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

Sponsor

Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh (Other)

Overall Status

Completed

CT.gov ID

NCT03593304

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Vincristine Induced Neurotoxicity Acute Lymphoblastic Leukaemia	Drug: Injection Mecobalamin Drug: Tablet Pyridoxine hydrochlorid Drug: Normal saline Drug: Oral Placebo	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Experimental group: Medicine- Injection Mecobalamin (500mcg), Tablet Pyridoxine hydrochloride (25 mg) Placebo group: Injection normal saline (1ml), oral placebo pillExperimental group: Medicine- Injection Mecobalamin (500mcg), Tablet Pyridoxine hydrochloride (25 mg) Placebo group: Injection normal saline (1ml), oral placebo pill

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Mar 29, 2018

Actual Primary Completion Date :

Dec 30, 2018

Actual Study Completion Date :

Mar 30, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Incidence of Vincristine Induced neurotoxicity [Cumulative incidence at 5th week of vincristine chemotherapy]
Severity of Vincristine Induced neurotoxicity [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
Time of onset of Vincristine Induced Neurotoxicity [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)