The HALO Study: The Pain Supressive Effect of Low Frequency Spinal Cord Stimulation versus High Frequency Spinal Cord Stimulation

Rationale: Electrical stimulation of the dorsal columns of the spinal cord
(Spinal Cord Stimulation or SCS) for pain relief has been used in humans for
several decades. The most common indication for SCS is the treatment of
refractory neuropathic leg pain, particularly when these symptoms persist after
an anatomically successful operation (Failed Back Surgery Syndrome or FBSS).

Low frequency * conventional - SCS (LF-SCS) is applied in frequencies ranging
from 30Hz to 100 Hz and the subject feels paraesthesias in the painful area,
which is considered the ideal situation. Recently, LF-SCS has been challenged
by the development of stimulation modes at higher frequencies which provide
pain relief at sub-perception threshold, i.e. without paraesthesias. A recent
case series reported that High Frequency Spinal Cord Stimulation (HF-SCS) with
frequencies ranging fromo 500- 10 000Hz, appears to show better pain relief for
both back and limb pain in comparison to LF-SCS, and also to be effective in
some subjects who did not respond to LF-SCS.

We propose a study to compare the pain supression of Low Frequency SCS
(LF-SCS) with High Frequency SCS (HF-SCS) in an double blind, randomized,
controlled, crossover study.

The primary objective of this study is to compare pain suppression in two
groups of subjects with chronic unilateral limb pain as a result of FBSS. Low
Frequency spinal cord stimulation settings and High Frequency spinal cord
stimulation settings will be compared to the baseline pain scores (Visual
Analogue Scale).

A prospective, double blind, multi-centre, randomized, crossover study of SCS
in the treatment of subjects with refractory neuropathic leg pain after back
surgery. 30 subjects will be included and divided over 5 centres. Subjects will
be randomized on a 1:1 basis to either the LF or the HF group, and will cross
to the other group after a wash-out period.

All subjects will be stimulated with both standard forms of spinal cord
stimulation: Low Frequency (LF-SCS) at 30Hz and High Frequency (HF-SCS) at
1000Hz, with the same SCS device, for 9 (+3) days and then enter a five day
wash-out period before transferring to the other arm of the study. The order in
which they receive the therapy will be determined by the blinded randomization
procedure.
At the end of the trial period, positive responders will be implanted with an
internal pulse generator (IPG), according to their preference of stimulation
and will be followed-up for 1 year according to standard care, as outlined by
the Dutch Neuromodulation Society, on which this protocol is based.
Non-responders, (expected to be up to 10% of subjects), will have the hardware
removed and will not be followed up regarding the secondary endpoints.

Both methods of stimulation are standard clinical practice performed routinely
in the study centres; there is therefore no extra risk to the subjects. The
protocol is based on the standard care and post-operative follow-up of SCS
subjects as proposed by the Dutch Neuromodulation Society. Both groups will
receive this standard care. The only difference is change of stimulation
frequency. There is therefore no extra physical risk to the patient.
The duration of the trial-period falls within the generally accepted period of
30 days for trial stimulation. This trial will end after 23 (+6) days including
both trial phases and the wash-out period. During the trial period, subjects
may use escape medication. There is therefore no extra burden to the subject.
Possible benefit to the subject is that both forms of stimulation will be
evaluated. This may lead to a better quality of life in the HF-SCS Group as
result of pain relief without paraesthesias. Furthermore, non-responders to
LF-SCS may benefit from HF-SCS. Standard follow-up care and protocolled
post-operative procedures will be followed in both study groups