type 1 and 2 changes. 
 
4.0 DEVICE DESCRIPTION 
4.1 
The Intracept® Intraosseous Nerve Ablation System (Intracept System) 
The Intracept System is comprised of two basic, sterile, single use components:  
• 
The Intracept Access Instruments (Instrument Set) is an instrument kit containing a trocar, 
cannulas and guides that provide access to the intended site of RF ablation.   
• 
The Intracept Flexible Bi-Polar RF Probe (RF Probe) conducts RF energy to the target 
location.  
The Intracept System is shown in Figure 2. 
 

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Figure 2:  The Intracept System   
 
 
 
The Intracept Access Instruments are described briefly in Table 1 and in more detail in the 
Instructions for Use. It should be emphasized that the Instrument Set is designed specifically for 
RF ablation of the BVN in the VB.  However, it shares many design aspects with several systems 
currently on the market for ablation in other parts of the body. 
Table 1:  Brief Description of Intracept System 
Tool 
Purpose 
Introducer 
Assembly 
Create the initial straight channel through soft tissue and bone; delivers 
the subsequent J-Stylet and Curved Cannula.  
Curved Cannula 
Used in conjunction with the J-Stylet to create a curved delivery 
channel in bone 
J-Stylet 
Used in conjunction with the Curved Cannula to create a curved 
delivery channel in bone 
Straight Stylet 
Create a straight channel in bone beyond the end of the Curved 
Cannula 
Flexible Bi-polar 
RF Probe 
RF Probe which can be delivered through a curved channel 
 
Additionally, a commercially available, legally marketed RF Generator provides RF energy to the 
RF Probe. An Interconnect Cable is provided to connect the RF Probe to the RF Generator.  
 
 
RF Probe 
Intracept Access Instruments 

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5.0 STUDY PROTOCOL 
5.1 
Study Objectives 
The objective of this study is to evaluate the procedural success rate, clinical effectiveness, and 
health-economic profile of using the Intracept® Intraosseous Nerve Ablation System in adult 
subjects with chronic low back pain in the post-market setting. 
5.1.1 Primary Objectives 
The primary efficacy endpoint is the mean change from baseline to 3 months post-treatment in the 
Oswestry Disability Index (ODI). The primary endpoint will be evaluated in both the treatment 
and control groups with between-group comparisons used to assess the success of the Intracept 
System in reducing chronic axial low back pain. 
Safety will also be evaluated as determined by the incidence of severe or serious adverse events 
reported either by the subject or observed by the investigator, relating to the procedure, the device, 
or the spine, either perioperatively or during the follow-up period. 
5.1.2 Secondary Objectives 
The secondary objectives of this study will include evaluation of the improvement in LBP 
associated disability and pain; improvement in quality of life measures; assessment of health 
economic measures; and evaluation of targeting success with the Intracept System. 
• 
Changes in ODI compared to baseline at 6, 9 and 12 month timepoints; and the 
percentage of subjects who have ≥ 10-point reduction in ODI from Baseline to 3 months 
post-treatment 
• 
Changes in the Visual Analog Scale (VAS) compared to baseline at all follow-up time 
points; and the percentage of subjects who have ≥ 1.5 cm reduction in VAS from 
Baseline to 3 months post-treatment 
• 
Changes in quality of life measures (SF-36, EQ-5D-5L, patient satisfaction rating) 
• 
Intracept procedure targeting success based on lesion location on MRI. 
• 
Resource utilization, including procedures and medications, and consequent costs for 
RF ablation and Control arms. 
• 
Incremental differences in costs and quality of life measures between baseline and 
follow-up time points for RF ablation and Control arms, and incremental differences 
between the study arms. 
 
5.2 
Study Design 
This is a prospective, randomized multi-center, controlled study with an optional crossover 
component.          
Subjects will be randomized 1:1 RF Ablation arm vs Control arm; this is an open-label trial.  
Subjects in the RF Ablation arm will receive the Intracept System procedure to treat one or all of 
the functional spine units bounded by L3 and L4, L4 and L5, or L5 and S1 as identified by Modic 
type 1 or 2 changes.  Subjects in the Control arm will continue non-surgical management therapies 
to treat their CLBP and will be offered optional crossover at after 12 months of follow-up.   

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5.3 
Number of Sites 
Between 10 and 25 US sites may participate in the study. 
 
5.4 
Number of Subjects  
Up to 150 enrolled (randomized) subjects.  Based on the results of the SMART study, it is 
anticipated that there will be approximately a 75% screen failure rate.  Thus, approximately 600 
subjects will be screened to achieve 150 enrolled and treated subjects. 
An assessment of the overall (ignoring treatment groups) standard deviation will be performed at 
approximately 50% of subjects being randomized to confirm sample size and statistical power. 
 
5.5 
Study Duration 
Subjects in the RF Ablation arm will be followed for 24 Months following treatment.  At the 24-
month visit, RF Ablation subjects will be approached to participate in a sub-study entailing five 
years of follow-up post procedure (additional study visits at 36, 48, and 60 months).  Control arm 
subjects will be offered optional crossover treatment after the 12-month follow-up visit and will 
be followed for 6 months following crossover.   
It is estimated that this study may take up to 2 years to enroll, therefore from first subject consented 
through last subject 12-month visit, this study will take approximately 42 months for completion 
of all 12-month follow-up.  The subjects in the RF Ablation arm will take an additional 6 months 
to complete the 24-month follow-up.  RF Ablation arm subjects that agree to participate in the sub-
study will have an additional 36 months of follow-up.  
 
5.6 
Study Population 
The study will enroll subjects who are candidates for treatment with the Intracept System; that is, 
skeletally mature patients with chronic (≥ 6 months), isolated low back (lumbar) pain, who have 
not responded to at least six months of non-operative management (conservative care). The 
treatment is limited to L3, L4, L5, and/or S1 vertebrae. The disease state must be accompanied 
with Modic type 1 or 2 changes as seen on MRI.  
 
5.7 
Subject Selection Criteria 
The following section outlines the specific inclusion and exclusion criteria.  Each subject must 
meet all of the inclusion criteria and have none of the exclusion criteria to proceed past the Baseline 
Visit. 
5.7.1 Inclusion Criteria 
Subjects must meet all of the following inclusion criteria in order to be considered eligible for 
participation in this trial: 
1) Skeletally mature subjects age 25 – 70 years, inclusive 
2) Chronic lower back pain for at least six (6) months  

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3) Failure to respond to at least six (6) months of non-operative conservative management.   
4) Oswestry Disability Index (ODI) at time of evaluation of at least 30 points 
5) Baseline Visual Analog Scale (VAS) of at least 4 cm a 10 cm scale 
6) Modic changes (Type 1 or 2) in at least one vertebral endplate, at one or more levels from L3 
to S1, per MRI 
7) Fluent in reading, writing, speaking, and understanding the English language, and is willing 
and able to follow the requirements of the protocol, including the post-operative management 
program and follow-up schedule 
8) Understands the informed consent and signs the institutional review board (IRB) approved 
informed consent form 
 
5.7.2 Exclusion Criteria 
Subjects will be excluded from participating in this trial if they meet any of the following exclusion 
criteria: 
1) Radicular pain by history or evidence of pain or neurological deficit within the past one year. 
Radicular pain is defined as nerve pain following a dermatomal distribution and that 
correlates with nerve compression on imaging. Somatic referred pain is allowed. 
2) Previous surgery performed on the lumbar spine  
i. Note: previous lumbar decompression not affecting spinal stability or 
mechanics is allowed (unilateral or bilateral laminotomy or 
laminoforaminotomy) if procedure was more than six-months prior to 
screening date and all radicular pain has resolved 
3) Current or history of symptomatic spinal stenosis 
4) Current or history of osteoporotic or tumor-related vertebral body compression fracture 
5) Current or history of vertebral cancer or spinal metastasis 
6) Current or history of spinal infection  
7) Metabolic bone disease (e.g. osteogenesis imperfecta) 
8) BMI ≥40 (without rounding) unless there is documentation that obesity is not a primary 
contributing factor for the potential subject’s CLBP (i.e. muscularly dense subject with 
vertebrogenic pain). 
9) History of a fragility fracture (fracture following a low energy injury-vertebral compression, 
hip, wrist, pelvis, etc.) or current treatment with prescription medications for osteopenia.  
10) Any radiographic evidence of other important back pathology, such as: 
a. Nerve root compression, neurogenic claudication, or severe effacement of the thecal 
sac that correlates with radicular pain or muscle weakness  
b. Disc extrusion or disc protrusion >5mm  
c. Facet arthrosis or facet effusion at any lumbar level that correlates with clinical 
evidence of facet mediated low back pain 

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d. Spondylolisthesis 2 mm or greater at any level 
e. Spondylolysis at any level 
11) MRI evidence of Modic changes, Type I or Type II at vertebral bodies other than L3 to S1, 
per MRI 
12)  Any back pathology related to trauma, evidence of vertebral compression fracture or other 
spinal pathology that could affect assessment of response to back pain 
13) Subjects who are bed bound 
14) Demonstrates 3 or more Waddell’s signs of Inorganic Behavior 
15) Any evidence of current systemic infection 
16) Uncorrected bleeding diathesis 
17) Any neurologic problem that prevents early mobilization after surgery or interferes with 
assessment of ODI 
18) Contraindication to MRI or subjects who have allergies to the components of the Intracept 
device specifically nitinol, PEEK (Poly Ether Ether Ketone), stainless steel, or PEBAX (Poly 
Ether Block Amide) 
19) Pregnant, lactating or plan to become pregnant in next year 
20) Evidence of mental instability or uncontrolled depression; subjects requiring new or any 
change in anti-depressants or anti-psychotic medications within 3 months; subjects with a 
Beck Depression Score of greater than 24 
21) Compensated injuries or ongoing litigation regarding back pain/injury, or financial or other 
incentive to remain impaired 
22) Any medical condition that impairs follow-up (i.e. fibromyalgia, rheumatoid arthritis, chronic 
regional pain syndrome, reflex sympathetic dystrophy) 
23) Contraindications to the proposed anesthetic protocol. 
24) Evidence of substance abuse; subjects using prescribed extended release narcotics (e.g. 
fentanyl patch, MS contin, oxycontin) within the 3 months prior to screening and who are 
motivated to remain impaired for continued prescribing of extended release narcotics.  
25) Known, at the time of screening and/or randomization, to require additional surgery to the 
lumbar spinal region within six months 
26) History of SI joint fusion within the past two years 
27) Being treated with radiation, chemotherapy, immunosuppression, or chronic steroid therapy 
(prednisone ,or its equivalent, use of up to 5 mg/qd is allowed, as well as inhalation steroids 
for asthma) 
28) Has a life expectancy of less than 2 years 
29) Has active implantable devices, such as cardiac pacemakers, spinal cord stimulators, etc. 
 

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5.8 
Treatment Plan 
5.8.1 Screening 
A patient is considered a study subject and may begin the required screening procedures after 
he/she has signed the informed consent document.  Once a patient has provided informed consent, 
the site will assign unique subject ID numbers.   
Subjects who are evaluated for participation but do NOT meet eligibility criteria will be considered 
screen failures, and the reason(s) for screen failure will be documented.   
 
5.8.2 Enrollment Monitor 
This study will use an Enrollment Monitor to verify subject eligibility to continue to the Baseline 
Visit.  The Enrollment Monitor will be an independent reviewer who is not involved with subject 
treatment nor affiliated with an investigational site.  The Enrollment Monitor must have 
appropriate expertise in radiology, neurology, orthopedic surgery and pain management.  The 
Enrollment Monitor will not be a Sponsor employee, but will be compensated for his or her time. 
Investigators will submit complete information regarding each potential study participant to the 
Enrollment Monitor.  The Enrollment Monitor will review all subject screening information 
collected prior to the Baseline Visit.  To be deemed eligible to proceed to Baseline, the Enrollment 
Monitor must agree with the site investigator that the subject meets all study eligibility criteria up 
to that point.  In cases of disagreement between the Enrollment Monitor and the site investigator, 
a consulting investigator will make the final determination. The purpose of the Enrollment Monitor 
is to ensure that all subjects meet all eligibility criteria prior to proceeding to Baseline.   
5.8.3 Baseline Assessments 
Once the Enrollment Monitor has confirmed subject eligibility to proceed to the Baseline Visit, 
the subject may be scheduled for the Baseline Visit.  This visit should be scheduled in coordination 
with a potential procedure date such that the patient can undergo the Intracept procedure within 
three weeks of the Baseline Visit, should the subject be randomized to the RF Ablation arm.  The 
following Baseline Assessments will be performed in the office:   
• Physical and Neurological examinations (including documentation of baseline symptoms) 
• Oswestry Disability Index (ODI) 
• Visual Analog Scale (VAS) assessment of pain 
• Short Form Health Survey (SF-36) 
• EQ-5D-5L 
• Documentation of current CLBP concomitant medications and therapies 
Following Baseline Assessments, the subject’s continued eligibility must be confirmed prior to 
randomization (e.g: no neurological deficits, ODI remains ≥ 30, and VAS remains ≥ 4).  Once the 
study subject has completed the Baseline Assessments and continued eligibility has been 
confirmed per the inclusion and exclusion criteria, the subject may proceed to randomization 
(enrollment).  

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5.8.4 Randomization 
A subject is considered enrolled in the trial once they have been randomized. Subjects will be 
assigned in a 1:1 fashion to RF ablation using the Intracept System or to non-surgical management 
(NSM).   
Randomization will be stratified by site only and will use randomly chosen blocks.  The purpose 
of blocking the randomization by site is to ensure a good balance of treatment assignment within 
each study site while maintaining the unpredictability of the assignment. Treatment will be 
provided in a single procedure as described below in Section 5.8.6.   
 
5.8.5 Choosing the Target Vertebral Bodies 
A single motion level segment in the lumbar spine involves the structures that allow the motion to 
occur:  two vertebral bodies and the intervening disc. For the purposes of this study, the focus is 
on the motion due to the cushioning and elasticity of the intervertebral disc. Although motion does 
also occur at the facet joint, the predominant load (80%) passes through the anterior column of the 
spine (VB and intervertebral disc). 
The degenerative cascade, which can lead to chronic low back pain, is believed to be due to 
pathologic changes in the disc and the subsequent abnormal loading of the adjacent vertebral 
bodies. Alteration in the motion segment can frequently lead to changes in the adjacent vertebral 
bodies. Identification of the changes, known as Modic changes is possible on MRI studies. 
Although these Modic changes are frequently seen on both sides of the disc (L4-5 changes would 
be seen in the inferior portion of L4 VB and the superior portion of the L5 VB), they are 
occasionally seen in only one VB.  As noted in Section 3.4, vertebrae are also a likely source of 
pain provoked by discography.  Evidence suggests VB endplates deflect in response to disc 
pressure produced during provocative discography and may be a source of pain. 
The Intracept System therapy is based on the hypothesis that ablation of the BVN in one or more 
VBs may prevent the transmission of pain centrally, thus resulting in an immediate and sustained 
reduction in back pain.  This nerve is thought to be a common pathway for pain transmission from 
spinal pathology; the data from the SMART trial indicate that this hypothesis is clinically 
supported.  
The BVN transmits pain signals from the nociceptors on the endplates caudal and cephalad to a 
given disc. For this reason, even if Modic changes are only observed in one bounding vertebral 
body, both that body and the other vertebral body bounding the affected disc level are treated. In 
this manner, single level DDD necessitates treatment of two adjacent vertebrae, and two level 
DDD requires treatment of three adjacent vertebrae.  
 
5.8.6 Procedure for RF Ablation of the BVN using the Intracept System 
The Intracept procedure can be performed under general anesthesia or a moderate conscious 
sedation protocol per the operator’s preference.  The Intracept study procedure involves a two-step 
process. First, the Intracept Access Instruments are used via a minimally invasive, transpedicular 
or extrapedicular approach to create a channel to the terminus of the basivertebral foramen. 
Fluoroscopic or CT imaging must be utilized frequently throughout the procedure to ensure proper 
entry and placement of the devices. A small incision is made in the skin.  The Introducer Assembly 

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is inserted through the incision and docked at the entry point of the VB pedicle.  Using standard 
techniques, the cancellous bone of the VB is cannulated via the pedicle. Specific procedure 
instructions, including targeting the basivertebral foramen are provided in the Intracept 
Intraosseous Nerve Ablation System Instructions for Use (IFU) document. 
Once VB access is gained, an RF Probe is inserted through the cannula into the central part of the 
target vertebral body and positioned at the terminus of the basivertebral foramen (see Figure 3).   
 
Figure 3: VB access and Positioning at the Basivertebral Foramen 
 
The Introducer Cannula is shown engaging with the VB through an incision (right side of image) and with the 
RF probe deployed at the BVN target (left side of image). 
 
 
Controlled RF energy is delivered at 85°C for 15 minutes to destroy the basivertebral nerve.  The 
pre-specified RF ablation parameters are shown in (Table 2).  Once ablation is complete, the RF 
Probe and Access Instruments are removed and the skin incision repaired. 
 
Table 2:  RF Ablation Parameters. 
Target Temperature 
85oC 
Treatment Time 
900 seconds, 15 minutes 
Temperature Ramp Rate 
1oC/second 
Impedance Limit Set to 
Off 

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5.8.6.1 IMPORTANT NOTES 
1) Due to the nature of this Clinical Protocol, it is not possible to “retreat” a motion segment 
once ablation energy has been delivered to the vertebral body due to a failure to complete the 
ablation procedure.   Re-treatment post RF ablation would interfere with the planned statistical 
analyses as such, no repeat RF ablation is permitted.  In the situation that there is an inability 
to access the BVN target (i.e. hardened bone or inadequate anesthesia); a re-treatment may be 
performed and the subject will be included in the statistical analyses as no RF ablation therapy 
was delivered in the first attempt.   
2)  
3) Setting and verification of the treatment parameters are a critical safety step.  Only the 
treatment parameters defined in Table 2 above are allowed. Under no circumstances should 
treatment parameters be altered, nor should additional or longer thermal treatments be 
provided.   
5.9 
Schedule of Assessments 
In the RF Ablation arm, follow-up visits will occur at 3, 6, 9 and 12 months post-treatment.  An 
additional long-term surveillance follow-up visit will also be performed in the RF Ablation arm 
subjects only at 24 months. RF Ablation arm subjects will be approached at their 24-month visit 
for participation in a sub-study entailing a five-year follow-up post procedure (additional follow-
up visits at 36, 48, and 60 months).    
The Control arm subjects will be followed at 3, 6, 9 and 12 months following the Baseline visit.  
After completion of the 12-month visit, the Control arm subjects will be given the option to 
crossover to receive the Intracept treatment.  Subjects who receive the crossover procedure will 
have their study clock reset, and will have additional post-treatment follow-up visits at 3 and 6 
months.  Subjects from the Control arm who elect not to crossover will cease participation in the 
study following the 12-month visit. The study coordinator will schedule these visits and be 
responsible for making sure that CRFs are complete.   
At each visit, the subject will be interviewed and examined by the investigator.  The investigator 
will assess medical history, perform a physical and neurological examination and the subject will 
complete the patient assessment questionnaires.  The subject will complete the ODI and VAS 
assessments at all visits, as well as the SF-36 and EQ-5D-5L and patient satisfaction 
questionnaires.  Assessments of additional LBP-related therapies, interventions, or medications 
will be documented as well as any procedure, device or spine related adverse events. The data will 
be entered by the site into the relevant CRFs.   
In addition, at 6 weeks following the procedure, subjects in the RF ablation arm, as well as 
crossover subjects, will have an MRI of the spine with sequences described in Section 6.4.  These 
are research-oriented MRIs and will not be interpreted clinically by site radiologists.  The study 
coordinator will submit the MRI in anonymous DICOM format to the study Sponsor as directed.   
A brief summary of the study schedule of assessments is as follows: 
• Screening Visit (may be completed over more than one study visit):  Written informed 
consent.  Collection of demographic information.  Pregnancy test, if indicated. Completion 
of BDI questionnaire.  Review of medical history.  Physical and neurological examination.  
MR imaging.  A standing lateral x-ray may be requested, but is not required.  Review of 

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densitometry if available.  Review of inclusion/exclusion criteria.  Completion of 
questionnaires (ODI, VAS). LBP concomitant medications and therapies 
• Baseline Visit:  Physical and neurological examination. Pregnancy test, if indicated. 
Completion of all questionnaires (ODI, VAS, SF-36, EQ-5D-5L). LBP concomitant 
medications and therapies. 
• Randomization to either Treatment with Intracept System or assignment to Control arm 
will be performed at the baseline visit. 
• Procedure Visit for treatment with Intracept System. 
• 6 Weeks Post-Treatment:  MR imaging (in subjects treated with RF Ablation) 
• 3 Month Follow-up: Physical and neurological exam, completion of all questionnaires, 
assessment of adverse events, LBP concomitant medications and therapies. 
• 6 Month Follow-up: Physical and neurological exam, completion of all questionnaires, 
assessment of adverse events, LBP concomitant medications and therapies. 
• 9 Month Follow-up: Physical and neurological exam, completion of all questionnaires, 
assessment of adverse events, LBP concomitant medications and therapies. 
• 12 Month Follow-up: Physical and neurological exam, completion of all questionnaires, 
assessment of adverse events, LBP concomitant medications and therapies. 
• 24 Month Long-term Surveillance:  To be performed in RF Ablation arm subjects only. 
Physical and neurological exam, completion of all questionnaires, and assessment of 
adverse events. 
• Crossover:  Intracept procedure will be offered to Control arm subjects following the 12-
month follow-up visit.  The study clock will reset for Control arm subjects who elect 
crossover; they will undergo a 6-week post-crossover MRI and be followed at 3 and 6 
months post-crossover as described above. 
• RF Ablation arm subjects that consent to participate in the five-year sub study will have an 
additional 36, 48, and 60 month follow-up with physical and neurological exam and 
questionnaire collected. 
 
A schematic of the study follow-up schedule for both treatment arms in the Main Study is provided 
in Figure 4.  The full schedule of assessments is shown in Appendix 2.  Most assessments in this 
study are routine for back pain studies.  Characteristics of individual assessments are described in 
Section 6.0. 

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Figure 4:  Main Study Schematic 
 
 
 
 

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5.10 
Crossover 
This trial has a crossover component.  At 12 months after the Baseline visit, subjects in the Control 
arm may elect to crossover to receive the Intracept treatment.  The subject may cross over only 
after the 12-month visit is complete.  Control subjects may cross for any reason and must be 
allowed to cross unless the investigator believes the Intracept procedure is medically 
contraindicated, or the subject would no longer benefit from the Intracept treatment.  A subject 
who crosses over must decide whether they are going to proceed with the Intracept procedure and 
schedule the procedure within 30 days of the 12-month visit.   
Site personnel must not, in any way, influence the subject’s decision as to whether to crossover. 
When a subject crosses over, the study visit clock is reset.  Therefore, a crossed subject who is 
treated with the Intracept System will have a 6 week MRI performed, and will have second 3 and 
6 month visits.   
 
5.11 
Study Exit 
Subjects in the RF Ablation arm who are followed to the 24-month visit are considered to have 
completed the main study.  Crossover subjects will be considered to have completed the study after 
the 6-month post-Intracept procedure visit. Subjects in the Control arm who do not crossover will 
be considered to have completed the study after the 12-month visit. The Investigator or designee 
will complete a study exit form.  RF Ablation subjects that consent to participate in the sub-study, 
will be exited from the study at the completion of the sub-study. 
 
5.12 
Study Withdrawal/Termination  
A subject may withdraw from the study at any time if he/she no longer wishes to participate.  If 
subjects elect to withdraw from the study post-randomization, the study coordinator should inquire 
if the subject is withdrawing due to treatment failure (i.e. lack of improvement in low back pain) 
or for other reasons, and document the reason accordingly on the study completion CRF. 
Importantly, any subject who undergoes a non-study-related invasive surgical therapy for back 
pain at any level during follow-up (e.g. lumbar spine fusion) will be considered a treatment failure 
(if in the RF ablation arm), or ineligible for a study RF ablation treatment (if in the Control arm), 
and the subject must be withdrawn from the study. 
If a subject does not respond to at least 3 documented contact attempts and/or misses scheduled 
appointments such that the follow-up visit does not occur, the visit will be documented as a 
“missed visit”.  Subjects who miss a follow-up visit should still be contacted again for their next 
scheduled follow-up visit.  It is important that continued attempts be made to re-establish contact 
at subsequent follow-up visits. A subject should not be deemed lost to follow up and withdrawn 
from the study until the site has documented efforts at achieving subject contact.   
If a subject withdraws from the study or is terminated from the study, the reason must be carefully 
documented on the study completion CRF.  The investigator and study coordinator should 
carefully screen subjects for their ability and desire to participate in the study.  Continued 
participation should be encouraged at every study visit and using telephone calls as necessary.  
Sites should carefully maintain current subject contact information. 

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6.0 STUDY ASSESSMENTS AND OUTCOME MEASURES 
The clinical condition of each subject will be evaluated using an assessment of a combination of 
the following parameters: 
6.1 
Medical History  
The investigator will verify the health of the subject based on medical history, including 
surgeries/medical procedures, significant illnesses, and neurological and/or psychiatric conditions.  
Specific attention will be given to: 
• Waddell’s signs of non-organic behavior; 
• Back and leg pain assessment; 
• Previous back or neck surgery; 
• Previous spinal neurological procedures;  
• Back pathology, including VB compression fracture, spinal stenosis or compression of the 
thecal sac, spondylolisthesis, spondylolysis, disc extrusion or protrusion, nerve root 
compression, facet joint degeneration, trauma, and/or spinal cancer, infection, or disease. 
The investigator will also assess the likelihood of osteoporosis and review densitometry findings, 
if available.  
 
6.2 
Laboratory Tests 
A urine test for pregnancy (female subjects of childbearing potential only) will be performed in-
office at the Screening and Baseline Visits. Women of childbearing potential are defined as any 
female who has experienced menarche and who is NOT permanently sterile or postmenopausal. 
Postmenopausal is defined as 12 consecutive months with no menses without an alternative 
medical cause. 
 
6.3 
Beck Depression Inventory (BDI-II) 
The BDI is a psychometric test of the severity of depression.  It consists of 21 questions, each 
scored from 0-3.  Higher scores indicate worse depression.  It is composed of items relating to 
symptoms of depression such as hopelessness and irritability, cognitions such as guilt or feelings 
of being punished as well as physical symptoms such as fatigue, weight loss and lack of interest 
in sex.  This questionnaire has been used to assess depression in patients with chronic pain.   Total 
scores range from 0-63, within the following categories:  0-13:  minimal; 14-19: mild; 20-28: 
moderate; 29-63: severe depression (Beck et al 1988).  The BDI is used at the Screening Visit as 
a screening tool for depression; potential participants with BDI scores greater than 24 will not be 
enrolled in the study. Participating study sites must have a plan in place in the event of positive 
results of suicidality based on the T score if it is greater than 24, or if the answer to question #9 in 
the Beck Depression Index is “yes.” 
 

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6.4 
Imaging 
During the screening process, MR images of the lumbar spine will be evaluated to confirm 
eligibility. A standing lateral x-ray may also be evaluated to confirm eligibility. The standing 
lateral x-ray should be within 6 months and the MRI within 3 months of the screening date.  If 
available images are beyond those timeframes, they may be requested to be repeated and evaluated 
as part of the screening. 
If the MRI is within the time window, but the study does not clearly show the basivertebral 
foramen at the target level(s) or provide all of the sequences as listed below, a repeat MRI 
may be required for determining the ablation target using the instructions provided as follows: 
It is preferred that all MR studies performed for this clinical trial should be performed with MR 
equipment that has at least a 1.5 Tesla magnet and submitted in DICOM format.  The following 
imaging sequences are required: 
MR Imaging Sequences: 
1. Sequence 1:  Scout images using department/machine protocol 
2. Sequence 2:  Sagittal T1-weighted images, 3 mm slice thickness with 1mm gap. Matrix 
256 x 256 or greater.  Cover full lateral dimensions of vertebral body. TR/TE, NEX, 
bandwidth per institution standard 
3. Sequence 3:  Sagittal T2-weighted images, 3 mm slice thickness with 1mm gap. Matrix 
256 x 256 or greater.  Cover full lateral dimensions of vertebral body. TR/TE, NEX, 
bandwidth per institution standard 
4. Sequence 4:  Sagittal STIR images, 3 mm slice thickness with 1mm gap. Matrix 256 x 256 
or greater.  Cover full lateral dimensions of vertebral body. TR/TI/TE, NEX, bandwidth 
per institution standard 
5. Sequence 5:  Axial T1 from superior L3 endplate to L4-5 disc, 3/1mm, contiguous stack, 
angle to upper L4 endplate Matrix 256 x 192 or greater. TR/TE, NEX, bandwidth per 
institution standard 
6. Sequence 6:  Axial T1 from superior L4 endplate through S1-2 junction, 3/1mm, 
contiguous stack, angle to upper S1 endplate Matrix 256 x 192 or greater. TR/TE, NEX, 
bandwidth per institution standard 
7. Sequence 7:  Axial T2 from superior L3 endplate to L4-5 disc, 3/1mm, contiguous stack, 
angle to upper L4 endplate Matrix 256 x 192 or greater. TR/TE, NEX, bandwidth per 
institution standard 
8. Sequence 8:  Axial T2 from superior L4 endplate through S1-2 junction, 3/1mm, 
contiguous stack angle, to upper S1 endplate Matrix 256 x 192 or greater. TR/TE, NEX, 
bandwidth per institution standard 
Modic changes (Type 1 and/or 2) must be present for study eligibility, and will facilitate 
identification of the target vertebrae for treatment.   
For assessment after treatment, the MR imaging must be performed with the same equipment that 
was utilized for the screening MRI and the study must consist of all sequences as listed above.  
Follow-up MR images of the lumbar spine will be scheduled to be taken at 6 weeks following the 
Intracept procedure and will be evaluated for targeting success by an independent radiologist (see 
Section 9.5.6 Targeting Success for imaging review protocol). 
 

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6.5 
Neurologic and Physical (Orthopedic) Exam 
A detailed and focused neurologic and orthopedic examination will be performed at Screening 
and all follow-up time points during the study.  The examinations will focus on lumbosacral 
spine and nerve root function as well as pain presentation, function and range of motion.  
Investigators will complete a uniform neurologic examination case report form (CRF) at 
screening, and report any subsequent neurological deviations from baseline at each follow-up 
time point.   
 
6.6 
Oswestry Disability Index (ODI) 
The ODI is a 10-item measure of back-pain related disability.  It assesses the impact of back pain 
on activities of daily living and participation.  It is scored on a scale of 0 (no disability) to 100 
(complete disability), with categories of 0-20 (minimal disability), 21-40 (moderate disability), 41-
60 (severe disability), 61-80 (crippling back pain), and 81-100 (bed-bound or exaggerating).  
Several validity studies have been done to determine the minimally clinically important difference, 
which is considered to be approximately 10 points (Fairbank and Pynsent 2000; Copay et al 2008). 
 
6.7 
Visual Analogue Scale (VAS) 
A visual analog scale (VAS) is a commonly used technique to assess subjective, patient-oriented 
outcomes.  The VAS is a 10-cm scale marked at its ends “0 (no pain)” and “10 (worst imaginable 
pain)”.  Respondents will indicate the point on the scale that corresponds to their perceived pain 
intensity of their low back pain.  The distance between the 0 cm origin and the respondent’s mark 
is measured as the pain rating.  Subjects will be specifically instructed to report their average 
low back pain for the last seven days.  Studies have shown that a minimally clinically important 
difference in VAS is considered to be approximately 1.5cm (Ostelo et al 2008). 
 
6.8 
Short Form-36 Instrument (SF-36) 
The SF-36 was developed by the Rand Corporation as part of the Medical Outcomes Study.  It 
consists of 36 scaled questions across the categories of vitality, physical functioning, bodily pain, 
general health perceptions, physical role functioning, emotional role functioning, social role 
functioning, and mental health.  Total scores range from 0-100, where lower scores indicate more 
disability.  It can be used as an indicator of health-related quality of life and also for health 
economics (Ware and Sherbourne 1992; McHorney et al 1993). Specifically, a subset of the SF-
36, the SF-6D, provides a means for using the SF-36 in economic evaluation by estimating a 
preference-based single index measure for health from these data using general population values. 
The SF-6D allows the analyst to obtain QALYs from the SF-36 for use in cost utility analysis. 
 
6.9 
EuroQOL Quality of Life Instrument (EQ-5D-5L) 
The EQ-5D-5L measures health status.  It consists of five multiple-choice items and a VAS scale 
of health (worst vs. best).  EQ-5D-5L responses can be converted to a single index value ranging 
from 0.0 – 1.0, where higher scores indicate better health.  The EQ-5D-5L has been translated to 
over 50 languages, and country-, region-, and condition-specific population norms have been 

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published.  EQ-5D-5L scores are typically presented as a health-related quality of life measure 
and can be applied to cost-utility analyses (Copay et al 2008; Ostelo et al 2008; Ware and 
Sherbourne 1992).   
 
6.10 
Patient Satisfaction 
Satisfaction will be assessed with a short, non-validated questionnaire employing rating-scale 
questions about satisfaction with treatment, willingness to repeat the treatment for the same 
outcome, and willingness to recommend the treatment to a loved one with the same condition.  
Only subjects in the RF Ablation arm and Crossover subjects will be asked to complete this 
questionnaire at the post-treatment follow-up time points. 
 
6.11 
Concomitant Back Pain Medications 
Current and historical concomitant medications for treatment of LBP will be documented at the 
time of screening and will be monitored throughout the study.  Failure to respond to at least six (6) 
months of non-operative conservative management is required for a subject to be eligible for 
participation. The look-back period for concomitant medications may be 6 months or up to many 
years. Documentation of at least six (6) months of non-operative conservative management in the 
designated CRFs is required. 
The name, dosage, and frequency of all medications used for treating back pain since the last study 
visit will be captured. The average daily dosage for each back pain medication will be record for 
the  two weeks (14 days) prior to the visit or for the two-weeks prior to discontinued use of the 
medication.   
 
6.12 
Concomitant Therapy 
Current and historical concomitant therapy for treatment of LBP will be documented at the time 
of screening and will be monitored throughout the study.  Failure to respond to at least six (6) 
months of non-operative conservative management is required for a subject to be eligible for 
participation. The look-back period for therapies, surgeries, and procedures may be 6 months or 
up to many years. Documentation of at least six (6) months of non-operative conservative 
management in the designated CRFs is required. 
All low back pain therapies or interventions will be documented on a designated CRF (i.e., physical 
therapy, acupuncture, chiropractic care, epidural steroids, etc.). 
 
6.13 
Adverse Events 
An AE is defined as any untoward medical occurrence in a subject. Only such events that are 
procedure, device, neurological, or spine-related will be documented for this study.  The 
investigator will make an assessment of procedure or device relatedness of adverse events. All 
reported adverse events will be adjudicated by a third-party Clinical Event Committee (CEC) for 
a final determination of procedure or device relatedness.  

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AEs related to the use of an investigational medical device are considered Adverse Device Effects 
(ADEs). This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device. This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device.  
AEs will be assessed continuously in the study and the types of events noted above will be reported 
as they occur using a specific CRF.  . All reported adverse events will be reviewed by the CEC.  
A summary of AE types, which are further explained in this section, are presented in Table 3:  
 
Table 3:  Categories of AEs 
AEs 
Non-device Related 
Device- or Procedure-Related 
Non-serious 
Adverse Event (AE)a 
Adverse Device Effect (ADE) 
Serious 
Serious Adverse 
Event (SAE)b 
Serious Adverse Device Effect (SADE) 
Anticipated 
Unanticipated 
Anticipated Serious 
Adverse Device Effect 
(ASADE) 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
a Includes all categories. 
b Includes all categories that are serious. 
A preexisting condition is one that was present at the start of the study. A preexisting condition 
will only be recorded as an AE if the frequency, intensity, or the character of the condition 
worsened during the study period. Note: a planned procedure or hospitalization for a preexisting 
condition, without serious deterioration in health, will not be considered an AE.   
An increase in LBP will be reported as a new AE if one of the following criteria is met: 
• 
10 point increase in ODI over baseline (if a subject has not reported this degree of 
functional impact from LBP previously). 
• 
2 point increase in VAS over baseline (if a subject has not reported this degree of pain that 
is similar in location, severity, or nature previously). 
• 
Increase in narcotic medication or a new prescription for narcotic medication that is outside 
of standing post-operative orders or is used beyond the post-operative healing period of 7 
days. 
• 
Invasive medical intervention for treatment of new or exacerbated LBP (i.e., epidural 
injection) 
Note that an abnormal radiographic finding without symptoms does not constitute an AE.  
Examples of events to be reported as being procedure, device, neurological, or spine-related are as 
follows: 
Procedure-Related AE 
An adverse event that is deemed a proximate procedure related adverse event is defined as an event 
that is related to the treatment procedure, but not specifically related to the Intracept device.  
Examples of these types of events include: anesthesia related complications, fluid overload, 

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retroperitoneal hemorrhage due to failed transpedicular cannulization, wound infection or 
transpedicular cannulization that leads to motor deficit, etc. 
Device-Related AEs  
An adverse event that is deemed a proximate device related event or Intracept therapy related event 
may be defined as follows: 
• 
Breakage of the device or any of the components that lead to an adverse or serious 
adverse event 
• 
Over or under heating during the RF ablation that leads to an adverse or serious adverse 
event 
• 
Infection as a result of compromised sterility of the device prior to use (resulting from 
a manufacturing failure) 
• 
Allergic reaction to the device components 
• 
Operative, peri-operative, or post-operative pain associated with or resulting from the 
procedure (including new sensation of pain or increase in original pain) 
• 
Thermal injury to neural, disc or paraspinal tissues (not due to overheating during RF 
ablation) 
• 
Injury to anatomical structures adjacent to the target treatment location  
• 
Vertebral body fracture (with no other traumatic cause) within 6 months of the Intracept 
procedure 
• 
Permanent nerve damage resulting in loss of function or paralysis 
• 
Any new motor deficit, dermatomal sensory loss or radiculopathy with no compression 
seen on MRI, at the nerve root corresponding to the treated level within 6 weeks of the 
treatment procedure 
• 
Herniation/Protrusion at treated level with MRI evidence of thermal zone 
encroachment into the disc space and/or evidence biomechanic instability secondary to 
the RF lesion.  In addition, the neurologic compression is worsened, compared to the 
pre-procedure MRI. 
• 
Foraminal stenosis at treated level with MRI evidence of thermal zone encroachment 
into the disc space and/or evidence biomechanic instability secondary to the RF lesion.  
In addition, the neurologic compression is worsened, compared to the pre-procedure 
MRI 
Neurological AEs  
A neurological examination will be performed at screening, baseline, and at each follow-up visit.  
A neurological deficit will be recorded as an AE when there is a decrease in motor strength of 1 
grade (or more) in a muscle group or 1 grade (or more) dermatomal sensory loss from baseline.  
All reports of significant neurological deficit; defined as a grade 2 or greater motor or dermatomal 
sensory deficit will be reviewed by the CEC. The final determination of procedure- or device-
related, and permanent or transient, neurological deficit will be adjudicated by the CEC.  
Spine-Related AEs  

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A conservative approach was taken when considering events that could potentially be considered 
as related to the spine, and thus, the following categories are examples of events that should be 
reported as potentially being “spine-related”:  aching in limb, arthropathy, back muscle spasms, 
back strain, buttock pain,  compression fracture, leg cramps, leg pain, low back pain, lower 
extremities weakness, lumbar intervertebral discitis, lumbar disc herniation, lumbar radiculopathy, 
lumbar spondylosis, lumbar strain, lumbar vertebral fracture, motor dysfunction, muscle spasm, 
neck pain, nerve root injury, numbness in leg, pain in hip, pain of lower extremities, paraesthesia, 
sacroiliac pain, sciatica, sensory deficit, spondylolysis, tightness of back muscles, and upper back 
pain.  The final determination of spine-related will be adjudicated by the CEC.  
 
Event Severity 
Adverse events will also be rated by severity as mild, moderate, or severe as defined in Table 4. 
The investigator at each study site is responsible for rating the severity of each adverse event. All 
adverse events will be adjudicated for severity by the CEC. 
 
Table 4: Severity of Adverse Events 
Severity of Adverse Event 
Definition 
Mild 
The subject has awareness of signs or symptoms, but they 
are easily tolerated and are of minor irritant type causing 
little to no loss of time from normal activities. Symptoms 
do not require therapy beyond simple interventions and do 
not require a medical evaluation; signs and symptoms are 
transient and improve with simple therapeutic measures, if 
used. 
Moderate 
Events introduce a low level of inconvenience or concern 
to the subject and interfere with daily activities, but are 
usually improved by simple therapeutic measures or 
medication; moderate experiences may cause some 
interference with functioning. 
Severe 
Events cause marked interruption to the subject’s normal 
daily activities. Subject requires therapeutic measures 
(including medication, hospitalization, or prolongation of 
hospitalization, or other treatments). 
Serious Adverse Event (SAE) 
An SAE is defined per ISO 14155 as any event that: 
• Leads to death. 
• Leads to serious deterioration in the health of a subject that 
o Results in a life-threatening illness or injury, 
o Results in a permanent impairment of a body structure or a body function, 
o Requires in-patient hospitalization or prolongation of existing hospitalization, 

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o Results in medical or surgical intervention to prevent permanent impairment to a 
body structure or a body function. 
• Leads to fetal distress, fetal death, or a congenital abnormality or birth defect. 
Note: Severity is not synonymous with Seriousness. A severe rash is not likely to be an SAE.  
However, mild chest pain may result in hospitalization and is therefore an SAE. 
Procedure, device or spine-related SAEs are to be reported to the study Sponsor immediately upon 
occurrence (within 24 hours of discovery).  The investigator will report SAEs to the local IRB as 
required by local policies. 
Serious Adverse Events, Significant Neurological Events, and/or other important clinically 
significant adverse events, including those that are proximate events related to the device or 
procedure, will be recorded on the CRF and reviewed by the Clinical Event Committee. The final 
determination of procedure- or device-related, and permanent or transient neurological deficit, will 
be adjudicated by the Clinical Event Committee.  
 
Unanticipated and Anticipated Serious Adverse Device Effect 
An unanticipated and serious adverse device effect (USADE) is defined as an event that meets the 
definition of an SAE, is definitely or probably device or procedure-related, and was not identified 
in nature, severity or degree of incidence in the study protocol or IFU. USADEs are to be reported 
to the study Sponsor immediately upon occurrence (within 24 hours of discovery). The Sponsor 
will be responsible for evaluating the occurrence of any USADE as it relates to study continuation 
consistent with the appropriate regulations and reporting requirements.  
Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, 
severity or outcome has been identified in the protocol or IFU. ASADEs are to be reported to the 
study Sponsor immediately upon occurrence (within 24 hours of discovery).  The Sponsor will be 
responsible for evaluating the occurrence of any ASADE as it relates to study continuation 
consistent with the appropriate regulations and reporting requirements.  
 
7.0 
ASSESSMENT OF EFFICACY 
7.1 
Primary Efficacy Endpoint 
The primary efficacy variable is the Oswestry Disability Index (ODI) and the primary efficacy 
endpoint is the mean change from baseline to 3 months post-treatment in the ODI. The primary 
efficacy endpoint will be evaluated in both the treatment and control groups with between-group 
comparisons used to assess the success of the Intracept System in reducing chronic axial low back 
pain. 
 
7.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
• ODI 

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o The mean change in disability from Baseline to 6, 9 and 12 months as measured by 
the ODI. 
o The percentage of subjects who have ≥ 10-point reduction in ODI from Baseline to 
3 months post-treatment 
• Visual Analog Scale (VAS) 
o The mean change in pain from Baseline to 3, 6, 9 and 12 months as measured by 
VAS 
o The percentage of subjects who have ≥ 1.5 cm reduction in VAS from Baseline to 
3 months post-treatment 
• The mean change in SF-36 Physical Component Summary (PCS) and Mental Component 
Summary (MCS) scores from Baseline to 3, 6, 9 and 12 months. 
• The mean change in quality of life from Baseline to 3, 6, 9 and 12 months as measured by 
the EQ-5D-5L index. 
• Mean satisfaction ratings at 3, 6, 9 and 12 months post-treatment in the RF Ablation arm, 
as measured on satisfaction rating scales. 
• The percentage of subjects who have radiographic evidence of targeting success based on 
lesion location on MRI. 
 
7.3 
Long-term Surveillance Endpoints 
Subjects in the RF Ablation arm only will return for additional long-term surveillance follow-up 
at 24 months post-treatment.  Evaluations to be performed will include the mean change from 
Baseline to 24 months post-treatment, as measured by the ODI, VAS, SF-36, EQ-5D-5L, as well 
as the Patient Satisfaction rating.  RF Ablation arm subjects that consent to the five-year post 
procedure follow-up sub-study will be evaluated for the mean change from Baseline to 36, 48, 
and 60 months as measured by the ODI, VAS, SF-36, EQ-5D-5L, as well as the Patient 
Satisfaction rating. 
 
7.4 
Additional Outcomes of Interest 
Additional outcomes of interest are: 
• Additional analyses of health-related quality of life and disability associated with back pain 
at baseline, 3, 6, 9, and 12 months as estimated via the EQ-5D-5L, SF-36, and ODI 
questionnaires.   
• Resource utilization and related costs associated with back pain at baseline, 3, 6, 9 and 12 
months, as estimated via treatment procedures, back pain medication usage, and national 
database statistics. 
• QALY gain for RF ablation arm and control arm, determined based on EQ-5D-5L data and 
mortality, and difference between the two strategies at various follow-up time points. 
• Incremental cost-effectiveness based on costs and QALYs for RF ablation vs. control arm. 

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8.0 
ASSESSMENT OF SAFETY 
8.1 
Safety Endpoints 
• The cumulative incidence and severity of device, procedure, neurological and spine-related 
adverse events from the treatment procedure through the final follow-up visit.  
Deterioration of neurological status will be recorded as an AE (defined as a 1-grade or 
more deficit in any motor or dermatomal sensory group). 
• The cumulative incidence of device, procedure, or spine-related SAEs and significant 
neurological events (defined as a 2-grade or more deficit in any motor or dermatomal 
sensory group) from the treatment procedure through the final follow-up visit.   
 
9.0 
DATA ANALYSIS AND STATISTICAL METHODS 
This section provides the key details of the statistical analyses to be performed. All statistical 
processing will be performed using SAS® software Version 9.2 or later unless otherwise stated. 
Multiple imputation will be used as the default method of estimating missing data for the primary 
variable.    
 
9.1 
Determination of Sample Size 
Sample size calculations for the study have been performed for the proposed primary endpoint 
assuming certain responses in each study group. Estimated responses were based on a survey of 
literature for other treatments as well as the SMART Study results. The “Two group t-test of equal 
means (unequal n’s)” option of the program nQuery Advisor Version 7.0 was used to perform the 
power computations. 
Assuming a standard deviation of 15 and a mean difference of 10 in the change from baseline for 
the ODI score, a total sample size of 75 RF Ablation and 75 Control subjects would give 
approximately 90% power for a two-sided test with an alpha level of 0.05. A randomization ratio 
of 1:1 (treated: control) was chosen to allow for an appropriate determination of the profile of the 
Control subjects. 
An assessment of the overall (ignoring treatment groups) standard deviation will be conducted at 
approximately 50% of subjects being randomized to confirm sample size and statistical power.  A 
revised sample-size may then be calculated using suitably modified assumptions. 
 
9.2 
Analysis Populations 
The primary analysis will be based upon a Modified Intent to Treat (mITT) population per the 
Food and Drug Administration E9 Statistical Principals for Clinical Trials outlined intent to treat 
principles.  Subjects will be included in the mITT population, or as otherwise defined in the 
Statistical Analysis Plan (SAP), if they meet the following criteria: 
• 
Met the primary inclusion criteria and none of the primary exclusion criteria 

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• 
Were a procedural success (for subjects in the RF ablation arm).  Procedural success is 
defined as successfully treated at the initial study procedure, as well as being a targeting 
success (appropriate ablation of the BVN) as determined by an Independent Adjudicator 
using the 6-week post-treatment MRI based on the measurements described in section 
9.6.6. 
A Per Protocol (PP) analysis will also be conducted and considered supportive.  The PP population 
is defined as all patients who were enrolled into the study and were randomly assigned to a 
treatment group and the following criteria were met: 
• 
Met the inclusion criteria and none of the exclusion criteria 
• 
Were a procedural success (for subjects in the RF ablation arm).  Procedural success is 
defined as successfully treated at the initial study procedure, as well as being a targeting 
success (appropriate ablation of the BVN) as determined by an Independent Adjudicator 
using the 6-week post-treatment MRI based on the measurements described in section 
9.6.6. 
• 
Have been compliant with the requirements of the protocol (i.e., no significant protocol 
deviations or surgical spine-related interventions) 
• 
Have completed the 6week MRI, for RF Ablation arm subjects, and 3-month follow-up 
visit for all randomized subjects. 
Have not undergone a non-study-related needle-based injection (epidural steroids, facet block, 
intradiscal procedures, etc.) for back pain prior to their 3-month follow-up visit. 
An Intent-to-Treat (ITT) analysis will also be conducted and considered supportive. The ITT safety 
population is defined as all patients who were enrolled into the study. The ITT for efficacy 
population is defined as all patients who were enrolled into the study, and were randomly assigned 
to a treatment group and the treatment was completed.  
The Safety population will be comprised of all randomized subjects.  
 
9.3 
Demographic and Baseline Characteristics 
Demographic and baseline characteristics responses will be summarized with descriptive statistics 
by treatment group and for the ITT population. Past and current medical conditions and medical 
history will not be compared statistically. 
9.4 
Primary Efficacy Analysis 
The primary efficacy endpoint of the study is the mean improvement from baseline to 3 months in 
the ODI which will be evaluated with an analysis of covariance (ANCOVA) with factors of 
treatment group and analysis center (see Section 9.6 for the definition of analysis center) and a 
covariate of baseline ODI score. The mITT analysis will be primary while the PP analysis and ITT 
analysis will be supportive. 
A conclusion of success for the primary end point will be reached (i.e., confirmation that the 
Intracept System is effective in reducing CLBP) if the mean improvement from baseline to 3 
months in the ODI is significantly greater in the RF Ablation arm than in the Control arm. 

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Multiple imputation will be the primary imputation method used to account for missing ODI 
values.  
Using a parametric regression model assuming multivariate normality and a monotone missing 
data pattern, ODI values at baseline and 3 months will be imputed.  The missing values will be 
filled in 50 times to generate 50 complete data sets. 
 
9.5 
Interim Analysis 
9.5.1 Interim Analysis 1 
Interim Analysis 1 will take place when approximately 50% of subjects have been randomized 
and have completed the 3-month follow-up. The purpose will be to conduct an inspection of the 
overall standard deviation (SD); treatment groups will not be used. If the SD is deemed too large 
to expect that the study is adequately powered, a revised sample size may be considered. 
Otherwise, Interim Analysis 2 will proceed. 
9.5.2 Interim Analysis 2 
Interim Analysis 2 may be performed when approximately 60% of subjects have been 
randomized and have completed the 3-month follow-up.  This will consist of an unblinded 
assessment of the primary analysis using the mITT population. Depending on the results of this 
analysis, the trial may stop early in case of futility, continue to full enrollment based on the 
results of Interim Analysis 1, or stop for efficacy if superiority of the treatment under study is 
clearly established.   
 
The interim analysis will be performed by an independent statistician who will report to the 
independent Data Management Committee (DMC).  The DMC will have unblinded access to all 
data and will discuss the results with the Medical Advisors and make recommendations for the 
study based on the defined stopping criteria. 
 
Full details will be provided in the Statistical Analysis Plan. 
 
9.6 
Secondary Efficacy Analyses 
Secondary efficacy analyses will be completed for the PP population as follows.  Results will be 
reported for observed data only; missing values will not be imputed.   
9.6.1 ODI 
The mean change from baseline to 3, 6, 9 and 12 months in the ODI, will be summarized by 
treatment group using descriptive statistics.  
Responder rates for ODI will be determined by the proportion of subjects who achieve ≥ 10-point 
reduction in ODI from Baseline to 3 months post-treatment.  Results will be presented for both 
treatment groups.    
9.6.2 VAS 
The mean change from baseline to 3, 6, 9 and 12 months in the VAS score will be summarized by 
treatment group using descriptive statistics.   

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Responder rates for VAS will be determined by the proportion of subjects who achieve ≥ 1.5cm 
reduction in VAS from Baseline to 3 months post-treatment.  Results will be presented for both 
treatment groups. 
9.6.3 SF-36 
The mean change from baseline to 3, 6, 9 and 12 months in the SF-36 physical component 
summary (PCS) and the mental component summary (MCS) will be summarized by treatment 
group using descriptive statistics.   
9.6.4 EQ-5D-5L 
The mean change from baseline to 3, 6, 9 and 12 months in the EQ-5D-5L will be summarized by 
treatment group using descriptive statistics.   
 
Crossover Subjects 
The above secondary end point measures will also be evaluated in the Crossover subjects post-
treatment at 3 and 6 months compared to baseline for informational purposes only.  The 12-
month Control arm visit will be considered the baseline visit for these analyses in the Crossover 
subjects.  Results will be summarized using descriptive statistics. 
 
9.6.5 Patient Satisfaction 
The Patient Satisfaction survey responses at 3, 6, 9 and 12 months post-treatment for the RF 
Ablation arm will be summarized using descriptive statistics.   
 
9.6.6 Targeting Success 
All treated vertebral body levels will be evaluated for targeting success by an independent 
radiologist.  Targeting parameters will be evaluated based on MRI data collected at six weeks post-
treatment for each of the treated subjects (RF Ablation arm and crossover subjects).   
Analysis of targeting success will consist of evaluation of the RF ablation zone location for each 
treated vertebral body as described below: 
• 
Targeting Success (hit) - Sufficient overlap of the ablation zone with the basivertebral 
foramen (BVF) in the mid-sagittal view/plane for each treated vertebral body (VB), as 
defined below, to ensure BVN ablation.   
• 
Targeting Failure (miss) - The ablation zone does not provide sufficient overlap of the 
BVF in the mid-sagittal view/plane (both the central zone and the outer ring) for 
attempted treatment of a VB. 
Images will be analyzed using suitable hardware and software in a step-wise manner as described 
below. 
1. Each VB shall be evaluated for targeting success as follows: 
i. Perform review of all 6-week post-treatment MR sequences 
ii. Measure the following: 

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i. “A” - the length of the vertebral body from the posterior wall to the anterior 
wall along the mid-sagittal plane of the BVF and parallel to the superior 
endplate.  
ii. “B” - the distance from the posterior wall to the furthest point of the ablation 
zone which intersects with the mid-sagittal plane of the BVF. 
iii. “C” – the distance from the posterior wall to the closest point of the ablation 
zone which intersects with the mid-sagittal plane of the BVF. 
iii. In the event that the BVF is not visible, either due to ablation overlap or MRI slice 
position, measurements should be taken on the mid-sagittal plane halfway between the 
inferior and superior end plates for L3, L4, and L5, and 2/3 of the way towards the 
superior end plate for S1 measurements. 
iv. Grade each VB as a “hit” or “miss” based on the overlay of the ablation zone with the 
BVF. 
 
If, on the basis of viewing T1, T2 and STIR images of sagittal and axial views, the measurements 
of A, B, and C are clearly established, a data form will be completed and the results recorded.   
Results will be reported on a “per vertebral body” and a “per patient” basis, as the percentage of 
vertebral bodies/patients. 
 
9.7 
Long-Term Surveillance Endpoint Analyses 
The additional endpoint of mean improvement from baseline to 24 months in the ODI, VAS, SF-
36, and EQ-5D-5L will be evaluated with descriptive statistics in the RF ablation arm subjects 
only.  Results for the Patient Satisfaction Survey will also be summarized. 
 
RF Ablation arm subjects that consent to the five-year post procedure follow-up sub-study will 
be evaluated for the mean change from Baseline to 36, 48, and 60 months as measured by the 
ODI, VAS, SF-36, EQ-5D-5L, as well as the Patient Satisfaction rating.  ODI, VAS, SF-36, and 
EQ-5D-5L will be evaluated with descriptive statistics.  Results for the Patient Satisfaction 
Survey will also be summarized. 
 
 
9.8 
Analysis of Additional Outcomes of Interest 
9.8.1 Health-related Quality of Life and Disability 
Additional analyses of health-related quality of life and disability will be estimated via the EQ-
5D-5L, SF-36, and ODI questionnaires.   
 
9.8.2 Costs 
Direct medical costs will be determined based on resource utilization (procedures, medications, 
hospitalizations, etc.) collected during the study and cost data obtained from published databases 
and records. 

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9.8.3 Quality-Adjusted Life Years 
Health-related quality of life data from the EQ-5D-5L and SF-36, in conjunction with mortality 
data as appropriate, will be used to compute quality-adjusted life years (QALY). 
 
9.8.4 Analyses 
Collected resource utilization and cost data will be used to assess differences between baseline and 
follow-up time points for the RF ablation and Control arms, and between the RF ablation and 
Control arms. QALYs will be computed for the RF ablation and Control arms based on collected 
EQ-5D-5L utility scores and observed mortalities. Incremental cost-effectiveness will be assessed 
using these data and model-based projections to capture longer-term time horizons beyond follow-
up observed in the trial. Further analyses might be conducted, such as exploration of potential 
indirect cost impact based on trial data and a comparison to data from the published literature. 
 
9.9 
Safety Endpoint Analyses 
Safety will be evaluated for the Safety population, which will be comprised of all ITT subjects 
who attend a follow-up visit or who through some other means provide information relating to 
their well-being.  All procedure, device, neurological and spine-related events reported in the study 
will be recorded and classified on the basis of MedDRA terminology for the Safety population.  
Reported AEs will be tabulated by subject, detailing verbatim term given by the investigator, 
preferred term, system organ class, start date, stop date, severity, and device or procedure 
relatedness.   
All reported procedure, device, neurological and spine-related SAEs will be tabulated by subject, 
detailing verbatim term given by the investigator, days from procedure to start of event, device or 
procedure relatedness, and outcome. 
All Significant neurological AEs will be tabulated by subject, detailing event description by the 
investigator, level treated, access side, start date, stop date, severity, transient or permanent 
classification, and device or procedure relatedness. 
 
10.0 
SUBJECT BENEFIT AND RISKS 
10.1 
Risks of the Intracept System 
Potential risks of the Intracept System include those of any surgical or minimally-invasive 
procedure performed with general anesthesia or moderate sedation. These risks include: 
• 
Death 
• 
Cardiopulmonary arrest 
• 
Injury to a nerve or the spinal cord leading to increased pain, numbness, 
weakness, bowel/bladder incontinence, sexual dysfunction, or paralysis. 
• 
Hypotension 

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• 
Pulmonary embolism 
• 
Pneumonia 
• 
Stroke 
• 
Bleeding sufficient to cause anemia or require transfusion 
• 
Hematoma 
• 
Pseudoaneurysm 
• 
Seroma 
• 
Blood vessel injury 
• 
Deep or superficial wound infection 
• 
Adverse reaction to medications 
• 
Treatment at wrong level 
• 
Failure to treat 
 
Potential risks from x-ray exposure used for the procedure include: 
• 
Hair loss 
• 
Cancer 
• 
Skin redness 
• 
Skin damage 
 
Potential risks specific to the Intracept System and shared with many operative or minimally–
invasive spine procedures include: 
• 
Radiculopathy 
• 
Failure to improve 
• 
Operative, peri-operative, or post-operative pain associated with or resulting 
from the procedure (including new sensation of pain or increase in 
original pain) 
• 
Thermal injury to neural, disc or paraspinal tissues 
• 
Injury to anatomical structures adjacent to the target treatment location, 
including the nerve root and spinal cord 
• 
Vertebral body fracture 
• 
Permanent nerve damage resulting in loss of function or paralysis 
• 
Device malfunction (separation of components, failure to reach target 
temperature, overheating) 
• 
Allergic reaction to device components 
All of the adverse events listed above are believed to be very rare for a procedure of this type.  As 
noted in Section 6.13, Serious Adverse Events, Significant Neurological Events, and/or other 
important clinically significant adverse events, including those that are proximate events related 
to the device or procedure, will be recorded on the CRF and reviewed by the Medical Monitor. 

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10.2 
Mitigation of Risk 
Operative and postoperative risks for the Intracept Intraosseous Nerve Ablation System and 
procedure are mitigated by: 
• Restriction of the use of the Intracept Intraosseous Nerve Ablation System to skilled spine 
surgeons and/or interventional physicians trained in the proper surgical techniques and 
imaging guidance. 
• Meticulous selection of patients using well-defined clinical and imaging criteria. 
• Careful pre-operative planning with three-dimensional imaging studies.  
• Acute and long-term clinical and imaging evaluations of treated subjects following the 
procedure.  
• Proctoring during procedures as needed. (Proctoring is performed by any clinician or by a 
Sponsor-designated physician thoroughly trained in the procedure, or by Sponsor technical 
support personnel.)  
10.3 
Risk-Benefit Analysis 
While the potential risks of the Intracept System listed in Section 10.1 are risks associated with a 
procedure of this type, review of the literature suggests that adverse events known to occur during 
transpedicular procedures or intraosseous tumor ablation procedures are rare.  Furthermore, the 
incidence of AEs in the SMART trial were within an acceptable range. 
The potential benefits of participating in this study are improvement of pain and associated 
symptoms.  Having regular, frequent interaction with the physician as part of the study may also 
be of benefit to the subject. 
The sponsor believes that the potential benefit of the Intracept procedure outweighs the risk. 
 
 
 
11.0 
STUDY OPERATIONS AND EVALUATIONS  
 
11.1 
Reporting and Recording of Data 
An electronic data capture (EDC) portal/database will be provided by the Sponsor.  The EDC 
database will be provided by a vendor with extensive clinical trial experience and will be compliant 
with FDA Code of Federal Regulations (CFR) 21 part 11 guidelines for electronic records in 
clinical trials.  All data will be entered according to the instructions provided in the CRF 
Instructions document and ICH/GCP Guidelines.   
CRFs must be completed for each subject who has provided written informed consent and begins 
Screening procedures under this protocol.  Information will be collected on potential subjects who 
screen out of the study and subjects who are enrolled.  At a minimum, the information collected 
will include date of birth and the reason the subject was not randomized. 

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The Sponsor and/or its delegate will verify the data entered into the CRFs against applicable source 
documents to ensure accuracy and completeness of the data.  Source documents for this trial may 
include, but are not limited to, hospital records, clinic records, and any study-specific worksheets, 
or laboratory result reporting documents. Data may be directly entered into CRFs, and therefore 
source documents may not be applicable to all CRF entries. Subject study records must contain 
reference to the study title and assigned subject identification number.  The signed consent form 
must be filed with the subject’s study record. 
CRF completion must be kept current to reflect subject status during the course of the trial.  No 
subject may be treated unless all Screening CRFs have been completed and submitted and the 
subject confirmed to be eligible for treatment by the study Enrollment Monitor.  
All CRF data must be reviewed by the investigator. The investigator will sign off upon completion 
of all CRFs for a subject.  
Study subjects will be identified by subject ID number.  Subject names or other personal 
identification (e.g., subject social security number) must be blacked out on any documents 
submitted to the Sponsor or their designee, with subject ID number and protocol number 
transcribed onto each document page. 
 
12.0 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL 
12.1 
Investigator Qualifications 
The investigator who performs the surgical procedure should have expertise in percutaneous, 
transpedicular vertebral body access during surgical procedures and have a lifetime history of 
having performed at least 30 kyphoplasty or vertebroplasty procedures or percutaneous pedicle 
screw placement.  All investigators who perform the surgical procedure should be fellowship-
trained and certified in the field of spine surgery by a national organization (e.g., American Board 
of Orthopedic Surgeons; American Board of Neurological Surgeons; American Board of 
Interventional Pain Physicians; American Board of Physical Medicine and Rehabilitation).  
Physician specialty types are expected to include primarily orthopedic surgeons, neurosurgeons, 
anesthesiologists, interventional neuroradiologists and physiatrists. Investigator must be willing to 
be proctored by a clinician or Sponsor designated physician trained in the procedure or by Sponsor 
technical support personnel for a minimum of 3 procedures. Deviations or exceptions to these 
investigator qualification requirements will be made on a case by case basis by the Sponsor.  
 
12.2 
Study Initiation 
Before the start of this study at each study site, the essential documents as identified in the 
Sponsor’s clinical trial SOPs must be on file in the Site Regulatory Binder as well as with the 
Sponsor or a Sponsor representative (i.e., IRB protocol and informed consent approval, 
investigator curricula vitae, investigator medical license, signed Investigator Agreement, signed 
protocol signature page, etc.).  The investigator performing the Intracept procedure must have 
completed training in the use of the device.  All site personnel must be trained on the study protocol 
and its execution, and applicable personnel must be trained on use of the EDC CRF system. 
 

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12.3 
Informed Consent 
Informed consent shall be obtained in writing and documented before a subject is enrolled in the 
clinical investigation.  It is the responsibility of the investigator to ensure that written informed 
consent is obtained from the subject and documented before any activity or procedure is 
undertaken beyond standard of care assessments and procedures. 
 
12.4 
Amendments and Deviations 
12.4.1 Protocol Amendments 
This protocol is to be followed exactly. Changes to the research covered by this protocol must be 
implemented by formal protocol amendment. Amendments to the protocol may be initiated by 
Sponsor or at the request of the investigator. In either case, a formal amendment cannot be initiated 
until it has been approved by the Sponsor and the IRB, and a protocol signature page amendment 
has been signed by the investigator. 
 
12.4.2 Protocol Deviations 
Deviation from the clinical protocol and protocol requirements must be reported to the Sponsor in 
a timely fashion.  All protocol deviations will be reviewed and evaluated on an ongoing basis and 
appropriate corrective actions implemented as necessary. 
 
12.5 
Institutional Review Board (IRB) Approval 
This study will be conducted in compliance with the Declaration of Helsinki and its amendments 
and the applicable regulations of the country in which the study is conducted. 
A properly constituted, valid IRB must review and approve the protocol, the investigator’s 
informed consent document, and related subject information and recruitment materials before the 
start of the study. 
 
12.6 
Regulatory Compliance 
The Intracept System has received FDA 510(k) clearance for the Indications for Use being studied 
under this protocol.  This study will be conducted in compliance to applicable regulations 
contained in 21 CFR 11, 50, and 56, as well as the ICH/GCP Guidelines.  The investigator and all 
research staff participating in this study are expected to adhere to this protocol, applicable privacy 
laws, and any approval requirements imposed by the Institutional Review Board. The investigator 
has the further responsibility of adherence to the Investigator Agreement and to maintain the 
contents of the Regulatory Binder. 
  
12.7 
Study Monitoring Requirements 
Study monitoring will be performed according to Good Clinical Practice (GCP), the Sponsor’s 
Standard Operating Procedures (SOPs), and the Sponsor’s Monitoring Plan. The Sponsor’s 

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Clinical Research Associates (CRA) or their delegates will conduct clinical monitoring of the 
study.  
The investigator agrees to allow these CRAs, other authorized Sponsor personnel and Sponsor 
representatives access to the treatment and clinical supplies dispensing and storage area and to 
study documentation for the above-mentioned purpose and agrees to assist the CRAs in their 
activities, as requested.  Requests by regulatory agencies to inspect the clinical site may be made. 
The investigator agrees to allow inspectors from regulatory agencies to review records and to assist 
the inspectors in their duties, if requested and as required by law.  
It is the investigator’s responsibility to ensure accurate completion of the CRFs and to approve the 
CRFs.  
 
12.8 
Case Report Forms 
Electronic CRFs will be used for this study.  The CRFs contain confidential material, and the EDC 
system will be HIPAA and 21 CFR Part 11 compliant. Specific instructions for CRF completion 
as well as CRF completion training will be provided to investigational site personnel.  
The investigator is responsible for reporting appropriately the requested information in the CRFs.  
The Sponsor and/or its delegate will verify the data entered into the CRFs against applicable source 
documents to ensure accuracy and completeness of the data. 
 
12.9 
Data Management 
The standard procedures for handling and processing records will be followed per GCP, the 
Sponsor’s (and/or their designee) SOPs, and the Sponsor’s Data Management Plan (DMP).  
 
12.10 
Disclosure of Data 
Subject medical information obtained for this study is confidential, and disclosure to third parties 
other than those noted below is prohibited.  Subject data will be identified by subject ID number 
only.  Data will be de-identified in a manner compliant with HIPAA regulations. 
Upon the subject’s permission, medical information may be given to his or her personal physician 
or other appropriate medical personnel responsible for his or her welfare. 
Data generated by this study must be available for inspection upon request by representatives of 
the FDA, national and local health authorities, the Sponsor or its designee, and the IRB for each 
study site, if appropriate. 
 
12.11 
Retention of Records 
The Sponsor requires that records and documents pertaining to the conduct of this study and the 
distribution of investigational device, including CRFs, consent form, laboratory test results, and 
study device management records, be retained by the investigator for 2 years after marketing 
application approval, or longer as required by governing local and national regulations.  If no 
application is filed, the Sponsor requires that these records must be retained for 2 years after the 

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investigation is discontinued, or longer as required by governing local and national regulations.  
The Sponsor will notify the investigator of these events. 
 
12.12 
Data Quality Assurance 
Steps to assure the accuracy and reliability of data include the selection of qualified clinical 
investigators and appropriate study sites, review of protocol procedures with the investigator and 
associated personnel prior to the study, and periodic monitoring visits by the Sponsor.  The 
Sponsor and/or its delegate will review data accuracy and completeness during and after the study, 
and any discrepancies will be resolved with the clinical investigator or designee as appropriate. 
 
 

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13.0 
APPENDIX 1: INVESTIGATOR SIGNATURE PAGE 
 
 
Title: 
A Prospective, Randomized, Multi-Center Study of 
Intraosseous Basivertebral Nerve Ablation for the 
Treatment of Chronic Low Back Pain 
Protocol Number: 
CIP 0006, REV E 
Date: 
OCTOBER 17, 2018 
 
I have received and read the protocol listed above.  I agree to undertake the protocol as defined 
therein and in accordance with the relevant parts of the ICH Guidelines for GCP, ISO 14155, the 
Declaration of Helsinki, and any other pertinent individual country laws/regulations.  I am aware 
that my adherence to the above protocol is mandatory and that any changes in the protocol or 
consent form must first be approved by the Sponsor and the Institutional Review Board, except 
those changes necessary to eliminate apparent immediate hazards to patients, or purely 
administrative changes, which must first be approved by the Sponsor.  Failure to adhere to these 
stipulations may constitute a breach of United States Federal Regulations and may result in my 
termination of the study. In addition, when applicable, we agree to enlist sub-investigators who 
also agree to perform and conduct the study as described in the protocol. 
 
 
Principal Investigator (Print Name) 
 
 
Principal Investigator (Signature) 
 
 
Date: 
 
 
 
 
 
 

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14.0 
APPENDIX 2: MAIN STUDY SCHEDULE OF ASSESSMENTS 
 
Visit or data collection 
period 
Screening 
Visit  
Baseline 
Procedure 
6 Week MRI 
3 Months Visit 
6 Months Visit 
9 Treatment 
Visit* 
12 Months 
Visit* 
24 Months 
Post-Treatment 
Visit* 
 
Timeframe 
Up to 3 
months before 
Baseline 
1-21 days 
before 
Treatment Visit 
 
6 weeks (±4 
days) after 
Treatment or 
Baseline Visit 
3 months (± 1 
week) after 
Treatment or 
Baseline Visit 
6 months (± 1 
week) after 
Treatment or 
Baseline Visit 
9 months (± 1 
week) after 
Treatment or 
Baseline Visit 
12 months (± 2 
weeks) after 
Treatment or 
Baseline Visit 
24 months (± 2 
weeks) after 
Treatment or 
Baseline Visit 
Study activities 
 
 
 
 
 
 
 
 
 
Consent 
x 
 
 
 
 
 
 
 
 
I/E criteria review 
x 
 
 
 
 
 
 
 
 
Demographics 
x 
 
 
 
 
 
 
 
 
Medical History 
x 
 
 
 
 
 
 
 
 
Review densitometry 
x 
 
 
 
 
 
 
 
 
Pregnancy test, if necessary 
x 
x 
 
 
 
 
 
 
 
BDI 
x 
 
 
 
 
 
 
 
 
Standing lateral x-ray 
x 
 
 
 
 
 
 
 
 
Review MRI 
x 
 
 
x 
 
 
 
 
 
ODI 
x 
x 
 
 
x 
x 
x 
x 
x 
VAS 
x 
x 
 
 
x 
x 
x 
x 
x 
Physical / neurological exam 
x 
x 
 
 
x 
x 
x 
x 
x 
LBP Concomitant Meds 
x 
x 
 
 
x 
x 
x 
x 
 
LBP Concomitant Therapies 
x 
x 
 
 
x 
x 
x 
x 
 
EQ-5D-5L 
 
x 
 
 
x 
x 
x 
x 
x 
SF-36 
 
x 
 
 
x 
x 
x 
x 
x 
Intracept Treatment  
 
 
x 
 
 
 
 
 
 
Patient Satisfaction 
 
 
 
 
x 
x 
x 
x 
x 
AEs 
 
 
x 
 
x 
x 
x 
x 
x 
*Post-Treatment visit to be performed in RF Ablation arm subjects only 
 
 
 

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15.0 APPENDIX 3: SUB STUDY ADDITIONAL FOLLOW-UP SCHEDULE OF ASSESSMENTS 
 
Visit or data collection 
period 
36 Months Post-Treatment Visit* 
48 Months Post-Treatment Visit* 
60 Months Post-Treatment Visit* 
 
Timeframe 
36 months (± 4 week) after Treatment  
48 months (± 4 weeks) after Treatment  
60 months (± 4 weeks) after Treatment  
Study activities 
 
 
 
Consent 
 
 
 
I/E criteria review 
 
 
 
Demographics 
 
 
 
Medical History 
 
 
 
Review densitometry 
 
 
 
Pregnancy test, if necessary 
 
 
 
BDI 
 
 
 
Standing lateral x-ray 
 
 
 
Review MRI 
 
 
 
ODI 
x 
x 
x 
VAS 
x 
x 
x 
Physical / neurological exam 
x 
x 
x 
LBP Concomitant Meds 
x 
x 
 
LBP Concomitant Therapies 
x 
x 
 
EQ-5D-5L 
x 
x 
x 
SF-36 
x 
x 
x 
Intracept Treatment  
 
 
 
Patient Satisfaction 
x 
x 
x 
AEs 
x 
x 
x 
*Post-Treatment visit to be performed in RF Ablation arm subjects who consent to participate in the Sub-study only 
 
 
 
 
 
 
 
 
 
 

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16.0 
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