Neuroprotective Effect of Vitamin B12 and Vitamin B6 Against Vincristine Induced Peripheral Neuropathy
Condition: Vincristine Induced Peripheral Neuropathy (VIPN)
MeSH terms: Peripheral Nervous System Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      This study will be conducted to evaluate the effect of vitamin B12 and vitamin B6 in delaying
      the onset and reducing the incidence and severity of Vincristine Induced Peripheral
      Neuropathy (VIPN) in Acute Lymphoblastic Leukemia (ALL) patient.
    

Detailed description: 
      Acute Lymphoblastic Leukemia (ALL) is an emerging health burden for Bangladesh. It is
      anticipated that about 20 million people are going to be affected annually by 2025 in
      countries currently on developmental transition. Good prognostic outcome of ALL relies on
      uninterrupted and complete course of chemotherapy. About 85% of adult patients and 98% of
      children attain complete recovery with full course of treatment. One of the crucial
      chemotherapeutic agents used to treat ALL is vincristine. It is needed to complete
      vincristine with adequate dose in order to get a better prognostic outcome. About 45% of the
      patients getting vincristine develop a deleterious side effect called Vincristine Induced
      Peripheral Neuropathy (VIPN). Unfortunately, development of VIPN results in dose reduction,
      protocol deviation and even abandonment of treatment with vincristine in some ALL patients.
      Better prognostic outcome becomes an arcadia. So far, many researches have been conducted to
      explore a way to prevent or treat VIPN. But still no conclusive recommendation can be made.
      Therefore, VIPN has become an important issue need to be addressed. This study will be a
      small effort to identify the potential of vitamin B12 and vitamin B6 as probable preventive
      measures of VIPN. Evidence suggests that, vitamin B12 and vitamin B6 two water soluble, non
      toxic vitamins well recognized for the treatment of peripheral neuropathy. Vitamin B12 plays
      a very fundamental role in neurological function. It exerts its physiological effects through
      mediating two principal enzymatic pathways by which it maintains the integrity of neuronal
      membrane. On the other hand, vitamin B6 or pyridoxine is an essential co- factor in various
      synthesis pathways including synthesis of myelin sheath. Patients will be randomly allocated
      into two arms by using online research randomizer and newly diagnosed ALL patients will be
      enrolled in this research. From the day of starting chemotherapy, patients on arm A
      (Intervention arm) will be concurrently administered with vitamin B12 and vitamin B6. Vitamin
      B12 will be given 500 μg three times a week intravenously on a basis of every alternate day
      except the day of receiving vincristine and vitamin B6 will be given 50 mg thrice daily
      orally during the induction period (5 weeks) of chemotherapy cycle. On the other hand,
      patients on arm B (Placebo arm) will be given placebo pill and intravenous placebo injection
      at same interval. Prior to initiation of induction chemotherapy each participant will undergo
      neuropathy evaluation per National Cancer Institute's Common Terminology Criteria for Adverse
      Events (NCI-CTCAE) v.4.0 scale and will be interviewed according to the neurotoxicity
      subscale of Functional Assessment of Cancer Therapy (FACT) -GOG- Ntx quality of life
      assessment questionnaire. The participants will be re-evaluated once weekly on the outset of
      2nd week, 3rd week, 4th and 5th week of vincristine chemotherapy during induction period.
      They will be assessed per NCI-CTCAE v.4.0 scale for severity of neuropathy and by FACT- GOG-
      Ntx by answering specific questions regarding the presence of tingling, numbness, pain,
      muscle weakness and motor activities. As neuropathy and neuropathic pain are mostly
      subjective issue rather than objective and reflected more comprehensively by the particular
      person encountering with, so patient based measures will be used in this study. Incidence,
      onset and severity of peripheral neuropathy will be compared on both arms.
    

Intervention name(s): Injection Mecobalamin,; Tablet Pyridoxine hydrochloride; Intravenous normal saline 1 ml; Placebo pill
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Injection Mecobalamin (500mcg) three times a week (day 1, 3 and 5 of vincristine chemotherapy) for 5 weeks.; Tab. Pyridoxine hydrochloride (25 mg) 2 tablets thrice daily for 5 weeks; Normal saline 1 ml three times a week (day 1, 3 and 5 of vincristine chemotherapy) for 5 weeks; Placebo pill orally thrice daily for 5 weeks
Other intervention name(s): Vitamin B12; Vitamin B6; Normal saline; Placebo
Intervention MeSH terms: Vitamins; Vitamin B 12; Pyridoxine; Vitamin B 6; Vitamin B Complex
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention