Lidocaine Versus Duloxetine for the Prevention of Taxane-Induced Peripheral Neuropathy In Breast Cancer Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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Patients' assessment: Medical history (Previous diseases and medications) Clinical examination and laboratory investigations (according to patient' condition). Each patient will be informed with the study, its expected result and its possible side effects. The patients will be trained to use neuropathic pain scale (NPS). Additionally, DN4 questionnaire will be explained to all participants. IV line will be inserted for all participants. Vital signs including heart rate and mean arterial blood pressure will be measured. The participants will be randomly allocated into three groups as follows: Group control (C): 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): 20 adult breast cancer patients on Taxane chemo protocol will receive lidocaine IV 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): 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. 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 Nerve conduction study will be performed to detect sensory peripheral neuropathy pre and immediately after the end of chemo protocol cycle. Detection of TIPN will be measured using DN4 questionnaire before starting chemotherapy protocol and after each chemotherapy session which is expected to be one session every week for 12 weeks 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.

Official Title
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Intravenous Lidocaine Infusion Versus Oral Duloxetine For The Prevention And Treatment Of Chemotherapy Induced Peripheral Neuropathy Among Breast Cancer Patients

Conditions
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Peripheral Neuropathy, Chemotherapy-induced Peripheral Neuropathy, Breast Cancer

Intervention / Treatment
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* Drug: Lidocaine in Saline
* Drug: Duloxetine 30 MG
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: breast cancer at any stage, Taxane chemo-protocol. Exclusion Criteria: Documented history of gloves and stock neuropathy. Alcohol abuse. Abnormal renal or liver function tests. Allergy to local anesthetics. Myocardial infarction within 6 months Profound high-grade arrhythmias. Patients with neurological or psychological problems. Diabetes Mellitus. History of previous chemotherapy treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group Control (C)<br>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. | Drug: Normal saline<br>* 200 ml normal saline over forty minutes pre each chemotherapy session until end of the cycle.<br>* Other names: C;|
| Experimental: Group lidocaine infusion (L)<br>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. | Drug: Lidocaine in Saline<br>* 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.<br>* Other names: L;|
| Experimental: Group duloxetine (D)<br>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. | Drug: Duloxetine 30 MG<br>* 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<br>* Other names: D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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) | 

Secondary Outcome Measures

| Outcome Measure | 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). | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Chemotherapy, Lidocaine, Duloxetine, Taxane induced peripheral neuropathy (TIPN)