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

July 7, 2022 updated by: Gamal Mohamed Taha Abouelmagd

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Alexandria, Egypt
        • Egypt Medical Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 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.
Drug: Normal saline
200 ml normal saline over forty minutes pre each chemotherapy session until end of the cycle.
Other Names:
  • C
Experimental: Group lidocaine infusion (L)
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
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.
Other Names:
  • L
Experimental: 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.
Drug: Duloxetine 30 MG
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
Other Names:
  • D

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Neuropathic pain characters and severity
Time Frame: every week for 12 weeks (after each chemotherapy session)
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 ).
Time Frame: Baseline (before starting chemotherapy protocol), one month ,two month and at 12 weeks ( end of chemotherapy cycle)
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 .
Time Frame: Baseline (before starting chemotherapy protocol) then 12 weeks later ( end of chemotherapy cycle)
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 .
Time Frame: Baseline (before starting chemotherapy protocol) then 12 weeks later ( end of chemotherapy cycle)
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 .
Time Frame: Baseline (before starting chemotherapy protocol) then 12 weeks later ( end of chemotherapy cycle)
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)
Time Frame: Baseline (before starting chemotherapy protocol), then every week for 12 weeks (after each chemotherapy session)
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
Time Frame: Baseline (before starting chemotherapy protocol) then 12 weeks later ( end of chemotherapy cycle)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gamal Mohamed Taha Abouelmagd

Investigators

  • Study Director: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2021

Primary Completion (Actual)

June 8, 2022

Study Completion (Actual)

July 5, 2022

Study Registration Dates

First Submitted

January 16, 2021

First Submitted That Met QC Criteria

January 28, 2021

First Posted (Actual)

February 1, 2021

Study Record Updates

Last Update Posted (Actual)

July 11, 2022

Last Update Submitted That Met QC Criteria

July 7, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1216-4-011

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All IPD collected can be shared with other researchers in other studies as described by the main investigators. Personal data will never be shared.

IPD Sharing Time Frame

Data will be available once collected and reported in study database.

IPD Sharing Access Criteria

All IPD collected can be shared with other researchers in other studies as described by the main investigators. Personal data will never be shared.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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