Chemotherapy Induced Peripheral Neuropathy by Taxanes and Capsaicin 8%. (capsaNeP)
Chemotherapy Induced Peripheral Neuropathy by Taxanes: Pathophysiological Evolution and Somatosensory Response Profile to Capsaicin 8%.
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.
調査の概要
状態
詳細な説明
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
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Didier BOUHASSIRA, MD, PhD
- 電話番号：0033149094556
- メール：didier.bouhassira@inserm.fr
研究連絡先のバックアップ
- 名前：Marie PECHARD, MD
- 電話番号：3683 0033147111515
- メール：marie.pechard@curie.fr
研究場所
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HAUTS DE SEINE
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Boulogne-Billancourt、HAUTS DE SEINE、フランス、92100
- 募集
- Inserm U987
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コンタクト：
- Didier BOUHASSIRA, MD PHD
- 電話番号：0033149094556
- メール：didier.bouhassira@inserm.fr
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コンタクト：
- MARIE PECHARD, MD
- 電話番号：0033149095946
- メール：marie.pechard@curie.fr
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ：capsaicin 8%
The minimum time between 2 applications of capsaicin is 60 days, but this could be adapted to the patients' response and therefore could be longer (up to 3 months).
Thus, 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).
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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
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アクティブコンパレータ：other treatments
Other treatments for neuropathic pain include antidepressants (tricyclics and serotonin reuptake inhibitor SRIs), antiepiletics, lidocaine patches, and neurostimulation according to the 2020 French recommendations.
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These treatments are administered to patients according to the French recommendations on the management of neuropathic pain from 2020.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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density of small nerve fibers
時間枠：From enrollment to the end of treatment at 12 months
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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. |
From enrollment to the end of treatment at 12 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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patient reported outcomes and skin biopsy; CCM and skin biopsy; PEL and skin biopsy
時間枠：From enrollment to the end of treatment at 12 months.
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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. |
From enrollment to the end of treatment at 12 months.
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協力者と研究者
捜査官
- スタディディレクター：Didier BOUHASSIRA, MD, PhD、Institut National de la Santé Et de la Recherche Médicale, France
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 2023-01
- 2023-A00325-40 (その他の識別子：2023-A00325-40)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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