Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial

Abstract

Background: Painful conditions such as residual limb pain (RLP) and phantom limb pain (PLP) can manifest after amputation. The mechanisms underlying such postamputation pains are diverse and should be addressed accordingly. Different surgical treatment methods have shown potential for alleviating RLP due to neuroma formation - commonly known as neuroma pain - and to a lesser degree PLP. Two reconstructive surgical interventions, namely targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), are gaining popularity in postamputation pain treatment with promising results. However, these two methods have not been directly compared in a randomised controlled trial (RCT). Here, we present a study protocol for an international, double-blind, RCT to assess the effectiveness of TMR, RPNI, and a non-reconstructive procedure called neuroma transposition (active control) in alleviating RLP, neuroma pain, and PLP.

Methods: One hundred ten upper and lower limb amputees suffering from RLP will be recruited and assigned randomly to one of the surgical interventions (TMR, RPNI, or neuroma transposition) in an equal allocation ratio. Complete evaluations will be performed during a baseline period prior to the surgical intervention, and follow-ups will be conducted in short term (1, 3, 6, and 12 months post-surgery) and in long term (2 and 4 years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participant is unsatisfied with the outcome of the treatment at that time, further treatment including one of the other procedures will be discussed in consultation with the clinical investigator at that site.

Discussion: A double-blind RCT is necessary for the establishment of evidence-based procedures, hence the motivation for this work. In addition, studies on pain are challenging due to the subjectivity of the experience and the lack of objective evaluation methods. Here, we mitigate this problem by including different pain evaluation methods known to have clinical relevance. We plan to analyse the primary variable, mean change in NRS (0-10) between baseline and the 12-month follow-up, using the intention-to-treat (ITT) approach to minimise bias and keep the advantage of randomisation. The secondary outcomes will be analysed on both ITT and per-protocol (PP). An adherence protocol (PP population) analysis will be used for estimating a more realistic effect of treatment.

Trial registration: ClincialTrials.gov NCT05009394.

Keywords: Neuroma pain; Phantom limb pain; Randomised controlled trial; Regenerative peripheral nerve interfaces; Residual limb pain; Stump pain; Targeted muscle reinnervation.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2023. The Author(s).

Figures

Fig. 1

Illustration of the three different pain types: neuroma pain, residual limb pain, and phantom limb pain. Note that neuroma and residual limb pain can be felt anywhere in the residual limb

Fig. 2

Study flowchart of the double-blind, randomised controlled trial. One hundred ten lower and upper amputees are recruited and randomly assigned to one of the surgical treatments for postamputation pain in an equal allocation ratio. The follow-up is short term (1 to 12 months post-surgery) as well as long term (2 and 4 years post-surgery). The study will be unblinded 12 months post-surgery, where treatment outcomes will be discussed in consultation with the clinical investigator at the site

Fig. 3

Schematic illustration of the three surgical approaches included in the trial: targeted muscle reinnervation (TMR), regenerative peripheral nerve interface (RPNI), and standard treatment (neuroma transposition)