A Prospective, Single-center, Pilot Study of in Vivo Lesion Characteristics Post Coolief Cooled Radiofrequency Denervation as a Treatment for Chronic Pain
Phase: NA
Conditions: Arthritis;Lumbosacral, Osteo Arthritis Knee, Sacroiliitis, Hip Osteoarthritis, Arthritis, Degenerative
Sponsor: International Spine, Pain and Performance Center

 
 
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Clinical Study Protocol 
 
Protocol Title: 
A Prospective, Single-center, Pilot study in vivo lesion characteristics post  
Cooled Radiofrequency Denervation as Treatment for Chronic Pain.  
Protocol #: 
105-17-0004 
Study Short Name: 
MRI Exploration study 
Country: 
North America 
Indications:  
Pain Management; Chronic Pain that can be treated with Radiofrequency 
ablation. 
Sponsor: 
Mehul Desai, MD/Puneet Sayal, MD 
International Spine, Pain and Performance Center  
 
Washington, DC Site 
2141 K Street, NW, Suite 600 
Washington, DC 20037 
 
Arlington, VA Site 
1635 North George Mason Drive, Suite 180 
Arlington, VA 22205 
 
Attn: [Puneet Sayal] [202-808-8295] 
Current Protocol Version: 
V 2.0 24 May 2018 
Initial Protocol Version: 
V 1.0 17 January 2018 

 
 
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General Information 
 
Print 
Signature 
Study Director 
Mehul Desai, MD/Puneet Sayal, MD 
International Spine, Pain and 
Performance Center 
 
Washington, DC Site 
2141 K Street, NW, Suite 600 
Washington, DC 20037 
 
Arlington, VA Site 
1635 North George Mason Drive,  
Suite 180 
Arlington, VA 22205 
 
 
Radiologist: 
Yair Safriel, MD 
601 Main Street 
Dunedin, FL 34688 
(727) 733-1111  
 
 Study Coordination:  Sidrah Sheikh 
2141 K Street NW, Suite 600 
Washington, DC 20037 
 
 
 
 
 

 
 
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1 
Synopsis 
Protocol Title: 
A Prospective, Single-center, Pilot study to determine in vivo lesion 
characteristics post Cooled Radiofrequency Denervation  
Test Article(s): 
MRI characteristics of lesions post-radiofrequency ablation 
Planned Number of Sites: 
1 
Planned Number of Subjects: 
Up to 15 
Study Design: 
Prospective, Single-center, Human, Interventional 
Study Duration: 
Individual Study Participation: Up to 7 days post treatment  
Objectives: 
The primary objective of this protocol is to quantify CRFA lesion size 
on MRI post CRFA treatment. 
Eligibility Criteria: 
Inclusion Criteria       
1. Age ≥ 21 years 
2. Able to understand the informed consent form and provide 
written informed consent and able to complete outcome 
measures. 
3. Must be clinically appropriate candidate to receive CRFA for 
treatment of chronic pain.  
4. Willing and able to receive an MRI  
 
Exclusion Criteria 
1. Unable to receive an MRI (i.e. due to pacemaker, iron-based 
metal implant, allergy to contrast medications utilized). 
2. Extremely thin patients and those with minimal subcutaneous 
tissue thickness that would not accommodate a 
radiofrequency lesion of up to 14mm in diameter to limit the 
risk of skin burns.  
3. Active joint infection or systemic or localized infection at the 
needle entry site (subject may be considered for inclusion 
once infection is resolved.) 
4. Subject currently implanted with a pacemaker or defibrillator 
5. In the event a pre-treatment MRI is obtained, trauma or injury 
occurring to the targeted area between the baseline MRI and CRFA 
treatment  
6. Subject unwillingness or unable to comply with protocol 
requirements 
 
 
 
 

 
 
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Table of Contents 
General Information 
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2 
List of Abbreviations and Definition of Terms 
Abbreviation 
Definition 
CRFA 
Cooled Radiofrequency Ablation 
IRB 
Institutional Review Board 
MRI 
Magnetic resonance imaging 
PI 
Principal Investigator 
RF 
Radiofrequency 
SI 
Sacroiliac  
SIJ 
Sacroiliac Joint 
 
3 
Introduction 
3.1 
BACKGROUND / STUDY POPULATION 
 
Chronic back and hip pain is a leading cause of morbidity in an aging population. Sources of pain are 
highly variable and multiple treatment options exist including physical therapy, medications, injections, 
radiofrequency, PRP and ultimately surgery. 
 
Cooled Radiofrequency ablation (CRFA) is a well-established method for delivering lesions into 
nervous tissue to accomplish neurotomy procedures.  Multiple references exist in the literature noting 
the clinical outcomes of patients treated with CRFA cooled radiofrequency for pain managing 
denervation in other anatomic locations, including the sacroiliac joint1,2,3,4, the lumbar spinal disc.5,6,7 
and recent human studies have started to demonstrate the effects of CRFA when specifically used for 
                                                     
1 
2 
3 
4 
5 
6 
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genicular neurotomy procedures in patients with chronic knee pain resulting from conditions such as 
osteoarthritis8.   
3.2 
RATIONALE FOR STUDY 
 
This Prospective, Single-center, Pilot Study will assist in gaining an understanding of the actual CRFA 
lesions in an in vivo situation in areas where CRFA is utilized as a standard of care treatment option 
for the relief of chronic pain (cervical facet joints, thoracic facet joints, lumbar facet joints, Sacroiliac 
(SI) region, hip and knee). The primary rationale is to better quantify lesion properties in order to 
ensure procedural optimization. The study does not introduce any experimental procedures as the 
product will be used in a manner that is consistent with their labeled indications. 
3.3 
POTENTIAL RISKS & BENEFITS  
 
Because radiation is not used, there is not risk of exposure to radiation during an MRI procedure. 
However, due to the use of the strong magnet, MRI cannot be performed on patients with: 
 
● 
Implanted pacemakers 
● 
Intracranial aneurysm clips 
● 
Cochlear implants 
● 
Certain prosthetic devices 
● 
Implanted drug infusion pumps 
● 
Neurostimulators 
● 
Bone-growth stimulators 
● 
Certain intrauterine contraceptive devices;  
● 
Any other type of iron-based metal implants 
● 
Allergies to contrast medications such as Gadolinium based contrast agents (GBCA) 
especially in patients with renal and/or kidney impairment.  
 
MRI is also contraindicated in the presence of internal metallic objects such as bullets or shrapnel, as well 
as surgical clips, pins, plates, screws, metal sutures, or wire mesh. The use of GBCA is reason for 
serious concern with regards to the MRI procedure. Nephrogenic systemic fibrosis (NSF) has been linked 
to the use of GBCA in conjunction with MRI, specifically in patients with the following renal impairments:  
● 
Acute Kidney injury 
                                                     
8 

 
 
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● 
End-stage renal disease 
● 
Stage 4 & 5 chronic kidney disease  
 
Complications due to GBCA in renally impaired patients can manifest themselves in the following 
ways:  
● 
Hyperpigmentation 
● 
Yellow papules and/or plaques 
● 
Blistering 
● 
Ulceration 
The results of such presentations include sever pruritus, paraesthesia, as well as pain, and flexion 
contractures that begin on the appendages and extend proximally10.  
 
 
If you are pregnant or suspect that you may be pregnant, you should notify your physician before 
receiving an MRI. 
4 
Study Objectives and Purpose 
 
The primary objective of this protocol is to collect MRI data post CRFA treatment. 
5 
Investigational Plan 
5.1 
  STUDY DESIGN   
 
This study will be a prospective, single-center, pilot study. Adult subjects over the age 21 diagnosed with 
chronic joint pain (≥ 3 months), scheduled to receive Radiofrequency denervation and meet the selection 
criteria are eligible to participate in this study. The specific targeted areas of interest in this study will 
include Cervical facet joints, Thoracic facet joints, Lumbar facet joints, Sacroiliac (SI) region, hip and 
knee.  
 
The treating physician will follow Standard of Care treatment for all enrolled subjects. As illustrated in 
Figure 1, the study consists of a screening visit, a treatment visit and a follow up visit. All subjects 
receiving CRFA will receive an MRI 2 – 7 days after the CRFA procedure. Subjects receiving CRFA of 
the Sacroiliac Joint will also receive an MRI within 30 days prior to the CRFA procedure. The treating 
physician may also request an MRI be performed prior to the procedure for subjects receiving CRFA of 
other targeted areas. The point of enrollment for each subject is the time that they sign the Informed 
Consent Form.  
 

 
 
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MRI data will be reviewed by the radiologist on a per patient basis to confirm lesion characteristics. It is 
anticipated that 3-5 subjects per level will be needed to fully quantify lesion characteristics, however; 
enrollment will remain flexible for each targeted area based on real time review of MRI data. 
 
Figure 1: Study Design 
Visit 1: Screening  
Pre - MRI (if applicable) 
  
Visit 2: CRFA 
Treatment Visit (Day 
0) 
  
Visit 3:  
MRI 2-7 days 
post treatment 
  
  
  
  
 
  
  
  
  
  
  
  
  
  
  
CRFA = Cooled Radiofrequency Ablation procedure 
5.2 
ENDPOINTS 
5.2.1 
PRIMARY ENDPOINT 
 
Quantifiable MRI data of CRFA lesion. 
5.3 
MEASURES TO MINIMIZE / AVOID BIAS 
 
An independent radiologist will review MRI data, Dr. Yair Safriel. 
5.4 
DURATION OF SUBJECT PARTICIPATION 
 
The screening period could take up to 30 days to complete for all subjects. Subjects will participate in 
the study through receipt of their MRI (approximately 10 days from the time of the procedure).  
5.5 
STUDY-STOPPING CRITERIA 
 
Post procedure MRI for each targeted area will be reviewed in real time. This will allow for analysis of 
the MRI by modality. Each targeted area will be reviewed independently and collectively and the study 
may be terminated at any time once MRI data collected is adequate to quantify lesion characteristics. 
Additionally, enrollment adjustments may be made for each area independently based on information 
received.                                                                                                                                                                                      
The study may also be terminated if the sponsor determines that there is a clinical or other reason to 
do so. In the event the study is stopped, subjects already enrolled will be followed according to the 
protocol and recruitment will be stopped. Potential reasons for early termination may include (but are 
not limited to): 

 
 
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● 
Stopping for success following interim analysis 
● 
Stopping for futility following interim analysis 
● 
Administrative reasons 
 
5.6 
  TREATMENT ASSIGNMENT / RANDOMIZATION  
 
There is no randomization performed in this study. All eligible and enrolled subjects will receive 
Radiofrequency Treatment per Standard of Care. The MRIs will be conducted per standard of care 
within the windows detailed in this protocol.   
6 
Subject Selection 
 
Subjects will include individuals who are scheduled to receive Cooled RF treatment as part of their 
Standard of Care for their condition/disease state. Subjects will be required to sign informed consent 
for the MRI and to allow data to be utilized for research.  
6.1 
INCLUSION CRITERIA: 
 
1. Age ≥ 21 years 
2. Able to understand the informed consent form and provide written informed 
consent and able to complete outcome measures. 
3. Must be clinically appropriate candidate to receive CRFA for treatment of chronic 
pain.  
4. Willing and able to receive an MRI  
6.2 
EXCLUSION CRITERIA: 
 
1. Unable to receive an MRI (i.e. due to pacemaker, iron-based metal implant or 
allergies to contrast medications utilized). 
2. Extremely thin patients and those with minimal subcutaneous tissue thickness 
that would not accommodate a radiofrequency lesion of up to 14mm in diameter 
to limit the risk of skin burns.  
3. Active joint infection or systemic or localized infection at the needle entry site 
(subject may be considered for inclusion once infection is resolved.) 
4. Subject currently implanted with a pacemaker or defibrillator 

 
 
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5. In the event a pre-treatment MRI is obtained; trauma or injury occurring to the 
targeted area between the baseline MRI and CRFA treatment  
6. Subject unwillingness or unable to comply with protocol requirements 
 
7 
Study Procedures  
7.1 
CENTER READINESS 
 
Prior to initiating study procedures, all applicable regulatory requirements must be fulfilled. Each study 
site must have written documentation of readiness including but not limited to:  
● 
Investigational Review Board (IRB) approval of the current version of the Clinical Investigation 
Plan (Protocol) and Informed Consent Form (ICF) or waiver obtained indicating IRB oversight 
is not required  
● 
Signed/dated Curriculum Vitae and current medical licensure for Investigator and Sub-
Investigator(s) 
● 
Signed/dated Financial Disclosure Forms for Investigator and Sub-Investigator(s) 
 
7.2 
INFORMED CONSENT PROCEDURES 
 
Prior to undergoing any study procedure or baseline testing, each subject must indicate their consent 
by signing and dating the current IRB-approved Informed Consent Form.  Consent forms must be 
approved by the IRB prior to implementation and must be provided to the subject in their primary 
language complying with the requirements of 21 CFR 50. 
Adequate time should be provided for subjects and/or legally authorized representatives (LARs) to 
review the consent form and ask any questions.  The subject should receive a copy of the 
signed/dated consent form for their records.  Information detailing the Informed Consent process must 
be clearly documented in each subject’s medical/study record (source document).  
7.3 
MEASURES AND METHODS OF ASSESSMENT 
 
The following assessments will be utilized throughout the study in accordance with the assessment 
schedules described below. 

 
 
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7.3.1 
SCHEDULE OF ASSESSMENTS 
 
Table 1: Schedule of Assessments 
 
  
V1 
V2 
V3 
Screening  
 
Index Procedure / 
Treatment  
(DAY = 0) 
MRI 
Procedure 
Within 30 Days of 
ICF 
 Within 30 Days of 
Screening 
2-7 days  
post treatment 
Informed Consent 
X 
  
  
Inclusion/Exclusion 
X 
X 
  
 (CRFA) Applications 
  
X 
  
MRI (SI patients only) 
X  
 
X 
 
7.3.2 
DEMOGRAPHIC INFORMATION 
 
Age, gender, race, BMI, treatment history, comorbidities, and concomitant medications will be 
collected for demographic analysis.  
7.3.3 
MRI INFORMATION 
 
Ideal conditions for MRI are described below:  
- 
RF entry points should be marked on the scan with MRI compatible markers at the time of scan. 
- 
All axial images should be a stack (not angled to disc or any other structures). 
- 
All slices should be 3mm thick with a gap of no more than 0.3mm through the area of RF. 
- 
Post contrast imaging would be ideal. 
- 
Axial and sagittal post contrast T1 fat suppressed (Dixon suppression, if possible on all subjects) 
- 
T2 based imaging should be both axial and sagittal. Ideally, preference towards T2 fat 
suppression/T2FS (Dixon suppression, if possible on all subjects) in both planes. 
- 
Should have STIR on all studies as well in both planes. 
- 
If time/cost does not permit both T2FSand STIR, default to STIR only. If no post contrast imaging, 
should really have both STIR and T2FS. 
 
8 
Procedures by Visit 
8.1 
Visit 1 - Screening 
 

 
 
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1. Perform standard of care work up to ensure potential patient is an appropriate 
candidate to receive CRFA in one of the targeted areas identified within this study 
2. Subject Selection / Informed Consent 
3. Schedule and Perform MRI of treatment area (if applicable) 
4. Schedule Treatment visit within 30 days of ICF  
8.2 
Visit 2 - Index Treatment (Day 0) 
 
1. Verify that subject continues to meet all eligibility criteria. 
2. Perform CRFA procedure per standard of care 
8.3 
Visit 3 - (2-7 days post procedure) 
 
1. Perform MRI of treatment area. 
8.4 
Discontinuation / Early Termination (ET)  
 
Subjects may withdraw from the study at any time for any reason.  Early terminations can occur under 
the following circumstances: 
1. Subject Withdraws Consent 
2. Investigator withdraws the subject for any reason following discussion with the sponsor 
3. Investigator withdraws the subject immediately for emergent safety issue and reverts to 
institutional standards-of-care 
4. Subject becomes Lost-to-Follow up (LTF) 
 
 
The study may be terminated by the investigator at any time for any reason.  This could include the 
situation where consistency in lesion characteristics is identified across treatment areas. If a subject is 
withdrawn or the study is terminated, investigators will continue to treat per institutional standard of 
care procedures. 
9 
Adverse Event Reporting 
9.1 
ADVERSE EVENTS (AE) ASSESSMENT 
 
Adverse Events will be managed and treated per Standard of Care.  
10 
Statistical Methods and Data Analysis 
 

 
 
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Data collected within this protocol will be reported utilizing descriptive statistics.  
10.1 
STUDY SUBJECTS 
 
Sample size requirements are estimated and depending on quality of imaging returned, fewer patients 
may be needed within each targeted area. Image analysis will happen in real time in an effort to confirm 
when sufficient data exists for each targeted area. Additionally, if consistency in lesion characteristics is 
identified across treatment areas, the study could be stopped before estimated enrollment is complete.  
10.2 
PRIMARY EFFICACY PARAMETERS 
 
MRI imaging review containing the ability to quantify the lesion being created.  
10.3 
DEMOGRAPHICS, BASELINE CHARACTERISTICS, AND CONCOMITANT MEDICATIONS 
 
Demographic data, medical history, and concomitant medications will be summarized by means of 
descriptive statistics (number, mean, SD, median, minimum, and maximum) or frequency tables. 
10.4 
EFFICACY ANALYSES (MAY BE CHANGED AS NEEDED FOR CONSUMER STUDIES) 
10.4.1 PRIMARY EFFICACY ANALYSIS 
 
No efficacy analyses will be performed in this study.  
11 
Ethical, Administrative, and Regulatory Obligations 
11.1 
INDEPENDENT ETHICS COMMITTEE (IEC) OR INSTITUTIONAL REVIEW BOARD (IRB) 
 
The study protocol, ICF document(s), and any amendments must be submitted to and approved by the 
IRB/IEC prior to enrolling subjects.  The IRB must be operating in compliance with 21CFR Part 56.  
11.2 
HEALTH INSURANCE PORTABILITY AND ACCOUNTABILITY ACT (HIPAA) 
 
In accordance with the Health Insurance Portability and Accountability Act (HIPAA) of 1996, the 
Investigator must obtain authorization from the patient to use and/or disclose protected health 
information (PHI).  HIPAA authorization may be obtained as part of the ICF or in a separate document. 
HIPAA authorization must include: 
A. 
Identification of the parties that can use and disclose the PHI 
B. 
Identification of the parties to whom the PHI may be disclosed 

 
 
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C. 
A meaningful description of the PHI 
D. 
A description of each purpose for the use and disclosure 
E. 
Information about the subject’s rights related to the authorization 
F. 
Information about the expiration of the authorization 
G. 
Instructions on how to revoke the authorization 
H. 
A statement about what may happen if the authorization is not signed 
I. 
A warning that once information has been released, it may be released again without 
further authorization 
12 
Records Retention and Archival 
Study records must be maintained per requirements outlined in 21 CFR 812.140. 
13 
References 
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Medicine 2010; 11(1): 53–57 
2 Patel N, Gross A, et al. A randomized, placebo controlled study to assess the efficacy of lateral branch denervation for chronic sacroiliac joint pain. Pain Med 
2012 Mar; 13(3):383-98. 
3 Stelzer W, Aiglesberger M, Stelzer D, et al.  Use of Cooled Radiofrequency Lateral Branch Neurotomy for the Treatment of Sacroiliac Joint-Mediated Low Back 
Pain: A Large Case Series.  Pain Medicine 2013 Jan: 14(1):29-35. 
4 Ho, KY, Hadi MA, Pasutharnchat K, et al.  Cooled radiofrequency denervation for treatment of sacroiliac joint pain: two-year results from 20 cases.  J Pain 
Research 2013; 6(2):505–511. 
5 Kapural L, Mekhail N.  Novel intradiscal biacuplasty (IDB) for the treatment of lumbar discogenic pain.  Pain Pract 2007 Jun; 7(2):130-4. 
6 Karaman H, Tufek A, Kavak GO, et al.  6-month results of TransDiscal Biacuplasty on patients with discogenic low back pain: preliminary findings.  Int J Med Sci 
2010 Dec 14; 8(1):1-8. 
7 Kapural L, Vrooman B, Sarwar S, et al.  A randomized, placebo-controlled trial of transdiscal radiofrequency biacuplasty for treatment of discogenic lower back 
pain.  Pain Med. 2013 Mar; 14(3):362-73. 
8 Davis, et al, RAPM 2017, In Press /FDA clearance K163461 
9 Davis, et al. Abstracts and Highlight Papers of the 36th Annual European Society of Regional Anaesthesia & Pain Therapy (ESRA) Congress 2017, Regional 
Anesthesia & Pain Medicine: September/October 2017 - Volume 42 - Issue 5S - p e1–e200 
10 Khawaja, Aurang Z., et al. “Revisiting the Risks of MRI with Gadolinium Based Contrast Agents—Review of Literature and Guidelines.” Insights into Imaging, 
vol. 6, no. 5, 2015, pp. 553–558.