Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2016

Open Access 01-12-2016 | Study protocol

A randomised, patient-assessor blinded, sham-controlled trial of external non-invasive peripheral nerve stimulation for chronic neuropathic pain following peripheral nerve injury (EN-PENS trial): study protocol for a randomised controlled trial

Authors: Selina Johnson, Roberta Richey, Emily Holmes, Dyfrig Hughes, Andreas Goebel

Published in: Trials | Issue 1/2016

Login to get access

Abstract

Background

Eight percent of people in the UK are estimated to have persistent (chronic) neuropathic pain, and for many there is no effective treatment. Medications are the most common first-line treatment but often have limited benefit or adverse events. Surgical treatments, such as spinal cord stimulation, are then often considered. External non-invasive peripheral nerve stimulation (EN-PENS) is a form of electrical stimulation that involves placing a pen-shaped electrode onto the skin, which can be easily self-administered by patients. Observational studies suggest that EN-PENS may relieve pain for people with localised neuropathic pain; however, there is currently no evidence from controlled trials to confirm the efficacy and confidently determine the effect size for patients with longstanding neuropathic pain.

Methods

EN-PENS is a single-site, blinded, randomised controlled parallel-group superiority add-on trial with a 1:1 allocation ratio, designed to evaluate the efficacy of treatment versus control treatment in 76 patients with longstanding neuropathic pain following peripheral nerve injury. Patients with moderate to -severe neuropathic pain following peripheral nerve injury will be randomised to receive either the active or control treatment, followed by an optional treatment extension or treatment switch to the alternative treatment arm. The primary outcome is average 24-h pain intensity recorded on an 11-point (0–10) numerical rating scale, averaged over the last 7 days of treatment.

Discussion

Study results will be used to inform potential treatment efficacy and cost-effectiveness of EN-PENS for this population group.

Trial registration

ISRCTN53432663. Registered on 7 July 2016.
Literature
1.
Treede R-D, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630–5.CrossRefPubMed
2.
Andrew R, Derry S, Taylor RS, Straube S, Phillips CJ. The costs and consequences of adequately managed chronic non‐cancer pain and chronic neuropathic pain. Pain Pract. 2014;14:79–94.CrossRefPubMed
3.
Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006;7:281–9.CrossRefPubMed
4.
Jensen MP, Chodroff MJ, Dworkin RH. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology. 2007;68:1178–82.CrossRefPubMed
5.
Beniczky S, Tajti J, Varga ET, Vecsei L. Evidence-based pharmacological treatment of neuropathic pain syndromes. J Neural Transm. 2005;112:735–49.CrossRefPubMed
6.
7.
O’Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med. 2009;122:S22–32.CrossRefPubMed
8.
Cruccu G, Aziz TZ, Garcia‐Larrea L, Hansson P, Jensen TS, Lefaucheur J, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol. 2007;14:952–70.CrossRefPubMed
9.
Hamza MA, White PF, Craig WF, Ghoname ES, Ahmed HE, Proctor TJ, et al. Percutaneous electrical nerve stimulation: a novel analgesic therapy for diabetic neuropathic pain. Diabetes Care. 2000;23:365–70.CrossRefPubMed
10.
Slotty PJ, Vesper J, Pohlmeier K, Wille C. Predicting outcome in peripheral nerve stimulation for chronic neuropathic pain. Neuromodulation. 2013;2013:483–9. doi:10.​1111/​ner.​12091.CrossRef
11.
12.
Rottmann S, Jung K, Ellrich J. Electrical low-frequency stimulation induces homotopic long-term depression of nociception and pain from hand in man. Clin Neurophysiol. 2008;119:1895–904.CrossRefPubMed
13.
Klein T, Magerl W, Hopf H-C, Sandkühler J, Treede R-D. Perceptual correlates of nociceptive long-term potentiation and long-term depression in humans. J Neurosci. 2004;24:964–71.CrossRefPubMed
14.
15.
Mücke M, Cuhls H, Radbruch L, Weigl T, Rolke R. Evidence of heterosynaptic LTD in the human nociceptive system: superficial skin neuromodulation using a matrix electrode reduces deep pain sensitivity. PLoS One. 2014;9:e107718.CrossRefPubMedPubMedCentral
16.
Ellrich J, Schorr A. Low-frequency stimulation of trigeminal afferents induces long-term depression of human sensory processing. Brain Res. 2004;996:255–8.CrossRefPubMed
17.
Carroll D, Moore RA, McQuay HJ, Fairman F, Tramer M, Leijon G. Transcutaneous electrical nerve stimulation (TENS) for chronic pain. Cochrane Database Syst Rev. 2001;3:CD003222.
18.
19.
20.
Johnson S, Goebel A. Long-term treatment of chronic neuropathic pain using external noninvasive external peripheral nerve stimulation in five patients. Neuromodulation. 2015. doi:10.​1111/​ner.​12365.
21.
Kothari S, Goroszeniuk T. 602 External neuromodulation (EN) as a diagnostic test and therapeutic procedure. Eur J Pain. 2006;10:S158.CrossRef
22.
Kothari S, Goroszeniuk T, Reddy R, Khan R. Neuromodulation (NM) of the distal sciatic/popliteal nerve for neuropathic pain of leg, foot and ankle: 666. Reg Anesth Pain Med. 2008;33:e211.
23.
Goroszeniuk T, Kothari S. Targeted external area stimulation: 240. Reg Anesth Pain Med. 2004;29:98.CrossRef
24.
Athmaja Azzopardi J, Goroseniuk T, Kothari ST. External neuromodulation for “little big sting” CRPS following post phlebotomy nerve injury. Reg Anesth Pain Med. 2009;34:1–193.
25.
26.
Campbell WW. Evaluation and management of peripheral nerve injury. Clin Neurophysiol. 2008;119:1951–65.CrossRefPubMed
27.
Hassenbusch SJS, Stanton-Hicks M, Schoppa D, Walsh JJG, Covington ECE. Long-term results of peripheral nerve stimulation for reflex sympathetic dystrophy. J Neurosurg. 1996;84:415–23.CrossRefPubMed
28.
Rottmann S, Jung K, Ellrich J. Electrical low‐frequency stimulation induces long‐term depression of sensory and affective components of pain in healthy man. Eur J Pain. 2010;14:359–65.CrossRefPubMed
29.
Raphael JH, Raheem TA, Southall JL, Bennett A, Ashford RL, Williams S. Randomized double‐blind sham‐controlled crossover study of short‐term effect of percutaneous electrical nerve stimulation in neuropathic pain. Pain Med. 2011;12:1515–22.CrossRefPubMed
30.
Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113:9–19.CrossRefPubMed
31.
Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994;23:129–38.PubMed
32.
EuroQol Group. EuroQol—a new facility for the measurement of health-related quality of life. Health Policy (New York). 1990;16:199–208.
33.
Curtis L, Netten A. Unit costs of health and social care. Kent: University of Kent; 2005.
34.
Beecham J, Knapp M. Costing psychiatric interventions. In: Thornicroft G, editor. Measuring mental health needs. 2nd ed. London: Gaskell; 2001. p. 200–24.
35.
Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 1983;67:361–70.CrossRefPubMed
36.
Anderson KO, Dowds BN, Pelletz RE, Edwards WT, Peeters-Asdourian C. Development and initial validation of a scale to measure self-efficacy beliefs in patients with chronic pain. Pain. 1995;63:77–83.CrossRefPubMed
37.
Love‐Jones SJ, Besson M, Steeds CE, Brook P, Chizh BA, Pickering AE. Homotopic stimulation can reduce the area of allodynia in patients with neuropathic pain. Eur J Pain. 2009;13:942–8.CrossRefPubMed
38.
Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, et al. Development and validation of the Neuropathic Pain Symptom Inventory. Pain. 2004;108:248–57.CrossRefPubMed
39.
Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective outcome measures. J Manipulative Physiol Ther. 2004;27:26–35.CrossRefPubMed
40.
Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med. 2001;134:663–94.CrossRefPubMed
41.
42.
Schafer JL. Analysis of incomplete multivariate data. Boca Raton: CRC Press; 1997.CrossRef
43.
Royston P. Multiple imputation of missing values: update of ice. Stata J. 2005;5:527.
44.
Bender R, Grouven U. Ordinal logistic regression in medical research. J R Coll Physicians Lond. 1997;31:546–51.PubMed
45.
Keselman HJ, Huberty CJ, Lix LM, Olejnik S, Cribbie RA, Donahue B, et al. Statistical practices of educational researchers: an analysis of their ANOVA, MANOVA, and ANCOVA analyses. Rev Educ Res. 1998;68:350–86.CrossRef
46.
Rao JNK, Scott AJ. The analysis of categorical data from complex sample surveys: chi-squared tests for goodness of fit and independence in two-way tables. J Am Stat Assoc. 1981;76:221–30.CrossRef
47.
Ridyard CH, Hughes DA. Methods for the collection of resource use data within clinical trials: a systematic review of studies funded by the UK health technology assessment program. Value Heal. 2010;13:867–72.CrossRef
48.
Joint Formulary Committee, Royal Pharmaceutical Society of Great Britain. British national formulary (BNF) 64. London: Pharmaceutical Press; 2012.
49.
Department of Health. Attributing the costs of health and social care Research & Development (AcoRD). London: Department of Health; 2012. p. 10.
50.
Glick HA, Doshi JA, Sonnad SS. In Polsky D, editor. Economic evaluation in clinical trials. Oxford: Oxford University Press; 2014.
Metadata
Title
A randomised, patient-assessor blinded, sham-controlled trial of external non-invasive peripheral nerve stimulation for chronic neuropathic pain following peripheral nerve injury (EN-PENS trial): study protocol for a randomised controlled trial
Authors
Selina Johnson
Roberta Richey
Emily Holmes
Dyfrig Hughes
Andreas Goebel
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1709-2

Other articles of this Issue 1/2016

Trials 1/2016 Go to the issue

Research

Vitamin D intervention in preschoolers with viral-induced asthma (DIVA): a pilot randomised controlled trial

Study protocol

Spectacle wearing in children randomised to ready-made or custom spectacles, and potential cost savings to programmes: study protocol for a randomised controlled trial

Study protocol

START NOW - a comprehensive skills training programme for female adolescents with oppositional defiant and conduct disorders: study protocol for a cluster-randomised controlled trial

Study protocol

Gait training assisted by multi-channel functional electrical stimulation early after stroke: study protocol for a randomized controlled trial

Study protocol

Polypharmacy in chronic diseases–Reduction of Inappropriate Medication and Adverse drug events in older populations by electronic Decision Support (PRIMA-eDS): study protocol for a randomized controlled trial

Study protocol

The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial