A Trial of Lidocaine Patch for Lower Limb Amputation Pain

A Randomized Controlled Trial of Lidocaine Patch for Lower Limb Amputation Pain

Phantom limb pain (PLP) and scar hyperalgesia (SH) are frequent problems after amputation; in particular most persons who undergo limb amputation will experience phantom pain. The neuropathic nature of PLP suggests the involvement of both peripheral and central neurological mechanisms, including neuroplastic changes in the central nervous system. PLP as other central nervous system-related pain syndromes remains a challenge for treatment. Scar hyperalgesia involves peripheral mechanisms and results frim the production of substances liberated by damaged skin cells. These inflammatory substances lower the pain threshold by altering the chemical environment of skin nerve endings. Scan hyperalgesia is associated with secondary mechanical hyperalgesia in the skin area around the scar.

The lidocaine patch 5% is a topical analgesic acting by blocking sodium channels of peripheral nerve endings and by inhibiting ectopic discharges in sensitized and hyperactive cutaneous nociceptors. The patch is noninvasive, with minimal systemic absorption resulting in a reduced risk of drug-drug interaction. In addition, a central analgesic effect of lidocaine has been suggested. The lidocaine patch 5% is currently licensed for the treatment of symptomatic postherpetic neuralgia. It also has been successfully used in patients with other neuropathic pain states, such as entrapment neuropathies, painful idiopathic distal sensory polyneuropathies and postoperative/post traumatic neuropathic chronic cutaneous pain. The lidocaine patch has not been studied for the management and prevention of phantom limb pain.

The aim of the present research is to investigate if a lidocaine patch 5% is effective for reducing PLP and primary/secondary scar hyperalgesia. The hypothesis is that persistent peripheral nociceptive input from the stump after surgery may drive maladaptive cortical reorganization leading to chronic central pain and thus promote chronic phantom limb pain. Treating scar hyperalgesia on the stump with topical lidocaine may reduce the activity of peripheral nociceptive afferents and thus decrease the likelihood of developing persistent phantom limb pain.

This study is designed as a randomized controlled multicentric double blind trial, in which the effectiveness of applying a 5% lidocaine patch for 6 weeks will be compared with a sham.

Study Overview

• Status: Withdrawn
• Conditions: Phantom Limb Pain (PLP); Primary/Secondary Scar Hyperalgesia
• Intervention / Treatment: Drug: Lidocaine; Other: Sham

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • CHU Brugmann - Queen Astrid
  • Brussels, Belgium
    • Erasme -CTR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All above or below knee amputations , two months or more after surgery, after complete wound healing (no clips, no stitches, no seepage)

Exclusion Criteria:

• History of central nervous system disease
• History of major psychiatric disease (MMS<23/30, HADS>8/21)
• Pregnancy
• Known hypersensitivity to local anesthetics (lidocaine, bupivacaine, etidocaine, mepivacaine, prilocaine)
• skin irritation on the stump

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lidocaine; During a period of six weeks, a lidocaine patch will be applied around the wound (cut in two parts, 1cm above and below the wound, without direct contact with the scar) for a total of twelve hours per day, during night time.	Drug: Lidocaine
Sham Comparator: Sham; During a period of six weeks, a visually identical patch (sham) will be applied around the wound (cut in two parts, 1cm above and below the wound, without direct contact with the scar) for a total of twelve hours per day, during night time.	Other: Sham

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported overall daily pain intensity	The overall daily pain intensity (stump, scar and phantom pain combined) will be rated on a 0 to 100 visual analogue scale with anchors of 0 (no pain) to 100 (worst pain ever experienced).	Daily, starting seven days before patch placement (baseline) till six weeks after patch placement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropathic Pain (DN4)	Screening for neuropathic pain, by using the DN4 questionnaire	at baseline - 7 days before patch placement
Neuropathic pain	Rated with the Neuropathic Pain Symptom Inventory	at baseline - 7 days before patch placement
Neuropathic pain	Rated with the Neuropathic Pain Symptom Inventory	One day after patch placement
Neuropathic pain	Rated with the Neuropathic Pain Symptom Inventory	6 weeks after patch placement
Neuropathic pain	Rated with the Neuropathic Pain Symptom Inventory	6 months after patch placement
Pain (McGill)	Rated by the Short-Form McGill Pain Questionnaire, sensitive to the effects of pain treatment.	at baseline - 7 days before patch placement
Pain (McGill)	Rated by the Short-Form McGill Pain Questionnaire, sensitive to the effects of pain treatment.	One day after patch placement
Pain (McGill)	Rated by the Short-Form McGill Pain Questionnaire, sensitive to the effects of pain treatment.	6 weeks after patch placement
Quality of life	Rated by the SF36 questionnaire	at baseline -7 days before patch placement
Quality of life	Will be rated by the SF36 questionnaire	six weeks after patch placement
Quality of life	Will be rated by the SF36 questionnaire	six months after patch placement
Sleep quality	will be assessed with the Pittsburgh Sleep Quality index	baseline -7 days before patch placement
Sleep quality	will be assessed with the Pittsburgh Sleep Quality index	6 weeks after patch placement
Sleep quality	will be assessed with the Pittsburgh Sleep Quality index	6 months after patch placement
Delay of dress of provisory prosthesis	Number of days between surgery and delivery of temporary prosthesis	From the day of the surgery till the day of the delivery of temporary prosthesis, for a maximum of 6 months
Delay of dress of provisory prosthesis	Number of days between inclusion in the research protocol and delivery of temporary prosthesis	From the day of patient inclusion in the research protocol till the day of the delivery of temporary prosthesis, for a maximum of 6 months
Cumulative analgesic consumption (morphine equivalents)	Rated by the cumulative analgesic consumption score (CACS)	baseline -7 days before patch placement
Cumulative analgesic consumption (morphine equivalents)	Rated by the cumulative analgesic consumption score (CACS)	1 day after patch placement
Cumulative analgesic consumption (morphine equivalents)	Rated by the cumulative analgesic consumption score (CACS)	6 weeks after patch placement
Phantom Limb Pain occurence	occurence of phantom limb pain	6 months after patch placement

Collaborators and Investigators

• Sponsor: Brugmann University Hospital
• Investigators: Principal Investigator: Samar Hatem, MD, CHU Brugmann; Principal Investigator: Simone Brienza, MD, CHU Brugmann; Principal Investigator: Valérie Gangji, MD, Erasme

Publications and helpful links

General Publications

• Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.
• Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lanteri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain. 2005 Mar;114(1-2):29-36. doi: 10.1016/j.pain.2004.12.010. Epub 2005 Jan 26.
• Melzack R. The short-form McGill Pain Questionnaire. Pain. 1987 Aug;30(2):191-197. doi: 10.1016/0304-3959(87)91074-8.
• Koppert W, Ostermeier N, Sittl R, Weidner C, Schmelz M. Low-dose lidocaine reduces secondary hyperalgesia by a central mode of action. Pain. 2000 Mar;85(1-2):217-24. doi: 10.1016/s0304-3959(99)00268-7.
• Gammaitoni AR, Alvarez NA, Galer BS. Safety and tolerability of the lidocaine patch 5%, a targeted peripheral analgesic: a review of the literature. J Clin Pharmacol. 2003 Feb;43(2):111-7. doi: 10.1177/0091270002239817.
• Robinson LR, Czerniecki JM, Ehde DM, Edwards WT, Judish DA, Goldberg ML, Campbell KM, Smith DG, Jensen MP. Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study. Arch Phys Med Rehabil. 2004 Jan;85(1):1-6. doi: 10.1016/s0003-9993(03)00476-3.
• HARDY JD, WOLFF HG, GOODELL H. Experimental evidence on the nature of cutaneous hyperalgesia. J Clin Invest. 1950 Jan;29(1):115-40. doi: 10.1172/JCI102227. No abstract available.
• Nalamachu S, Crockett RS, Gammaitoni AR, Gould EM. A comparison of the lidocaine patch 5% vs naproxen 500 mg twice daily for the relief of pain associated with carpal tunnel syndrome: a 6-week, randomized, parallel-group study. MedGenMed. 2006 Aug 9;8(3):33.
• Herrmann DN, Barbano RL, Hart-Gouleau S, Pennella-Vaughan J, Dworkin RH. An open-label study of the lidocaine patch 5% in painful idiopathic sensory polyneuropathy. Pain Med. 2005 Sep-Oct;6(5):379-84. doi: 10.1111/j.1526-4637.2005.00058.x.
• Hans G, Joukes E, Verhulst J, Vercauteren M. Management of neuropathic pain after surgical and non-surgical trauma with lidocaine 5% patches: study of 40 consecutive cases. Curr Med Res Opin. 2009 Nov;25(11):2737-43. doi: 10.1185/03007990903282297.
• Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, Rostaing S, Lanteri-Minet M, Collin E, Grisart J, Boureau F. Development and validation of the Neuropathic Pain Symptom Inventory. Pain. 2004 Apr;108(3):248-257. doi: 10.1016/j.pain.2003.12.024.

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2016
• Primary Completion (Actual): June 13, 2017
• Study Completion (Actual): June 13, 2017

Study Registration Dates

• First Submitted: February 26, 2016
• First Submitted That Met QC Criteria: March 1, 2016
• First Posted (Estimate): March 2, 2016

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: January 18, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: lidocaine; phantom limb pain (PLP); Primary/secondary scar hyperalgesia
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Neurobehavioral Manifestations; Sensation Disorders; Perceptual Disorders; Somatosensory Disorders; Pain, Postoperative; Phantom Limb; Hyperalgesia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: CHUB-patch lidocaine

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No