Subcutaneous Stimulation as Add on Therapy to SCS toTreat Low Back Pain in FBSS

Aim of the study FBSS is a clinical entity consisting of chronic leg and /or back pain due to radicular nerve damage. The effectiveness of SCS in the pain management of patients with FBSS is proven. Patients mostly have dominant leg pain, however a significant percentage of FBSS patients has a more pronounced back pain and are commonly excluded from SCS as it is often inadequate in relieving both the back and leg pain components. Recently some reports showed the benefit of subcutaneous stimulation (SubQ) for low back pain in patients with FBSS. This has been confirmed by a feasibility study performed by our group. The aim of the randomized controlled study is to evaluate the effect of SubQ on low back pain in FBSS patients for whom SCS gives an inadequate back pain relief.

Hypothesis We hypothesize that SubQ in addition to SCS in FBSS patients with leg and low back pain is more effective in treating low back pain (i.e. >50% pain reduction) than SCS alone.

Study design and duration of the study The study is a randomized controlled trial. Patients with FBSS with additional chronic back pain and an intensity of 5 or more for leg and back pain separately on the visual analogue scale are eligible for the study. About ninety patients will receive a SCS system targeting to relief leg and back pain. The study group consists of patients having a pain reduction of ≥50% in the leg after SCS trial stimulation. If, after trial stimulation, there is less than 50% back pain relief compared with initial values, patients will receive one or two Quad leads subcutaneously at the time of implantation of the pulse generator.

This group, a total of 56 patients,will be randomized in a 1:1 ratio in which group 1 (n=28) receives SCS plus non-activated SubQ(SubQ OFF) and group 2 (n=28) receives SCS plus activated SubQ (SubQ ON) (phase 1), for a period of 3 months.

After the controlled phase of the study, all 56 patients will receive maximal effective SCS and SubQ for the rest of the study duration (phase 2).

Total duration of the study for a patient is12 months. Estimated duration of the study is 18 months.

Comparisons will be made after 3 months between no SubQ OFF and SubQ ON. After 6 and 12 months (phase 2) patients will be compared with their baseline values to explore long term effects of SCS and SubQ.

Type and number of patients The study will include FBSS patients with leg and low back pain, failing to relief back pain with SCS. For the controlled part of the study 56 patients are needed based on a power calculation in which a difference between the two treatments is postulated of about 40%. To assure this about 90 patients will be included in the study.

Inclusion criteria Male/female > 18 and < 75 years Chronic neuropathic pain secondary to FBSS Pain radiating in lumbar segments L4 and/or L5 and/or S1 for at least 6 months Pain intensity assessed by VAS ≥ 5 scored separately for leg and back Willing to provide informed consent Exclusion criteria Presence of any other clinically significant or disabling chronic pain condition Expected inability of patients to properly operate the neurostimulation system History of coagulation disorders, lupus erythematosus, diabetes mellitus, rheumatoid arthritis or morbus Bechterew Active malignancy Current use of medicines affecting coagulation which cannot be temporarily stopped Evidence of an active disruptive psychiatric disorder or other known condition significant enough to impact the perception of pain, compliance to intervention and/or ability to evaluate treatment outcome as determined by the investigator Life expectancy of less than 1 year Existing or planned pregnancy Study therapy test therapy: Adequate subcutaneous stimulation with perceived paresthesias in the painful area in the back reference therapy: SCS plus non-activated SubQ (SubQ OFF) Parameters for evaluation of effectiveness primary outcome: The proportion of patients with SCS plus activated SubQ and SCS without activated SubQ having 50% or more pain relief(responder rate) in back after 3 months of stimulation, assessed with the VAS.

secondary outcomes:

Effect of SCS plus activated SubQ and SCS without activated SubQ after 3, 6 and 12 months on:

Mean reduction in pain intensity for leg and back pain separately, assessed by the VAS Responder rate of SCS on leg pain assessed by the VAS Responder rate of SubQ on back pain assessed by the VAS(after 6 and 12 months) Quality of life assessed by Short Form 36 (SF-36) Quality of life as assessed by EuroQuol (EQ-5D) Function assessed by the Oswestry disability index Patient satisfaction assessed by the Global Impression of Change (GPIC) Pain assessed by the McGill questionnaire Concomitant drug treatment for relief of pain Concomitant need for physical therapy or other non-drug treatment. Employment status Frequency and nature of adverse events

And in addition after 12 months of stimulation, on:

Cost-utility Preferred stimulation settings