Chemotherapy Induced Peripheral Neuropathy by Taxanes and Capsaicin 8%.

Официальное название

Chemotherapy Induced Peripheral Neuropathy by Taxanes: Pathophysiological Evolution and Somatosensory Response Profile to Capsaicin 8%.

Обзор

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.

Подробное описание

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

Вмешательства

• Препарат Capsaicin 8% Patch
  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 cap
• Препарат antidepressants (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.

Первичные конечные точки

• density of small nerve fibers [Срок оценки: From enrollment to the end of treatment at 12 months]

Вторичные конечные точки (1)

• patient reported outcomes and skin biopsy; CCM and skin biopsy; PEL and skin biopsy [Срок оценки: From enrollment to the end of treatment at 12 months.]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• Inserm U987 — Boulogne-Billancourt

Идентификаторы

NCT: NCT07602387 · 2023-01 · 2023-A00325-40

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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