Neuropathic Pain, Osteoporotic Vertebral Fracture
Conditions
Keywords
Lidocaine 5% Plaster, Lidocaine Patch, Osteoporosis, Pain Prevention, PainDETECT, DN4
Brief summary
Osteoporotic vertebral fractures may lead to chronic pain with a neuropathic component, which is often underdiagnosed and undertreated in older adults. This proof-of-concept randomized controlled trial aims to evaluate whether early application of a 5% lidocaine plaster can prevent the development of neuropathic pain following an osteoporotic vertebral fracture. Participants will be randomized in a 2:1 ratio to receive either a daily 5% lidocaine plaster plus standard care or standard care alone for 2 months. The primary outcome is the proportion of participants who develop neuropathic pain at 2 months, assessed using the PainDETECT questionnaire.
Detailed description
Osteoporosis is associated with an increased risk of vertebral fractures that may result in persistent pain and impaired quality of life. Beyond nociceptive pain, a substantial proportion of patients develop neuropathic pain after osteoporotic vertebral fractures, which is associated with greater pain severity, sleep disturbances, and functional impairment. Current management often identifies neuropathic pain only after it has become chronic, while systemic treatments may increase the risk of adverse events in older adults. The FLYNN study is a prospective, randomized, controlled, open-label, proof-of-concept Phase 2 clinical trial designed to evaluate whether early treatment with a 5% lidocaine plaster can prevent the development of neuropathic pain following an osteoporotic vertebral fracture. Participants aged 50 years or older with a vertebral osteoporotic fracture diagnosed within the previous month and pain intensity ≥3 on a numerical rating scale will be randomized in a 2:1 ratio to receive either daily treatment with a 5% lidocaine plaster (12 hours on/12 hours off) plus standard care or standard care alone for 2 months. The primary endpoint is the occurrence of neuropathic pain 2 months after enrollment, defined by a PainDETECT score ≥19. Secondary outcomes include neuropathic pain assessed by DN4, pain intensity, treatment compliance, adverse events, concomitant medications, sleep quality (PSQI), health-related quality of life (SF-36), and psychophysical pain characterization in participants who develop neuropathic pain.
Interventions
A 5% lidocaine plaster applied once daily for 12 hours followed by 12 hours without the plaster for 2 months.
Sponsors
University Hospital, Clermont-Ferrand
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Participants will be randomized in a 2:1 ratio to receive either a 5% lidocaine plaster plus standard care or standard care alone for 2 months. Randomization will be stratified by sex using randomly sized blocks.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participant aged 50 years or older. * Diagnosis of osteoporosis established by the treating rheumatologist. * Osteoporotic vertebral fracture diagnosed within the previous month. * Pain intensity of ≥3 on a numerical rating scale at the fracture site. * Able and willing to provide written informed consent. * Affiliated with a French health insurance system.
Exclusion criteria
* Medical or surgical condition considered by the investigator to be incompatible with study participation. * Known hypersensitivity to lidocaine, any excipient of the study treatment, or other amide-type local anesthetics. * Current treatment with Class I antiarrhythmic agents (e.g., tocainide, mexiletine) or other local anesthetics. * Inflamed or damaged skin at the intended application site (e.g., active herpes zoster lesions, dermatitis, or wounds). * Pregnant or breastfeeding women. * Women of childbearing potential not using an effective contraceptive method. * Positive urine pregnancy test for women whose menopausal status cannot be confirmed. * Participation in another clinical research study. * Individuals under legal protection or deprived of liberty. * Refusal to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development of neuropathic pain at 2 months | Baseline - Day 0 and Visit 2 - Day 60 | Percentage of participants who develop neuropathic pain 2 months after enrollment, assessed using the PainDETECT questionnaire. This self-administered questionnaire evaluates pain quality, temporal pattern, and radiation to estimate the likelihood of neuropathic pain. The total score allows classification of pain as unlikely, possible, or likely neuropathic. Neuropathic pain is defined as a PainDETECT score ≥19. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain assessment using the Neuropathic Pain Questionnaire (DN4) | Baseline - Day 0 and Visit 2 - Day 60 | Neuropathic Pain (DN4): This questionnaire estimates the probability of neuropathic pain in a patient, by means of four questions divided into ten items to be ticked. The practitioner or clinical research associate in charge of the study interviews or examines the patient and fills in the questionnaire himself. Each item is marked with a "yes" or "no" answer. Each "yes" is worth a score of 1, and each "no" is worth a score of 0. The sum of the scores gives the patient's score (out of 10); if the patient's score is equal to or greater than 4/10, the test is positive. |
| Treatment compliance | Day 1 to Day 60 | Treatment compliance in the intervention group, assessed by daily documentation of 5% lidocaine plaster application (Yes/No) in the participant daily diary throughout the 2-month treatment period. |
| Adverse events | Day 1 to Day 60 | Incidence of adverse events, assessed using the participant daily diary. Participants record the occurrence of adverse events daily (Yes/No) and provide additional details when an adverse event is reported. |
| Pain evaluation | Baseline - Day 0, Day 1 to Day 60, and Visit 2 - Day 60 | Pain evaluation assessed using an 11-point Numeric Rating Scale (NRS; 0 = no pain, 10 = worst imaginable pain). Pain is recorded at baseline, daily in the participant diary throughout the treatment period, and at the end-of-study visit |
| Concomitant medications | Day 1 to Day 60 | Concomitant medication use assessed using the participant daily diary. Participants record daily whether any concomitant medication was taken (Yes/No). When applicable, the medication name and dosage are documented. |
| The 36-Item Short Form Survey (SF-36) | Baseline - Day 0 and Visit 2 - Day 60 | The quality of life of patients is assessed by the general questionnaire 36-Item Short Form Survey (SF-36) which can be administered by self or hetero-questionnaire. The SF-36 questionnaire was developed from the Medical Outcome Study, a 149-item questionnaire that was developed to assess how the American healthcare system affects the outcome of care. The SF-36 questionnaire is composed of 36 items and makes it possible to assess the physical and mental health of an individual using eleven questions relating to eight aspects of health: Physical activity, limitations due to physical state, physical pain, perceived health, vitality, life and relationship with others, limitations due to the mental state and mental health. Scores between 0 and 100 are determined. Scores tending towards 100 indicate a better quality of life. |
| The Pittsburgh Sleep Quality Index (PSQI) | Baseline - Day 0 and Visit 2 - Day 60 | The PSQI is a self-administered questionnaire with 19 items. It was developed to measure sleep quality in the month prior to the patient interview. This questionnaire includes 7 components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, hypnotic medication use and daytime dysfunction. The global score (0 to 21) is obtained by adding the sub-scores of the 7 components, each ranging from 0 to 3 points. In the absence of an answer to one or more questions, the subtotal using this question cannot be calculated and will affect the overall score. The higher the overall score, the greater the impairment in sleep quality. An overall score \>5 is an indicator of sleep disturbance. |
| Measurement of the threshold of sensitivity and pain perception induced by a thermal stimulus (hot and cold) at the Pathway - Médoc® | Visit 2 - Day 60 | The measurements will be performed using an ATS thermode applied to the dominant arm of the patients. The Pathway-Medoc system associated with the thermode allows, from a base value of 32°C, to deliver adjustable temperature peaks (in the hot or in the cold and according to a regular slope of 1°C) and controlled by fast feedback, which allows to adapt to the different sensitivity thresholds of the C and A fibers. This device will be used to evaluate: the sensitivity threshold to heat, the sensitivity threshold to cold, the pain threshold to heat and the pain threshold to cold. The determination of each threshold will be established by an average of three measurements. |
| Central sensitization tests, measurement of the Conditioned Pain Modulation (CPM) effect | Visit 2 - Day 60 | The patients are seated, the ATS thermode associated with the Pathway is applied to the dominant forearm. From the baseline value of 32°C, the Pathway delivers a "Pain 60 / Test stimulus" for 10 seconds, and the patient scores the pain on a visual numerical scale from 0 to 100. Then, the Pathway delivers a "Pain 60 / Test stimulus" for 30 seconds, and the patient scores the pain on the same scale. Fifteen minutes after the end of the two stimulations, the patient immersed the non-dominant arm for 60 seconds in a water bath at 46.5°C. Then a second identical sequence of 10 and 30 second stimulations was performed, with the scores recorded after each stimulation on the visual numerical scale from 0 to 100. The CPM effect is measured by taking the difference between the pain scores on the visual numerical scale before and after immersion. |
Countries
France
Contacts
CONTACTLise Laclautre
PRINCIPAL_INVESTIGATORMarie-Eva PICKERING
University Hospital, Clermont-Ferrand
Outcome results
None listed