Interest of Pregabalin (Lyrica) on the Treatment of Reflex Earache in Head and Neck Cancer. (LYRORL)

Referred otalgia is one of the symptoms of oropharynx and hypopharynx cancer. It can be primary (otodynia) or secondary (referred otalgia and projected pain). The mechanism of referred otalgia involves several non adjacent nerve territories as those of head, neck or ear. Referred otalgia is a projected pain due to injury (most of the time cancer) localized far from the ear but sharing the same innervation. In this contest, the otoscopy is normal.

Four cranial nerves participate in the sensory innervation of the external ear: the trigeminal nerve (V) via the auriculo temporal nerve (V3), the facial nerve (VII) for the Ramsay-Hunt's zone with the conch, tragus, antitragus, a part of the anthelix, of the external auditory meatus and of the eardrum, the glossopharyngeal nerve (IX) via the Jacobson's nerve for the external ear canal and the C2 and C3 cervical plexus. However, there are important interindividual anatomical variations.

The relationship between referred otalgia and probable nerve damage has been described. In he oropharynx and hypopharynx, the proximity of the sensory innervation of the ear can then explain the otalgia during the cancer progression. Then referred otalgia has a neuropathic component.

In the literature, the curative treatment of referred otalgia is the cancer treatment. However, the high intensity of referred otalgia leads the patients to a large consumption of analgesics in particular of opioids. These latter are particularly adapted for pain resulting from excess of nociceptive stimulation. Pregabalin (Lyrica®) is an analogue of gamma aminobutyric acid. This molecule binds to alpha subunit 2 delta 1 calcium dependent voltage channels in the central nervous system. its effectiveness has been demonstrated for the treatment of neuropathic pain on diabetic neuropathy, post herpetic neuralgia, lesions in the bone marrow but also the postoperative pain when the molecule is administered after the surgery. The anti hyperalgesic activity of pregabalin is at a dosage of 150mg/day in two or three daily doses.

The purpose of this study was to evaluate the activity of pregabalin administered orally for three weeks after the anesthesia consultation on the intensity of the pain of referred otalgia and on its neuropathic component.

Study Overview

• Status: Terminated
• Conditions: Earache
• Intervention / Treatment: Drug: Pregabalin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lille, France
    • CHRU, Hôpital Claude HURIEZ

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:

• referred otalgia
• ENT cancer
• ASA score 1,2 or 3
• understanding protocol
• information and free and informed consent

Exclusion Criteria:

• ASA score 4 et 5
• allergy or intolerance of pregabalin
• creatinin clearance inferior of 50ml/min (Cockcroft formula)
• liver failure
• cardiac failure
• history epilepsy
• ant hyperalgesic treatment
• minor or disabled adult
• intellectual disabilities that prevent the understanding of the protocol
• uncooperative patient
• pregnant women
• patient participating in another research protocol
• lactose intolerant patient

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group	Drug: Placebo; Three doses daily with lactose
Experimental: pregabalin group	Drug: Pregabalin; 150mg daily in three doses during three weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
decreased intensity of pain in referred otalgia	diminution of the pain intensity numerical rating scale (NRS)	three weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
neuropathic pain	diminution of the Neuropathic Pain Scale Inventory (NPSI)	Three weeks
Numeric rating Scale	referred otalgia after surgery: intensity	one, three and six months
Neuropathic Pain Symptom Inventory	referred otalgia after surgery: presence	one, three and six months

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Gilles Lebuffe, MD, PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2015
• Primary Completion (Actual): December 12, 2018
• Study Completion (Actual): December 12, 2018

Study Registration Dates

• First Submitted: October 4, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (Estimate): October 5, 2016

Study Record Updates

• Last Update Posted (Actual): October 14, 2019
• Last Update Submitted That Met QC Criteria: October 10, 2019
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: neuropathic pain, ent cancer, pregabalin
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pain; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Head and Neck Neoplasms; Earache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: 2013_21; 2014-000505-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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