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The aim of the study is to evaluate the effect of intravenous (IV) lidocaine versus oral duloxetine on the onset and severity of TIPN in patient with breast cancer as well as evaluation of Patients' quality of life and estimation the cell mediated immunity.
The current study is a single blinded randomized controlled study, assumed that lidocaine could prevent and reduce TIPN similar to duloxetine in patient with breast cancer.
Method of randomization: The allocation sequence was generated using permuted block randomization technique and the block size was variable. Allocation sequence/code was concealed from the person allocating the participants to the intervention arms using sealed opaque envelopes.
Primary outcome: Degree of neuropathic pain measured by neuropathy pain scale (NPS) among breast cancer patients on Taxane chemotherapy after the pretreatment with either lidocaine or duloxetine.
Secondary outcomes are: The incidence of TIPN using DN4 questionnaire and nerve conduction study and Patients' quality of life using The European Organization for Research and Treatment of Cancer (EORTC) QLQ-CIPN20 as well as the Change in serum level natural killer cell to estimate cell mediated immunity.
Patients' assessment:
The participants will be randomly allocated into three groups as follows:
Measurements
Demographic features of the patients
-Age (years), Weight (kg).
Neuropathic pain characters and severity
-Intensity and characters of neuropathic pain will be measured by neuropathic pain scale (0-10cm) after each chemotherapy session which is expected to be one session every week for 12 weeks
Chemotherapy induced peripheral neuropathy
Patients' quality of life -The European Organization for Research and Treatment of Cancer (EORTC) QLQ-CIPN20 questionnaire for quality of life will be taken from patient before starting chemotherapy protocol ,one month ,two month after the treatment and at the end of treatment .
Cell mediated immunity: Natural killer cell isolation and cytotoxicity assay.
-Sample of 1ml of patients' peripheral blood will be collected on EDTA for flow cytometry to enumerate for both cytotoxic lymphocytes population (NK cells, and cytotoxic lymphocytes (ctls)). CD 56 will be used as a market for NK cells while CD8 will be used as a marker for Ctls. Cytotoxic assay will be done by measuring the release of lactate dehydrogenase (LDH) from non-viable cells (Cytotoxicity Detection kit, 630117; Clontech laboratories, Mountain View, California) according to manufacturer's instructions. Then ratio of LDH released specifically from NK cells will be carried according to the result of flow cytometry . Blood Sample will be collected at the start and the end of chemo protocol cycle of breast cancer patients.
Complications
-Any complications will occur during or after the treatment with lidocaine or duloxetine will be reported and managed accordingly.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group Control (C) | Placebo Comparator | 20 adult breast cancer patients on Taxane chemo protocol will receive 200 ml normal saline over forty minutes pre each chemotherapy session until end of the cycle. |
|
| Group lidocaine infusion (L) | Experimental | 20 adult breast cancer patients on Taxane chemo protocol will receive lidocaine i.v infusion (2 mg/kg) in 200ml saline over forty minutes with a maximum upper limit of 200 mg pre each chemotherapy session until end of the cycle. If any selected patient reported neuropathic pain (DN4 > 4) during the course of chemotherapy lidocaine (2 mg/kg) re-infused after each session. If lidocaine side effects such as circumoral numbness, twitches, metal test, tachy or bradycardia recorded at any time, lidocaine infusion will be reduced to 1mg/kg, if side effects persist, the patients will be managed accordingly as well as lidocaine infusion will be stopped and patient will be excluded from the study. |
|
| Group duloxetine (D) | Experimental | 20 adult breast cancer patients on chemotherapy will take oral duloxetine tablet 30 mg once per day starting from the night pre chemotherapy session until the end of cycle. If any selected patient reported neuropathic pain (DN4 > 4) during the course of chemotherapy the duloxetine dose will be adjusted to 60 mg daily till the end of the cycle. They also will receive 200 ml normal saline over forty minutes before each chemotherapy session until end of the cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lidocaine in Saline | Drug | Lidocaine IV infusion (2 mg/kg) in 200 ml saline over forty minutes with a maximum upper limit of 200 mg pre each chemotherapy session until end of the cycle. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Neuropathic pain characters and severity | The change in intensity and characters of neuropathic pain will be measured using Neuropathy Pain Scale (NPS). It quantifies severity of neuropathic pain (0 indicates no pain, 10 indicates the most pain imaginable). | every week for 12 weeks (after each chemotherapy session) |
| Measure | Description | Time Frame |
|---|---|---|
| Quality of life assessment using the European Organization for Research and Treatment of Cancer - Quality of life questioner - Chemotherapy induced peripheral neuropathy twenty-item scale(EORTC - QLQ - CIPN20 ). | The European Organization for Research and Treatment of Cancer (EORTC - QLQ - CIPN20) will be used to elicit patients' experience of symptoms and functional limitations related to chemotherapy induced peripheral neuropathy . It consists of 20 items with scores ranging from 1 to 4 for each item . Not at All (1), A Little (2), Quite a Bit (3), and Very much(4). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sahar A El-Karadawy, MD | Medical Research Institute - MRI | Study Director |
| Magda M Abo-Ollo, MD | Medical Research Institute - MRI | Study Director |
| Wessam Z. Alamrawy, MD | Medical Research Institute - MRI | Study Director |
| Yasmine N. Elwany, MD | Medical Research Institute - MRI | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Egypt Medical Research Institute | Alexandria | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21908200 | Background | Argyriou AA, Bruna J, Marmiroli P, Cavaletti G. Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol. 2012 Apr;82(1):51-77. doi: 10.1016/j.critrevonc.2011.04.012. Epub 2011 Sep 10. | |
| 23703410 | Background | Kosharskyy B, Almonte W, Shaparin N, Pappagallo M, Smith H. Intravenous infusions in chronic pain management. Pain Physician. 2013 May-Jun;16(3):231-49. |
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All IPD collected can be shared with other researchers in other studies as described by the main investigators. Personal data will never be shared.
Data will be available once collected and reported in study database.
All IPD collected can be shared with other researchers in other studies as described by the main investigators. Personal data will never be shared.
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|
| Duloxetine 30 MG | Drug | Oral Duloxetine tablet 30 mg once per day starting from the night pre chemotherapy during the whole period of chemotherapy cycle which expected to be three month |
|
|
| Normal saline | Drug | 200 ml normal saline over forty minutes pre each chemotherapy session until end of the cycle. |
|
|
| Baseline (before starting chemotherapy protocol), one month ,two month and at 12 weeks ( end of chemotherapy cycle) |
| Detection of Chemotherapy induced peripheral neuropathy using sensory nerve conduction latency study . | Sensory nerve conduction latency study will be performed on bilateral sural and radial nerves. It test peak latency (millisecond). | Baseline (before starting chemotherapy protocol) then 12 weeks later ( end of chemotherapy cycle) |
| Detection of Chemotherapy induced peripheral neuropathy using sensory nerve conduction amplitude study . | Sensory nerve conduction amplitude study will be performed on bilateral sural and radial nerves. It test amplitude (microvolt) . | Baseline (before starting chemotherapy protocol) then 12 weeks later ( end of chemotherapy cycle) |
| Detection of Chemotherapy induced peripheral neuropathy using sensory nerve conduction velocity study . | Sensory nerve conduction velocity study will be performed on bilateral sural and radial nerves. It test nerve conduction velocity (meter/second). | Baseline (before starting chemotherapy protocol) then 12 weeks later ( end of chemotherapy cycle) |
| Incidence of Taxane induced peripheral neuropathy (TIPN) using Douleur Neuropathique 4 questionnaire (DN4) | Detection of TIPN will be measured by DN4 questionnaire .It is a clinician-administered questionnaire consisting of 10 items. Seven items related to pain quality (i.e. subjective sensory and pain descriptors) and 3 items based on the clinical examination. Scores ≥ 4/10 indicate neuropathic pain. | Baseline (before starting chemotherapy protocol), then every week for 12 weeks (after each chemotherapy session) |
| Change in serum level of natural killer cell to estimate cell mediated immunity | CD 56 will be used as a marker for NK cells while CD8 will be used as a marker for cytotoxic lymphocytes (CtLS). | Baseline (before starting chemotherapy protocol) then 12 weeks later ( end of chemotherapy cycle) |
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| 32075507 | Background | van Haren F, van den Heuvel S, Radema S, van Erp N, van den Bersselaar L, Vissers K, Steegers M. Intravenous lidocaine affects oxaliplatin pharmacokinetics in simultaneous infusion. J Oncol Pharm Pract. 2020 Dec;26(8):1850-1856. doi: 10.1177/1078155220905011. Epub 2020 Feb 19. |
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| 24494204 | Result | Areti A, Yerra VG, Naidu V, Kumar A. Oxidative stress and nerve damage: role in chemotherapy induced peripheral neuropathy. Redox Biol. 2014 Jan 18;2:289-95. doi: 10.1016/j.redox.2014.01.006. eCollection 2014. |
| 37774185 | Derived | Abouelmagd GMT, El-Karadawy SA, Abo-Ollo MM, Elwany YN, Mohamed ER, El-Amrawy WZ. Lidocaine Infusion Versus Duloxetine for Prevention and Management of Taxane-Induced Peripheral Neuropathy among Breast Cancer Patients-A Randomized Controlled Study. Pain Physician. 2023 Sep;26(5):E497-E507. |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D008012 | Lidocaine |
| D012965 | Sodium Chloride |
| D000068736 | Duloxetine Hydrochloride |
| C007792 | Fumigant 93 |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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