Patients With Taxane-induced Chronic Neuropathic Pain
Conditions
Keywords
chronic neuropathic pain, taxanes, moderate to severe pain, skin biopsy
Brief summary
The goal of this study is to compare the evolution of the density of small nerve fibers assessed with skin biopsies at the foot between two groups of patients with taxane-induced chronic neuropathic pain matched for sex and age: one group treated with applications of capsaicin 8% and a control group who received a systemic treatment. The hypothesis for the capsaicin 8% arm is that in the chronic phase, in the absence in the nervous environment of the toxic agent (in this case taxanes) causing the neuropathy and the functional modifications at the origin of pain, the new small fibers could regenerate without these pathological alterations. Our analysis will be based on the demonstration of structural abnormalities of small nerve fibers by means of skin biopsy, but also of functional abnormalities using four validated tests commonly used in this field: quantitative sensory testing (QST), laser evoked potential recordings, Sudoscan and confocal corneal microscopy.
Detailed description
The skin biopsies will be performed before the first capsaicin application and before the third application, that is to say 4 to 6 months after the first application. Patients will continue then to be followed for up to one year and another skin punch biopsy will be performed after the fifth 8% capsaicin application (i.e. 8 to 12 months after the first application). To analyze the relationships between the structural (i.e. fiber density) and functional (i.e. laser evoked potentials (PEL), QST and Sudoscan) changes in small fibers and the clinical effects of the treatment on pain intensity in the 2 groups. To verify whether the measurement of small corneal fiber density before treatment by the non-invasive technique of corneal confocal microscopy (CCM) (which is known to be correlated with lower limb small fiber density), could be predictive of the response to capsaicin 8%. An interim analysis will be requested from the ethics committee in France to analyze the data of the first 30 patients
Interventions
The hypothesis is that in the chronic phase, in the absence in the nervous environment of the toxic agent (in this case taxanes) causing the neuropathy and the functional modifications at the origin of pain, the new small fibers could regenerate without these pathological alterations (in particular the changes in the membrane excitability responsible for pain). Thus, capsaicin could, in this specific clinical context, have a "curative" effect on neuropathic pain. However, since the action of capsaicin only concerns small fibers, one cannot expect a global improvement of the neuropathy, which affects all the fibers
DRUGantidepressants (tricyclics and serotonin reuptake inhibitor SRIs), antiepiletics, lidocaine patches, and neurostimulation
These treatments are administered to patients according to the French recommendations on the management of neuropathic pain from 2020.
Sponsors
Hospital Ambroise Paré Paris
Institut Curie
Grünenthal GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients over 18 years of age with no age limit * having given their signed consent for participation in the study * affiliated with the social security system * able to be followed for the entire duration of the study * reading and understanding French * accepting the principle of the study and able to respect its conditions * presenting sensorimotor or sensory neuropathy induced by taxanes (paclitaxel or docetaxel) of the lower limbs for at least 3 months based on a complete clinical examination, the severity of which will be assessed by the NCI-CTCAE version 5 criteria (grade 2 to 4). An electromyogram (EMG) will be performed in the absence of a recent electromyogram (less than one year) to assess the function of large fibers, but its normality will not constitute an exclusion criterion (due to the possibility of chemotherapy-induced small fiber neuropathies). * presenting chronic neuropathic pain in the lower limbs for at least 3 months, with a DN4 questionnaire score ≥ 4/10 and of at least moderate intensity on an 11-point numerical scale (≥ 4/10) * whose pain is located in the lower limbs allowing the application of 8% capsaicin * without treatment or having stable analgesic treatment for at least 2 weeks before inclusion
Exclusion criteria
* litigation or compensation-seeking * metastatic cancer * Known cause of sensory neuropathy such as diabetes, systemic disease, hypothyroidism, alcohol, kidney failure, or genetic disease * Peripheral or central nervous system pathology with or without associated neuropathic pain * Uncontrolled chronic pathology such as morbid obesity, sleep apnea, uncontrolled hypertension, etc. * Psychosis, previous suicide attempt, or major depressive episode at the time of assessment * Drug or psychoactive substance abuse * Cognitive or psychological disorders incompatible with compliance with and/or understanding of the protocol * Patients participating in another biomedical research protocol * Contraindications to confocal corneal microscopy, including the wearing of long-term contact lenses or ocular procedures (eye surgery, laser for myopia, dry eye). * Pregnant or breastfeeding women * Persons under legal protection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| density of small nerve fibers | From enrollment to the end of treatment at 12 months | This clinical trial is a pathophysiology protocol. The primary objective of this study is to compare baseline at 3 and 12 months the density of small nerve fibers in the feet using a skin biopsy between two groups of patients with taxane-induced chronic neuropathic pain matched for sex and age. One group treated with two applications of capsaicin 8% and a control group who received a systemic treatment. All treatments used in the clinical trial are recommended by international experts for treating neurpathic pain and are approved by the French Medicines Agency. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| patient reported outcomes and skin biopsy; CCM and skin biopsy; PEL and skin biopsy | From enrollment to the end of treatment at 12 months. | Correlation between intraepidermal nerve fiber density (skin biopsy) and pain (11-point numerical rating scale, Brief Pain Inventory, Neuropathic Pain Symptom Inventory, EORTC CIPN20, catastrophizing) and other domains to be studied in clinical trials on chronic pain (EQ5D quality of life, PROMIS sleep, IPAQ physical activity, Beck Depression Inventory anxiety). Correlation between intraepidermal nerve fiber density (skin biopsy) and small nerve fiber functionality (Sudoscan, laser evoked potentials). Correlation between baseline nerve fiber density assessed by confocal corneal microscopy and the efficacy of 8% capsaicin. |
Countries
France
Contacts
CONTACTDidier BOUHASSIRA, MD, PhD
CONTACTMarie PECHARD, MD
STUDY_DIRECTORDidier BOUHASSIRA, MD, PhD
Institut National de la Santé Et de la Recherche Médicale, France
Outcome results
None listed