Chemotherapy Induced Neuropathy in Cancer Patients (CIN)

Evaluation of Chemotherapy Induced Neuropathy in Solid Cancer Patients

The purpose of this prospective study is to perform Nerve conduction test, Vitamin D, Vitamin B12 and NADPH oxidase 4(NOX4) expression to assess severity of chemotherapy induced Peripheral neuropathy (CIPN) in solid cancer (Head and Neck, Breast, Prostate) patients who planned for at least 4 cycle of chemotherapy in different nutrient status level and gene expression.

Study Overview

• Status: Recruiting
• Conditions: Chemotherapy-induced Peripheral Neuropathy
• Intervention / Treatment: Drug: Cisplatin, Carboplatin, Paclitaxel, Docetaxel

Detailed Description

A)Screening of neuropathy in Healthy subject and Solid cancer patient before receiving chemotherapy & after 4th cycle of chemotherapy Patient who will be included in this study undergo complete neurological examination by using Total neuropathy score clinical version and Nerve conduction velocity test at baseline (0-cycle). Patients with no signs and symptoms of neuropathy will be recruited for the study. They will be followed up during the course of treatment and will undergo complete neurological examination by Total neuropathy score clinical version and nerve conduction velocity test will be done at 4th cycle to detect CIPN. Severity of CIPN will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

B)Estimation of 1,25-dihydroxyvitamin-D and Homocysteine level in all groups at baseline & 4th cycle 10,16 Approximately five millilitre of peripheral venous blood will be collected from each patient in anticoagulant (Acid-citrate-dextrose A) and centrifuge at 2500 RPM for 5 minutes. The plasma will be transferred to another tube remaining cell content will be discarded &the plasma will be stored at -20 degree Celsius.

The estimation of Concentration 1, 25-hydroxyvitamin-D and Homocysteine using CLIA.

The entire sample will be analysed following quality control analysis to eliminate error.

C) Measurement of NOX4 gene expression by RT-PCR (Real Time Polymerase Chain Reaction) analysis in all groups at baseline & 4th cycle

• To measure expression of NOX4 gene during treatment with and without neuropathy.
• Total RNA will be extracted from blood by using Himedia RNA isolation kit and then
• The cDNA will be amplified using cDNA synthesis kit (Himedia). The cDNAs will be subjected to RT-PCR analysis using Himedia mastermix with primer sets and Housekeeping gene GAPDH.

D)Total Reactive oxygen species (ROS) by conventional Catalase and D-ROMs(reactive oxygen metabolites) test in all groups at baseline & 4th cycle E)Proteomic profile by Liquid Chromatography-Mass Spectroscopy in all groups at baseline & 4th cycle.

The cellular and mitochondrial protein post translational modification increase production of ROS.

F) Evaluation of Quality of life by using EORTC-QLQ -CIPN20 Questionnaire in all groups at baseline & 4th cycle.

The patient who are undergoing chemotherapy will be asked questions from questionnaire in their local language while waiting in outpatient department of Radiation oncology department at baseline and 4 cycle.

• Study Type: Observational
• Enrollment (Estimated): 124

Contacts and Locations

Study Locations

• India
  • Dehradun, India, 248016
    • Recruiting
    • Himalayan Hospital(Cancer Research Institute), Himalayan Institute of Medical Sciences
    • Contact: Nabin Yadav, PhD Pharmacology; Phone Number: 8887604699; Email: nabinapsyadav8@gmail.com
    • Contact: Juhi Kalra, MD Pharmacology; Phone Number: 7505147054; Email: juhikalra@srhu.edu.in
    • Sub-Investigator: Vipul Nautiyal, Radiation Oncology
    • Principal Investigator: Nabin K. Yadav, Pharmacology
    • Sub-Investigator: Juhi Kalra, Pharmacology
    • Sub-Investigator: Deepak Goel, Neurology
    • Sub-Investigator: Dilip C. Dhasmana, Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with Stage I-IV Solid Cancer who will receive Cisplatin or Carboplatin or paclitaxel or docetaxel as part of their standard

Description

Inclusion Criteria:

• All patients receiving chemotherapy for solid cancer
• Patient aged>18years

Exclusion Criteria:

• Age ≤ 18 years
• Pre-existing neuropathy
• Patients diagnosed with Psychiatric illness
• Patients with pre-existing peripheral neuropathy
• Patients taking medication for neuropathy
• Long standing diabetes (>10 years)
• Renal and Hepatic disease

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Baseline and after 4th cycle; Histopathologically diagnosed Solid Cancer Patients Planned for Platinum and Taxane based chemotherapy will be going for Neuropathy test- Nerve conduction test(NCV), vitamin D, B12 and Nox4 expression at Baseline and after 4th cycle of chemo	Drug: Cisplatin, Carboplatin, Paclitaxel, Docetaxel; Solid cancer Patients receiving any one drug or in combination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of different type and severity of Neuropathy in Solid Cancer Patients Undergoing Chemotherapy using Total Neuropathy Score(TNS) and Nerve conduction velocity study	Sensory symptoms, Motor Symptoms, Pin sensation, Vibration sensibility, Strength, Tendon reflexes will be recording using likert scale from 0 to 5 "0= None, 1= Limited to fingers or toes, 2= Extend to ankle or wrist, 3= Extend to knee or elbow, 4= Above knees/elbows".	Baseline and after 4th cycle of chemotherapy ( 3weekly cycle) 84 days
NOX4 Gene Expression in Blood of Solid Cancer Patients Undergoing Chemotherapy	The expression level of the NADPH oxidase 4 (NOX4) gene in blood will be measured using real time polymerase chain reaction (RT-PCR) to assess its potential role in chemotherapy-induced neuropathy. Ct-value of Nox4 gene will be normalized with reference gene GAPDH to calculate relative expression using 2-∆∆Ct method. Changes in NOX4 expression will be analyzed to understand its relationship with neuropathy development in solid cancer patients undergoing chemotherapy. Blood samples will be collected at baseline and after the fourth cycle of chemotherapy	at Baseline and after 4th cycle of chemotherapy (3weekly cycle) 84 days
Serum Vitamin D and Homocysteine Levels in Solid Cancer Patients Undergoing Chemotherapy	Serum levels of vitamin D and homocysteine will be measured using chemiluminescent immunoassay (CLIA) techniques to evaluate their potential association with chemotherapy-induced neuropathy. Vitamin D plays a role in nerve health, while elevated homocysteine levels have been linked to nerve damage. These biomarkers will be assessed to explore their correlation with neuropathy symptoms. Blood samples for vitamin D and homocysteine levels will be collected at baseline and after the fourth cycle of chemotherapy.	at baseline and after 4th cycle of chemotherapy ( 3weekly cycle) 84 days
serum catalase and malondialdehyde level in solid cancer patients undergoing chemotherapy	Catalase and Malondialdehyde will be measured using Enzyme linked immunosorbent assay (ELISA) to determine oxidative stress status.	at baseline and after 4th cycle of chemotherapy ( 3weekly cycle= 84 days)
Nerve conduction studies (NCS)	Sensory nerve studies: Median and ulnar nerve measurements like the amplitude (mV), conduction velocity (m/s) and distal latency (ms) will be recorded at wrist and interpretation will be done as demyelination when amplitude decreases or normal, velocity- decreases and Latency-increases; Axonal when amplitude-decreased, conduction velocity-normal and latency normal; Motor nerve studies: Median and ulnar nerve measurements like the amplitude (mV), conduction velocity (m/s) and distal latency (ms) will be recorded at wrist and elbow and interpretation will be done as demyelination when amplitude decreases or normal, velocity- decreases and Latency-increases; Axonal when amplitude-decreased, conduction velocity-normal and latency normal	at baseline and after 4th cycle of chemotherapy ( 3weekly cycle= 84 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measures peripheral neuropathy grade and quality of life using EORTC-QLQ-CIPN20	Chemotherapy-induced Peripheral Neuropathy 20 items" (EORTC-QLQ-CIPN20)) and analysis of clinical decision-making to assess the incidence, severity and interference of peripheral neuropathy. Scale of EORTC-QLQ-CIPN20: assess 20 items (sensory (9), motor (8), autonomic symptoms (3)) with the use of a 4-point Likert scale (1 = "Not at all", 2 = "A little", 3 = "Quite a bit", 4 = "Very much"	at baseline and after 4th cycle of chemotherapy ( 3weekly cycle= 84 days)

Collaborators and Investigators

• Sponsor: Swami Rama Himalayan University

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2022
• Primary Completion (Estimated): August 20, 2024
• Study Completion (Estimated): August 25, 2024

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: July 5, 2024
• First Posted (Actual): July 8, 2024

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Quality of Life; Vitamin B12; Homocysteine; NADPH oxidase 4; Chemotherapy induced Neuropathy; 25-Hydroxy Vitamin D; Proteomics profiling
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Docetaxel; Carboplatin; Paclitaxel
• Other Study ID Numbers: SRHU2022386

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: This will be done later with permission from research board

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No