Cryoneurolysis Outcome on Pain Experience (COPE) in Patients With Low-back Pain

Background: Low-back pain, including facet joint pain, accounts for up to 20 percent of all sick leaves in Denmark; among these are patients with facet joint pain syndrome. A proposed treatment option is cryoneurolysis. This study aims to investigate the effect of cryoneurolysis in lumbar facet joint pain syndrome

Methods: A single-center randomized controlled trial (RCT) is performed including 120 participants with chronic facet joint pain syndrome, referred to the Department of Neurosurgery, Aarhus University Hospital. Eligible patients receive a diagnostic anesthetic block, where a reduction of pain intensity >50 % on a numerical rating scale (NRS) is required to be enrolled. Participants are randomized into three groups to undergo either one treatment of cryoneurolysis, radiofrequency ablation or placebo. Fluoroscopy and sensory stimulation is used to identify the intended target nerve prior to administrating the above-mentioned treatments. All groups receive physiotherapy for 6 weeks, starting 4 weeks after treatment. The primary outcome is a reduction in low-back pain intensity and an impression of change in pain after intervention (Patient Global Impression of Change (PGIC)) at 4 weeks follow-up, prior to physiotherapy. Secondary outcomes are quality of life (EQ-5D, SF-36) and level of function (Oswestry Disability Index), psychological perception of pain (Pain Catastrophizing Scale) and depression status (Major Depression Inventory). Data will be assessed at baseline (T0), randomization (T1), day one (T2), 4 weeks (T3), 3 (T4), 6 (T5) and 12 months

• Cryoneurolysis (Procedure), also known as cryoanalgesia, cryoneuroablation: This is a medical procedure that temporarily blocks nerve conduction along peripheral nerve pathways by freezing it. Small probe is inserted in order to freeze the target nerve, can facilitate complete regeneration of the structure and function of the affected nerve.
• Radiofrequency ablation (Procedure): This is a medical procedure that temporarily blocks nerve conduction along peripheral nerve pathways. Small needle with an active heating tip is inserted, to destroy the functionality of the target nerve using heat from radiofrequency energy.
• Placebo (Procedure): No active treatment is given.

Primary outcomes

• The effect of the intervention, assessed by Patient Global Impression of Change (PGIC) at 4 weeks follow-up [4 weeks]: The Patient Global Impression of Change (PGIC) is a 7-point patient self-reporting scale of overall improvement after treatment ranging from 1) very much improved, 2) much improved, 3) minimally improved, 4) no change, 5) minimally worse, 6) much worse, or 7) very much worse

Secondary outcomes

• Change in Patient Global Impression of Change (PGIC) at day one, three, six and 12 months follow-up. [1-12 months]: The Patient Global Impression of Change (PGIC) is a 7-point patient self-reporting scale of overall improvement after treatment ranging from 1) very much improved, 2) much improved, 3) minimally improved, 4) no change, 5) minimally worse, 6) much worse, or 7) very much worse.
• Change in the Numeric Rating Scale (NRS-11) from baseline to day one, four weeks, three, six and 12 months follow-up [1-12 months]: The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain from 0 no pain to 10 worst pain imaginable.
• Change in the Pain Catastrophizing Scale (PCS) at baseline, four weeks, three, six and 12 months follow-up [1-12 months]: The Pain Catastrophizing Scale (PCS) assesses the extent of catastrophic thinking due to low back pain according to 3 components: rumination, magnification, and helplessness. It is a self-report measure, consisting of 13 items scored from 0 to 4, resulting in a total possible score of 52. The higher the score, the more catastrophizing thoughts are present.
• Change from baseline to six and 12 months follow-up in the Oswestry Disability Index (ODI). [1-12 months]: The Owestry Disability Index (ODI) comprises 10 sections with 5 questions in each to measure a patient's permanent functional disability. For each section the scores range of 0 to 5, resulting in a total possible score of 50. If all 10 sections are completed the score is calculated as follows: if 16 (total scored) out of 50 (total possible score) x 100 = 32%. The higher the calculated percentage, the more severe the disability is.
• Change from baseline to six and 12 months follow-up in the European Quality of Life - 5 Dimensions (EQ5D) [1-12 months]: The European Quality of Life - 5 Dimensions (EQ5D) comprises five questions on mobility, self care, pain, usual activities, and psychological status with three possible answers for each item (1=no problem, 2=moderate problem, 3=severe problem. A summary index with a maximum score of 1 can be derived from these five dimensions by conversion with a table of scores. The maximum score of 1 indicates the best health state, in each dimension, where higher scores indicate more severe. In addition, there is a visual analogue scale (VAS) to indicate the general health status with 100 indicating the best health status.
• Change from baseline to 12 months follow-up for change in Major Depression Inventory (MDI) and the Short Form (36) Health Survey (SF-36) [1-12 months]: The Major Depression Inventory (MDI) is a self-reporting measure to assess the presence and severity of a depressive disorder. It consists of 10 questions with a total possible score of 50. A score of under 20 indicates no depression and a score of more than 29 indicates severe depression. The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. it consists of 8 scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability while higher scores indicate the less disability .The maximum score of 100 indicates the best possible health state.

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Low-back pain from facet joint syndrom (facet joint pain) > 3 months' duration with or without neuropathic pain component.
* Low-back pain on Numeric Rating Scale ≥ 4

Exclusion Criteria:

* Presence of nerve root or spinal canal compression; signs of inflammatory or erosive processes in the spine verified on magnetic resonance imaging (MRI).
* Neurological deficits i.e. symptoms of nerve root compression; tingling, numbness, weakness/ paresis, and reflex loss in the lower extremities.
* Major co-morbidity.
* Anti-thrombotic or anti-platelet treatment which cannot be paused for a week.
* Active malignancies.
* Chronic inflammatory disease.
* Known severe psychiatric disease. Patients with mild and well-treated depression and anxiety are not excluded.

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• Kaare Meier, MD, Ph.D, Study director, University of Aarhus
• Lone Nikolajsen, M.D, Prof., Study director, University of Aarhus
• Maurits Van Tulder, Prof., Study director, University of Aarhus
• Jens Christian H Sørensen, M.D, Prof., Study director, University of Aarhus