化学療法誘発性末梢神経障害におけるオゾン療法: RCT (O3NPIQ) (O3NPIQ)
化学療法誘発性末梢神経障害に続発する疼痛患者におけるオゾン療法の有効性と費用対効果。無作為化三重盲検臨床試験 (O3NPIQ)
The main objective of this clinical trial is to evaluate the effectiveness and cost-effectiveness of adding ozone therapy to the clinical management of patients with pain secondary to chemotherapy-induced peripheral neuropathy
調査の概要
詳細な説明
Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a decrease and/or interruption of the chemotherapy treatment-limiting its effectiveness. The therapeutic measures for the CIPN are very limited in their number and efficacy.
Main Objectives: 1) To evaluate the clinical effect on the health-related quality of life (HRQOL) of adding ozone to the usual patient´s treatment with persistent pain because of CIPN. 2) Estimate the additional costs and evaluate the cost-effectiveness ratio.
Secondary Objectives: To evaluate the evolution of 3) oxidative stress and chronic inflammation through biochemical measurements; 4) anxiety and depression of patients; 5) the diagnostic and predictive value of hyperspectral imaging in the assessment of pain; 6) the acceptability of patients to a shared decision-making (SDM) tool.
METHODOLOGY: Randomized controlled trial (RCT) phase II-III, randomized, triple-blind; 42 patients with any kind of cancer treated with any kind of chemotherapy, with CIPN of grade > = 2 for > = 3 months.
TREATMENT: All patients will receive: usual treatment + 40 rectal insufflation sessions of O3/O2 in 16 weeks:
- Ozone-Arm (n = 21): concentration of O3/O2 increasing from 10 to 30 μg/ml.
- Control-placebo- Arm (n = 21): concentration of O3/O2 = 0 μg/ml.
Main Variables: At the end of treatment with O3/O2 the following variables will be analyzed: 1) "average pain" secondary to CIPN following the Brief Pain Inventory-Short Form (BPI-SF); 2) health-related quality of life (HRQOL) and utilities using EQ-5D-5L and SF-36 quality of life questionnaires; 3) Direct costs.
Secondary Variables: 3) biochemical parameters of oxidative stress and inflammation; 4) Hamilton scale for anxiety and depression; 5) hyperspectral images; 6) acceptability of patients to a shared decision-making (SDM) tool.
Assessments at weeks: 0 (baseline), 16 (end of O3/O2 insufflations, objective), and 28 (end of follow-up, control).
Length of treatment: 16 weeks.
Follow-up: 12 weeks after finishing O3/O2 insufflation.
Planned length of the clinical trial: 36 months.
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Bernardino Clavo, MD, PhD
- 電話番号：(34)928449278
- メール：bernardinoclavo@gmail.com
研究連絡先のバックアップ
- 名前：Delvys Rodríguez-Abreu, MD
- 電話番号：(34)928441779
- メール：drodabr@gobiernodecanarias.org
研究場所
-
-
Las Palmas
-
Las Palmas de Gran Canaria、Las Palmas、スペイン、35016
- 募集
- Complejo Hospitalario Materno Insular
-
コンタクト：
- Delvys Rodríguez-Abreu, MD
- メール：delvysra@yahoo.com
-
Las Palmas de Gran Canaria、Las Palmas、スペイン、35019
- 募集
- Hospital Universitario de Gran Canaria Dr. Negrín
-
コンタクト：
- Bernardino Clavo, MD, PhD
- メール：bernardinoclavo@gmail.com
-
副調査官：
- Saray Galván, MD
-
副調査官：
- Francisco Rodríguez-Esparragón, BSc, PhD
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- 1. Adults > = 18 years old.
- 2. Any kind of cancer in any stage, treated with any kind of chemotherapy, and life expectancy > = 6 months.
- 3. Clinical diagnosis of painful chemotherapy-induced peripheral neuropathy, toxicity Grade 2 or higher according to the Common Toxicity Criteria for Adverse Events (CTCAE) from the National Cancer Institute of EEUU, v.5.0, for > = 3 months and without the inclusion of new treatments for pain and/or neuropathy for > = 1 month.
- 4. "Average pain" > = 3/10 according to the Brief Pain Inventory-Short Form (BPI-SF) > = 3 months beyond chemotherapy completion.
- 5. Pregnant women cannot participate in the clinical trial.
- 6. Before enrollment, women of childbearing potential should obtain a negative result in the serum or urine pregnancy test at the screening visit and accept the use of appropriate contraceptive methods at least from the 14 days prior to the first ozone therapy session up to 14 days after the last one.
- 7. Patients who have signed and dated the study 's specific informed consent
Exclusion Criteria:
- 1. Age < 18 years old.
- 2. Pregnancy at the time of enrollment.
- 3. Women with childbearing potential who are unwilling to perform a pregnancy test and/or employ adequate contraception from the 14 days prior to the first ozone therapy session up to 14 days after the last one.
- 4. Clinical suspicion that peripheral neuropathy (compressive or diabetic neuropathy) in the same area prior to receiving neurotoxic chemotherapy.
- 5. Psychiatric illness or social situations that would limit compliance with study requirements.
- 6. Those who are unable to fill in the scales used to measure quality of life variables
- 7. Specific liver enzymes [Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) > 5 times the upper limit of normal
- 8. Increased creatinine > 3 times the upper limit of normal.
- 9. Hemodynamically or clinically unstable patients or uncontrolled severe illness.
- 10. Uncontrolled cancer disease.
- 11. Leptomeningeal carcinomatosis.
- 12. Life expectancy < 6 months
- 13. Contraindication or disability for rectal ozone administration or to attend scheduled treatments.
- 14. Known allergy to ozone.
- 15.Patients who do not meet all the inclusion criteria.
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：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Ozone Group
Drug: Ozone Ozone Group: Usual treatment + Ozone therapy (O3/O2) by rectal insufflation. O3/O2 concentration progressively increased from 10 to 30 μg/ml; 40 sessions in 16 weeks. Other Names: O3 |
Ozone Group: Standard treatment + Ozone therapy (O3/O2) by rectal insufflation. O3/O2 concentration progressively increased from 10 to 30 μg/ml; 40 sessions in 16 weeks.
他の名前：
|
|
プラセボコンパレーター：Control Group
Drug: Oxygen Control Group: Standard treatment + Oxygen (O2) by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks. Other Names: O2 |
Control Group: Standard treatment + Oxygen (O2) by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks.
他の名前：
|
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 |
|---|---|---|
|
Change from Baseline in "Average pain" according to the Brief Pain Inventory-Short Form (BPI-SF) (at the end of ozone therapy)
時間枠：16 weeks
|
Self-reported evaluation of 15 items to assess the severity of pain on daily functions in seven interference areas. From the 15 items, 11 items are scored from 0 ("No pain" or "Does not no interfere") to 10 ("Pain as bad as you can imagine" or "Completely interferes"). |
16 weeks
|
|
Direct Hospital Cost (at the end of ozone therapy)
時間枠：16 weeks
|
The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 16 weeks of ozone therapy (in euros). |
16 weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at the end of ozone therapy)
時間枠：16 weeks
|
Self-reported evaluation of: a) 5 physical and emotional items scored in five levels, from 1 (best: I have no problem) to 5 (worst: I have extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analogue scale (0 = worst health patient can imagine, 100 = best health patient can imagine) |
16 weeks
|
|
Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36v2) questionnaire (at the end of ozone therapy)
時間枠：16 weeks
|
Self-reported evaluation of 36 items (0 = worst, 100 = best). Final accumulated total range from 0 (worst) to 100 (best) |
16 weeks
|
|
Change from Baseline in Biochemical parameters of oxidative stress (at the end of ozone therapy)
時間枠：16 weeks
|
Serum levels of superoxide dismutase, glutathione, glutathione peroxidase and free radicals |
16 weeks
|
|
Change from Baseline in Biochemical parameters of inflammation (at the end of ozone therapy)
時間枠：16 weeks
|
Serum levels of pro-inflammatory interleukins and TNFalpha |
16 weeks
|
|
Change from Baseline in Hyperspectral image of painful area (at the end of ozone therapy)
時間枠：16 weeks
|
Assessment of the percentage of reflectance for each wavelength |
16 weeks
|
|
Change from Baseline in Levels of anxiety and depression according to the Hamilton scale (at the end of ozone therapy)
時間枠：16 weeks
|
Clinician-administered depression assessment scale with 17 items pertaining to symptoms of depression experienced over the past week. Each item is scored from 0 (better, no alteration) to 2 (worse level of alteration) for items with three options, or from or from 0 (better, no alteration) to 4 (worse level of alteration) for items with five options. Overall score is from 0 (better, no anxiety/depression) to 52 (worse, very severe anxiety/depression). |
16 weeks
|
|
Change from Baseline in Nerve conduction studies in the painful area (at the end of ozone therapy)
時間枠：16 weeks
|
Assessment of nerve conduction velocity (in m/s) |
16 weeks
|
|
Incidence of severe adverse events in accordance with the definition of the Council for International Organizations of Medical Sciences (at the end of ozone therapy)
時間枠：16 weeks
|
Number of events that are fatal, life threatening, leading to or prolonging a stay in hospital, or resulting in severe disability |
16 weeks
|
|
Change from Baseline in "Average pain" according to the Brief Pain Inventory-Short Form (BPI-SF) (at 12 weeks after the end of ozone therapy)
時間枠：28 weeks
|
Self-reported evaluation of 15 items to assess the severity of pain on daily functions in seven interference areas. From the 15 items, 11 items are scored from 0 ("No pain" or "Does not no interfere") to 10 ("Pain as bad as you can imagine" or "Completely interferes") |
28 weeks
|
|
Direct Hospital Cost (at 12 weeks after the end of ozone therapy)
時間枠：28 weeks
|
The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 16 weeks of ozone therapy (in euros) |
28 weeks
|
|
Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at 12 weeks after the end of ozone therapy)
時間枠：28 weeks
|
Self-reported evaluation of: a) 5 physical and emotional items scored in five levels, from 1 (best: I have no problem) to 5 (worst: I have extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analogue scale (0 = worst health patient can imagine, 100 = best health patient can imagine) |
28 weeks
|
|
Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36v2) questionnaire (at 12 weeks after the end of ozone therapy)
時間枠：28 weeks
|
Self-reported evaluation of 36 items (0 = worst, 100 = best). Final accumulated total range from 0 (worst) to 100 (best) |
28 weeks
|
|
Change from Baseline in Biochemical parameters of oxidative stress (at 12 weeks after the end of ozone therapy)
時間枠：28 weeks
|
Serum levels of superoxide dismutase, glutathione, glutathione peroxidase and free radicals |
28 weeks
|
|
Change from Baseline in Biochemical parameters of inflammation (at 12 weeks after the end of ozone therapy)
時間枠：28 weeks
|
Serum levels of pro-inflammatory interleukins and TNFalpha |
28 weeks
|
|
Change from Baseline in Hyperspectral image of painful area (at 12 weeks after the end of ozone therapy)
時間枠：28 weeks
|
Assessment of the percentage of reflectance for each wavelength |
28 weeks
|
|
Change from Baseline in Levels of anxiety and depression according to the Hamilton scale (at 12 weeks after the end of ozone therapy)
時間枠：28 weeks
|
Clinician-administered depression assessment scale with 17 items pertaining to symptoms of depression experienced over the past week. Each item is scored from 0 (better, no alteration) to 2 (worse level of alteration) for items with three options, or from or from 0 (better, no alteration) to 4 (worse level of alteration) for items with five options. Overall score is from 0 (better, no anxiety/depression) to 52 (worse, very severe anxiety/depression) |
28 weeks
|
|
Change from Baseline in Nerve conduction studies in the painful area (at 12 weeks after the end of ozone therapy)
時間枠：28 weeks
|
Assessment of nerve conduction velocity (in m/s) |
28 weeks
|
|
Incidence of severe adverse events in accordance with the definition of the Council for International Organizations of Medical Sciences (at 12 weeks after the end of ozone therapy)
時間枠：28 weeks
|
Number of events that are fatal, life threatening, leading to or prolonging a stay in hospital, or resulting in severe disability |
28 weeks
|
協力者と研究者
協力者
捜査官
- スタディチェア：Bernardino Clavo, MD, PhD、Dr. Negrín University Hospital, Las Palmas, Spain
- スタディディレクター：Pedro G Serrano-Aguilar, MD, PhD、Servicio de Evaluación. Servicio Canario de Salud. Spain
- 主任研究者：Delvys Rodríguez-Abreu, MD、Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas, Spain
- 主任研究者：Gustavo M Callico, Prof, PhD、Institute for Applied Microelectronics, University of Las Palmas de G. C., Spain
- 主任研究者：Francisco Rodríguez-Esparragón, BSc, PhD、Dr. Negrín University Hospital, Las Palmas, Spain
- 主任研究者：Bernardino Clavo, MD, PhD、Dr. Negrín University Hospital, Las Palmas, Spain
出版物と役立つリンク
一般刊行物
- Clavo B, Martinez-Sanchez G, Rodriguez-Esparragon F, Rodriguez-Abreu D, Galvan S, Aguiar-Bujanda D, Diaz-Garrido JA, Canas S, Torres-Mata LB, Fabelo H, Tellez T, Santana-Rodriguez N, Fernandez-Perez L, Marrero-Callico G. Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial. Int J Mol Sci. 2021 Mar 10;22(6):2802. doi: 10.3390/ijms22062802.
- Clavo B, Rodriguez-Abreu D, Galvan S, Federico M, Martinez-Sanchez G, Ramallo-Farina Y, Antonelli C, Benitez G, Rey-Baltar D, Jorge IJ, Rodriguez-Esparragon F, Serrano-Aguilar P. Long-term improvement by ozone treatment in chronic pain secondary to chemotherapy-induced peripheral neuropathy: A preliminary report. Front Physiol. 2022 Aug 30;13:935269. doi: 10.3389/fphys.2022.935269. eCollection 2022.
- Smith EM, Pang H, Cirrincione C, Fleishman S, Paskett ED, Ahles T, Bressler LR, Fadul CE, Knox C, Le-Lindqwister N, Gilman PB, Shapiro CL; Alliance for Clinical Trials in Oncology. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA. 2013 Apr 3;309(13):1359-67. doi: 10.1001/jama.2013.2813.
- Durand JP, Deplanque G, Montheil V, Gornet JM, Scotte F, Mir O, Cessot A, Coriat R, Raymond E, Mitry E, Herait P, Yataghene Y, Goldwasser F. Efficacy of venlafaxine for the prevention and relief of oxaliplatin-induced acute neurotoxicity: results of EFFOX, a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2012 Jan;23(1):200-205. doi: 10.1093/annonc/mdr045. Epub 2011 Mar 22.
- Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, Chauhan C, Gavin P, Lavino A, Lustberg MB, Paice J, Schneider B, Smith ML, Smith T, Terstriep S, Wagner-Johnston N, Bak K, Loprinzi CL; American Society of Clinical Oncology. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014 Jun 20;32(18):1941-67. doi: 10.1200/JCO.2013.54.0914. Epub 2014 Apr 14.
- Bocci V, Borrelli E, Travagli V, Zanardi I. The ozone paradox: ozone is a strong oxidant as well as a medical drug. Med Res Rev. 2009 Jul;29(4):646-82. doi: 10.1002/med.20150.
- Bocci VA, Zanardi I, Travagli V. Ozone acting on human blood yields a hormetic dose-response relationship. J Transl Med. 2011 May 17;9:66. doi: 10.1186/1479-5876-9-66.
- Bocci V, Valacchi G. Nrf2 activation as target to implement therapeutic treatments. Front Chem. 2015 Feb 2;3:4. doi: 10.3389/fchem.2015.00004. eCollection 2015.
- Clavo B, Ceballos D, Gutierrez D, Rovira G, Suarez G, Lopez L, Pinar B, Cabezon A, Morales V, Oliva E, Fiuza D, Santana-Rodriguez N. Long-term control of refractory hemorrhagic radiation proctitis with ozone therapy. J Pain Symptom Manage. 2013 Jul;46(1):106-12. doi: 10.1016/j.jpainsymman.2012.06.017. Epub 2012 Oct 26.
- Clavo B, Rodriguez-Esparragon F, Rodriguez-Abreu D, Martinez-Sanchez G, Llontop P, Aguiar-Bujanda D, Fernandez-Perez L, Santana-Rodriguez N. Modulation of Oxidative Stress by Ozone Therapy in the Prevention and Treatment of Chemotherapy-Induced Toxicity: Review and Prospects. Antioxidants (Basel). 2019 Nov 26;8(12):588. doi: 10.3390/antiox8120588.
- Clavo B, Navarro M, Federico M, Borrelli E, Jorge IJ, Ribeiro I, Rodriguez-Melcon JI, Carames MA, Santana-Rodriguez N, Rodriguez-Esparragon F. Ozone Therapy in Refractory Pelvic Pain Syndromes Secondary to Cancer Treatment: A New Approach Warranting Exploration. J Palliat Med. 2021 Jan;24(1):97-102. doi: 10.1089/jpm.2019.0597. Epub 2020 May 5.
- Clavo B, Navarro M, Federico M, Borrelli E, Jorge IJ, Ribeiro I, Rodriguez-Melcon JI, Carames MA, Santana-Rodriguez N, Rodriguez-Esparragon F. Long-Term Results with Adjuvant Ozone Therapy in the Management of Chronic Pelvic Pain Secondary to Cancer Treatment. Pain Med. 2021 Sep 8;22(9):2138-2141. doi: 10.1093/pm/pnaa459. No abstract available.
- Albers JW, Chaudhry V, Cavaletti G, Donehower RC. Interventions for preventing neuropathy caused by cisplatin and related compounds. Cochrane Database Syst Rev. 2014 Mar 31;2014(3):CD005228. doi: 10.1002/14651858.CD005228.pub4.
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
追加の関連 MeSH 用語
その他の研究ID番号
- 2018-156-1
- PI 19/00458 (その他の助成金/資金番号：Instituto de Salud Carlos III)
- 016/2019 (その他の助成金/資金番号：Fundación DISA)
- BF1-19-03 (その他の助成金/資金番号：Fundación Española del Dolor (FED))
- 2019 (米国 NIH グラント/契約)
- 2019-000821-37 (EudraCT番号)
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?
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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