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

Acute Lymphoblastic Leukaemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03593304
• Other study ID #: No. BSMMU/2018/2105
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 29, 2018
• Est. completion date: March 30, 2019

Study information

• Verified date: July 2020
• Source: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 30, 2019
• Est. primary completion date: December 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukaemia
• Leukemia
• Leukemia, Lymphoid
• Neurotoxicity Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Vincristine Induced Neurotoxicity

Intervention

Drug:
• Injection Mecobalamin
Injection Mecobalamin (500mcg) three times a week (on day 1,3,5 of vincristine chemotherapy) for 5 weeks.
• Tablet Pyridoxine hydrochlorid
Tablet Pyridoxine hydrochloride (25 mg) 2 tablets thrice daily for 5 weeks.
• Normal saline
Injection Normal saline(1ml) three times a week (on day 1,3,5 of vincristine chemotherapy) for 5 weeks.
• Oral Placebo
Placebo Oral Tablet (25 mg) 2 tablets thrice daily for 5 weeks.

Locations

Country	Name	City	State
Bangladesh	Bangabandhu Sheikh Mujib Medical University	Dhaka	Shahbag
Bangladesh	Dhaka Medical College Hospital	Dhaka

Sponsors (1)

Lead Sponsor	Collaborator
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Country where clinical trial is conducted

Bangladesh, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Vincristine Induced neurotoxicity		Cumulative incidence at 5th week of vincristine chemotherapy
Primary	Severity of Vincristine Induced neurotoxicity	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
Primary	Time of onset of Vincristine Induced Neurotoxicity	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