Discussion
The results of this sham-controlled trial in patients with
NMOSD demonstrate that Scrambler therapy is an acceptable,
feasible, and safe intervention for central neuropathic pain, with
evidence that supports efficacy. Participants who received
Scrambler therapy had a significant reduction in pain compared
to those who received sham treatment. This was sustained at 30
days after the treatment course. Notably, there was no differ-
ence in the number of patients who thought they were assigned
to the treatment vs sham groups, which suggests that any
placebo effect was controlled for through the established sham
intervention. To date, most research investigating the effect of
Scrambler therapy on pain has involved open-label trials for
peripheral neuropathic pain management.12–15,33,34 Four
studies have used a random controlled design, including 2
unblinded prospective randomized trials that tested Scrambler
against an active comparator30,35 and 2 that have applied
a blinded randomized sham-controlled design. One involved
patients with chemotherapy-induced peripheral neuropathy,
which found no difference compared to Scrambler therapy
placed on the back near the spine (n = 14).36 In a second
prospective placebo-controlled trial in patients diagnosed with
low-back pain (n = 30), the treatment group was found to have
a significant reduction in pain compared to the control group.37
The sham group received Scrambler therapy at what was
thought to be subtherapeutic doses.
Results suggest that the trial is feasible and acceptable. Ad-
herence with the full program comprising 10 sequentialdesign to mitigate the risk of confounding effects from pain
medication class on the basis of previous data that reported
that the type of medication may be predictive of response to
Scrambler therapy,23 our study was not powered to suffi-
ciently compare efficacy results across classes of pain
medications because patients were often on multiple med-
ications. The effect that modifying pain through Scrambler
therapy had on co-occurring symptoms was also limited by
the sample size.
Lastly, while it was encouraging that a difference was detected
between the Scrambler-treated and sham arms, this study was
not powered to effectively examine sustainability of treatment
through the 60-day follow-up period. The practicality of using
Scrambler increases if the effect is sustained. The trend toward
significance at 60 days suggests that a larger study that
includes 29 patients per arm may uncover sustained effect.
Furthermore, re-emergence of pain in treatment of both
central and peripheral pain conditions has been described,18,19
and pain has been shown to be amenable to subsequent
booster treatments, often with fewer Scrambler treatment
sessions needed.12 Anecdotally, 1 complete responder from
the current study was subsequently treated when pain began
to re-emerge after study completion and remains pain-free
months later. Thus, adapting the protocol to include sub-
sequent booster treatments when pain emerges should be
considered for future studies. Overall, the effectiveness, fea-
sibility, and safety profiles we report support the need for
a larger phase III study to further examine the effect of
Scrambler on pain, reduction of analgesic medication use, co-
occurring symptoms, and QoL in a larger NMOSD patient
cohort.
News 
Market Data 
Discover 
