Evaluate the Neuroprotective Effect of Vitamin B6 and Vitamin B12 Against Vincristine Induced Neurotoxicity in Acute Lymphoblastic Leukaemia Patients

July 7, 2020 updated by: Ferdaush Ahmed Sojib, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Randomized, Double-blind, Placebo Controlled, Multicenter Trial to Evaluate the Neuroprotective Effect of Vitamin B6 and Vitamin B12 Against Vincristine Induced Neurotoxicity in Acute Lymphoblastic Leukaemia Patients

This study will be conducted to evaluate the effect of vitamin B6 and vitamin B12 in reducing the incidence and severity and delaying the onset of Vincristine Induced neurotoxicity in Acute Lymphobalstic Leukemia (ALL) patient.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Acute lymphoblastic leukaemia (ALL) is increasing day by day in less developed countries like Bangladesh. Vincristine is one of the important chemotherapeutic agents used in combination with other medicines to treat Acute Lymphoblastic Leukemia (ALL). Good prognostic outcome of ALL depends on uninterrupted and complete course of chemotherapy. With full course of treatment about 85% of adult patients and 98% of children attain complete recovery. Development of some deleterious adverse effects especially neurotoxicity results in dose reduction, protocol deviation and even abandonment of treatment. About 45% patients develop peripheral neuropathy and more than 33% patients develop autonomic neuropathy who needs dose reduction or treatment protocol deviation. Many studies have been conducted to explore the potential of medicine to prevent or treat neuropathy but still there is no success. This proposed study will be an effort to identify the potential of vitamin B6 (Pyridoxine hydrochloride) and vitamin B12 (Mecobalamin) as preventive measure in reducing the incidence, risk, severity and time of onset of vincristine induced neurotoxicity. This study will be a multicenter, double blind, randomized controlled trial. In this study newly diagnosed ALL patients will be enrolled in induction phase and patients will be randomly allocated into two arms by using online graph pad software. After assessing the baseline characteristics by Eastern Cooperative Oncology Group (ECOG) performance status and Composite Autonomic Symptom Score (COMPASS 31), patient will be provided medicine or placebo. From the day of starting chemotherapy, patients on intervention arm will be administered vitamin B6 and vitamin B12. Vitamin B6 will be given 50 mg thrice daily orally for 5 weeks and Vitamin B12 will be given 500 μg three times weekly intravenously on day 1, 3 and 5 of every week for 5 weeks. On the other hand, patients on placebo arm will be given placebo pill and injection at same interval. Each patient will be evaluated for neurotoxicity on the outset of every 2nd, 3rd, 4th and 5th week by using COMPASS 31 for autonomic neuropathy. Incidence, severity and onset will be compared on both arms. After approval from institutional review board (IRB) every eligible patient will be informed about the intervention and the study. Informed written consent will be taken of the patients who will take part in the study willingly. Patient's anonymity will be maintained and will be used for research purpose only.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2
  • Phase 3

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

  • Bangladesh
      • Dhaka, Bangladesh
        • Dhaka Medical College Hospital
    • Shahbag
      • Dhaka, Shahbag, Bangladesh, 1000
        • Bangabandhu Sheikh Mujib Medical University

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

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • All patients, 18 years of age or older with newly diagnosed ALL going to start induction chemotherapy with Vincristine
  • Patients ECOG Performance Status 0 to 3
  • Patients with no preexisting autonomic neuropathy
  • Patients with normal renal function (Serum creatinine <1.5 mg/dl)
  • No history of diabetes mellitus
  • Patients agree to participate in the study signing an informed written consent

Exclusion Criteria:

  • Pregnant women and nursing mothers
  • Patients with clinical neuropathy due to diabetes mellitus and other causes like multiple sclerosis, spinal cord injury, post stroke
  • Patients with head neck tumors
  • Patients taking anticonvulsants, antidepressants, opioids, vitamin E and other neuropathic pain medication agents like topical anesthetic agents, non steroidal anti-inflammatory drugs (NSAIDs)

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Experimental:Mecobalamin and Pyridoxine hydrochloride
Injection Mecobalamin (500mcg) three times a week (on day 1,3,5 of vincristine chemotherapy) for 5 weeks.Tablet Pyridoxine hydrochloride (25 mg) 2 tablets thrice daily for 5 weeks.
Drug: Injection Mecobalamin
Injection Mecobalamin (500mcg) three times a week (on day 1,3,5 of vincristine chemotherapy) for 5 weeks.
Other Names:
  • Vitamin B12
Drug: Tablet Pyridoxine hydrochlorid
Tablet Pyridoxine hydrochloride (25 mg) 2 tablets thrice daily for 5 weeks.
Other Names:
  • Vitamin B6
Placebo Comparator: Placebo: normal saline and Oral placebo
Injection normal saline (1ml) three times a week (on day 1,3,5 of vincristine chemotherapy) for 5 weeks.Oral placebo pill 2 tablets thrice daily for 5 weeks.
Drug: Normal saline
Injection Normal saline(1ml) three times a week (on day 1,3,5 of vincristine chemotherapy) for 5 weeks.
Other Names:
  • Placebo for mcobalamin
Drug: Oral Placebo
Placebo Oral Tablet (25 mg) 2 tablets thrice daily for 5 weeks.
Other Names:
  • Placebo for pyridoxine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Vincristine Induced neurotoxicity
Time Frame: Cumulative incidence at 5th week of vincristine chemotherapy
Cumulative incidence at 5th week of vincristine chemotherapy
Severity of Vincristine Induced neurotoxicity
Time Frame: On the outset of 1st week change in the severity of neurotoxicity on the outset of 2nd week, 3rd week, 4th week, 5th week of vincristine chemotherapy
Changes of severity will be assessed by COMPASS 31 on the outset of 2nd week, 3rd week, 4th week, 5th week of vincristine chemotherapy
On the outset of 1st week change in the severity of neurotoxicity on the outset of 2nd week, 3rd week, 4th week, 5th week of vincristine chemotherapy
Time of onset of Vincristine Induced Neurotoxicity
Time Frame: 1st week (baseline), change in neurotoxicity status on the outset 2nd week, 3rd week, 4th week and 5th week of vincristine chemotherapy
change in neurotoxicity status on the outset of 2nd week, 3rd week, 4th week, 5th week of vincristine chemotherapy
1st week (baseline), change in neurotoxicity status on the outset 2nd week, 3rd week, 4th week and 5th week of vincristine chemotherapy

Collaborators and Investigators

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

Sponsor

Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

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)

March 29, 2018

Primary Completion (Actual)

December 30, 2018

Study Completion (Actual)

March 30, 2019

Study Registration Dates

First Submitted

March 10, 2018

First Submitted That Met QC Criteria

July 10, 2018

First Posted (Actual)

July 20, 2018

Study Record Updates

Last Update Posted (Actual)

July 8, 2020

Last Update Submitted That Met QC Criteria

July 7, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • No. BSMMU/2018/2105

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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