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CTRI Number  CTRI/2024/05/068162 [Registered on: 31/05/2024] Trial Registered Prospectively
Last Modified On: 31/05/2024
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   To find out the effect of vitamin B6 and vitamin E in preventing neurological side effects caused due to cancer drug vincristine in children with blood cancer in first cycle of chemotherapy 
Scientific Title of Study   Impact of pyridoxine and vitamin E combination in preventing vincristine associated neurotoxicity in paediatric patients with hematolymphoid malignancies during induction phase of chemotherapy: A Randomized Control Trial 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Singh Neelam Vijayshankar 
Designation  PG student 
Affiliation  Jawaharlal Nehru Medical College, KLE University 
Address  Department of Paediatrics, Jawaharlal Nehru Medical College, KLE hospital road, Nehru Nagar

Belgaum
KARNATAKA
590010
India 
Phone  8291666917  
Fax    
Email  neelamsingh21ns@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Abhilasha Sampagar 
Designation  Professor 
Affiliation  Jawaharlal Nehru Medical College, KLE University 
Address  Paediatric Hematologist Oncologist,Department of Medical oncology, Jawaharlal Nehru Medical College, KLE Hospital road, Nehru Nagar

Belgaum
KARNATAKA
590010
India 
Phone  9686187023  
Fax    
Email  abhilasha.pedia@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Abhilasha Sampagar 
Designation  Professor 
Affiliation  Jawaharlal Nehru Medical College, KLE University 
Address  Paediatric Hematologist Oncologist,Department of Medical oncology, Jawaharlal Nehru Medical College, KLE Hospital road, Nehru Nagar

Belgaum
KARNATAKA
590010
India 
Phone  9686187023  
Fax    
Email  abhilasha.pedia@gmail.com  
 
Source of Monetary or Material Support  
KLEs Dr Prabhakar Kore Hospital, Jawaharlal Nehru Medical College, KLE University, Belagavi, Karnataka 590010, India 
 
Primary Sponsor  
Name  Dr Singh Neelam Vijayshankar 
Address  Department of Paediatrics, Jawaharlal Nehru Medical College, KLE Hospital road, Nehru Nagar, Belgaum, Karnataka,590010 India 
Type of Sponsor  Other [Principal Investigator] 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Singh Neelam Vijayshankar  KLEs Dr Prabhakar kore hospital, belgavi  Department of Paediatrics, Jawaharlal Nehru Medical Colleg, Nehru Nagar, KLE hospital road, Belagavi
Belgaum
KARNATAKA 
8291666917

neelamsingh21ns@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
JNMC institutional ethics committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C910||Acute lymphoblastic leukemia [ALL],  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Effect of vitamin E and viatmin B6 combination versus placebo drug  Capsule Vitamin E of dosage 40mg/kg orally for 35 days and tab vitamin B6 150mg/m2 orally for 35 days, these 2 drug combination versus placebo drug once a day, orally for 35 days will be given in paediatric patients with ALL in induction phase of chemotherapy . 
Intervention  Vitamin E and vitamin B6  Patients will be randomized into two groups. Intervention arm from day 1 will be subjected to combination of vitamin E 40mg/kg and vitamin B6 150mg/m2 along with induction chemotherapy. Placebo arm from day 1 will receive placebo drug along with induction chemotherapy. Capsule vitamin E of dosage 40mg/kg will be given orally for 35 days. Tab Vitamin B6, dose will be 150mg/m2, will be given orally for 35 days. 
 
Inclusion Criteria  
Age From  1.00 Year(s)
Age To  18.00 Year(s)
Gender  Both 
Details  All newly diagnosed case of paediatric ALL and lymphoid lymphoma between 1 to 18 years 
 
ExclusionCriteria 
Details  1. Patients diagnosed with CNS leukemia
2. Patients who are on anti-convulsant like gabapentin, lamotrigine, levetiracetam, lorazepam,, midazolam, carbamazepine
3. Patients who are on anti depressants like fluoxetine, fluvoxamine, sertraline, olanzapine
4 Established neurological condition like CP
5 Patients on therapeutic dose of azoles 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   On-site computer system 
Blinding/Masking   Participant Blinded 
Primary Outcome  
Outcome  TimePoints 
To determine the efficacy of pyridoxine and vitamin E combination in preventing vincristine induced neurotoxicity in paediatric patients with ALL and lymphoid lymphoma during induction phase of chemotherapy  Study will be conducted over a period of 1 year. 
 
Secondary Outcome  
Outcome  TimePoints 
1 to determine incidence of chemotherapy related toxicity during induction phase of chemotherapy

2 To compare common terminology criteria for adverse events (CTCAE) and total neuropathy score -pediatric vincristine (TNSPV) with electrodiagnosis testing in assessing VCR induced neurotoxicity 
Study will be conducted over a period of 1 year. 
 
Target Sample Size   Total Sample Size="40"
Sample Size from India="40" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   14/06/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

Leukemia’s  account for approximately 40-50% of childhood cancer burden in India with acute lymphoblastic leukemia being the commonest type. Acute lymphoblastic leukemia accounts for approximately 77% of cases of childhood leukemias. Lymphoblastic lymphoma accounts for 30-40 % . The recent advances in the treatment of leukemia and lymphoblastic lymphoma have resulted in significant improvement in cure rate of childhood malignancies but treatment related morbidities are still a challenge.   Treatment of ALL and lymphoblastic lymphoma  consists of 5 phases, which includes, Induction, Consolidation, Interim maintenance, Delayed intensification and Maintenance. First phase also known as remission induction, involves treatment for approximately 4 weeks depending on different protocols. This is the most important phase which aims to eradicate the malignant cells from bone marrow thus restoring normal hematopoiesis. The drugs used in this phase are vincristine, l-asparginase, daunorubicin, intrathecal methotrexate and steroids.Chemotherapeutic regimen completion with proper dose and adequate duration is crucial in determining the survival of patients with ALL and lymphoblastic lymphoma. Unfortunately, chemotherapy related toxicities significantly limits the dose and numbers of chemotherapy and may lead to interruption, dose reduction or even premature termination of treatment thus jeopardizing the treatment outcome.  Vincristine associated neurotoxicities are one of the most challenging and complex complications of chemotherapy .Vincristine  are Vinca alkaloids, a class of microtubule targeting agent that interferes with continuous mitotic  divison and cell growth of cancer cells. It is one of the most neurotoxic antineoplastic medicines.  Vincristine induced peripheral neurotoxicity (VIPN) is common side effect in paediatric cancer patients accounting for 45% of neuropathy incidence. Vincristine causes central nervous system and cranial nerves toxicities like ptosis, opthalmoplegia, blindness, blurred vison, diplopia, ocular muscle paresis, ototoxicity, SIADH, seizure. Muscular weakness in lower extremities, constipation, jaw pain, hoarseness were some of the other toxicities. VIPN develops due to neurodegenerative and oxidative stress. Moreover, neurotoxicity has negative impact on patient’s quality of life. Several measures like glutamic acid, B12, amitriptyline, pyridoxine and pyridostigmine have been used to treat vincristine induced peripheral neuropathy(VIPN). However, there is paucity of literature regarding the role of vitamin E and pyridoxine combination in prevention of VIPN. Vitamin B6 is an essential cofactor in synthesis of myelin sheath. It also has antioxidant property. There have been several randomized phase II studies looking at Vitamin E as neuroprotective agent. So we plan this study to determine whether vitamin B6 and vitamin E can prevent and or reduce the severity of vincristine induced neurotoxicity during induction phase of ALL and lymphoblastic lymphoma  which can eventually reduce treatment interruptions and morbidities during the most crucial phase of treatment, thus improving the treatment outcome.

 

 
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