A prospective, open label, 24-week trial of methylcobalamin in the treatment of diabetic polyneuropathy

Jacqueline C. Dominguez, Arlene R. Ng, Ludwig F. Damian

Institute for Neurosciences, St. Luke’s Medical Center, Quezon City, Philippines.

DOI: 10.4236/jdm.2012.24064                

Abstract

Introduction: Vitamin B complex has been used for peripheral neuropathy for a long time and continues to be part of current practice despite lack of strong evidence for its use and its non-inclusion in treatment guidelines. Objective: To determine the clinical and neurophysiological effects of 1500 μgm/day of oral methylcobalamin among subjects with diabetic polyneuropathy. Methodology: We conducted a prospective, open-label study on adult diabetic subjects with polyneuropathy who were given 1500 μgm/day of oral methylcobalamin over 24-weeks. The primary outcome measure was the Toronto Clinical Scoring System (CSS) and secondary measures were Subjective Impression of Change, Clinicians Impression of Change and neurophysiological parameters. Results: Out of forty eight subjects, thirty seven completed treatment and twenty one agreed to have repeat neurophysiologic study post-treatment. At the end of treatment, there was a significant decline in the Toronto CSS score (p < 0.0001) indicating improvement. This was observed across all stages of severity and in any duration of diabetes whether more or less than 10 years. The symptoms that improved compared to baseline and that did not emerge over the course of 24 weeks were tingling (p < 0.03), upper limb symptoms (p < 0.003), ataxia (p < 0.004), and signs of impaired position (P < 0.009) sense, vibration sense (p < 0.0001), pinprick sensation (p < 0.004) and knee reflex (p < 0.004). No significant improvement was seen in the secondary outcomes (both p=0.06) except for ulnar nerve amplitude and distal latency. Conclusion: This 24-week open label study demonstrated that symptoms of diabetic polyneuropathy significantly improved among subjects given methylcobalamin 1500 μgm/day and new symptoms did not emerge over the 24 week observation period. Larger controlled trials are needed to corroborate these findings.

Keywords

Methylcobalamin; Diabetic Polyneuropathy; Therapeutics; Clinical Trial

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Wild, S., Gojka, R., Green, A., Sicree, R. and King, H. (2004) Global prevalence of diabetes. Estimates for the year 2000 and projections for 2030. Diabetes Care, 27, 1047-1053. doi:10.2337/diacare.27.5.1047
[2]	Lu, B., Yang, Z., Wang, M., et al. (2010) High prevalence of diabetic neuropathy in population-based patients diagnosed with type 2 diabetes in the Shanghai downtown. Diabetes Research and Clinical Practice, 88, 289-294. doi:10.1016/j.diabres.2010.02.002
[3]	Ramirez M.A. and Borja N.L. (2008) Epalrestat: An aldose reductase inhibitor for the treatment of diabetic neuropathy. Pharmacotherapy, 28, 646-655. doi:10.1592/phco.28.5.646
[4]	Ziegler D., Nowak H., Kempler P., Vargha P. and Low, P.A. (2004) Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: A meta-analysis. Diabetic Medicine, 21, 114-121. doi:10.1111/j.1464-5491.2004.01109.x
[5]	Raskin, J., Pritchett, Y.L., Wang, F. et al. (2005) A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. Pain Medicine, 6, 346-356. doi:10.1111/j.1526-4637.2005.00061.x
[6]	Max, M.B., Lynch, S.A., Muir, J., Shoaf, S.E., Smoller, B. and Dubner, R. (1992) Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. The New England Journal of Medicine, 326, 1250-1256. doi:10.1056/NEJM199205073261904
[7]	Lesser, H., Sharma, U., LaMoreaux, L. and Poole, R.M. (2004) Pregabalin relieves symptoms of painful diabetic neuropathy: A randomized controlled trial. Neurology, 63, 2104-2110. doi:10.1212/01.WNL.0000145767.36287.A1
[8]	Raskin, P., Donofrio, P.D., Rosenthal, N.R. et al., the CAPSS-141 Study Group (2004) Topiramate vs placebo in painful diabetic neuropathy: Analgesic and metabolic effects. Neurology, 63, 865-873. doi:10.1212/01.WNL.0000137341.89781.14
[9]	Ang, C.D., Alviar, M.J.M., Dans, A.L. et al. (2008) Vitamin B for treating polyneuropathy. Cochrane Database Systematic Review, 3, Article No: CD004573. doi:10.1002/14651858.pub3.
[10]	England, J.D., Gronseth, G.S., Franklin, G., et al. (2005) Distal symmetric polyneuropathy: A definition for clinical research: Report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology, 64, 199-207. doi:10.1212/01.WNL.0000149522.32823.EA
[11]	Bril, V. and Perkins, B.A. (2002) Validation of the Toronto Clinical Scoring System in diabetic polyneuropathy. Diabetes Care, 25, 2048-2050. doi:10.2337/diacare.25.11.2048
[12]	Bril, V., England, J., Franklin, J.M. et al. (2011) Evidence-based guideline: Treatment of painful diabetic neuropathy. Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology, 76, 1. doi:10.1212/WNL.0b013e3182166ebe
[13]	Partanen, J., Niskanen, L., Lehtines, J., et al. (1995) Natural history of peripheral neuropathy in patients with non-insulin dependent diabetes mellitus. The New England Journal of Medicine, 333, 89-94. doi:10.1056/NEJM199507133330203
[14]	Watanabe, T., Kaji, R., Oka, N., Bara, W. and Kimura, J. (1994) Ultra-high dose methylcobalamin promotes nerve regeneration in experimental acrylamide neuropathy. J Neurol Sci, 122, 140-143. doi:10.1016/0022-510X(94)90290-9
[15]	Vinik, A.I. and Zeigler D. (2001) Diabetic cardiovascular autonomic neuropathy. Circulation, 115, 387-397. doi:10.1161/CIRCULATIONAHA.106.634949
[16]	Dyck, P.J., Davies, J.L., Litchy, W.J. and O’Brien, P.C. (1997) Longitudinal assessment of diabetic polyneuropathy using composite score in the Rochester Diabetic Neuropathy Study Cohort. Neurology, 49, 229-239. doi:10.1212/WNL.49.1.229
[17]	Maron, B.A. and Loscalzo, J. (2009) The treatment of hyperhomocysteinemia. Annual Review of Medicine, 60, 39-54. doi:10.1146/annurev.med.60.041807.123308
[18]	Yaqub, B.A., Siddique, A. and Sulimani, R. (1992) Effects of Methylcobalamin on diabetic neuropathy. Clinical Neurology and Neurosurgery, 9, 105-111.
[19]	Sun, Y., Lai, M.S., and Lu, C.J. (2005) Effectiveness of vitamin B12 on diabetic neuropathy: Systematic review of clinical controlled trials. Acta Neurol Taiwan, 14, 48-54.
[20]	Kuwabara, S., Nakazawa, R., Azuma, N, et al. (1999) Intravenous methylcobalamin treatment for uremic and diabetic neuropathy in chronic hemodialysis patients. Internal Medicine, 38, 472-475.