The Efficacy Of Intravenous Immunoglobulin Therapy In Treatment Induced Neuropathy Of Diabetes

Summary

The goal of this pilot study is to obtain preliminary data on the magnitude of the treatment effect of IVIG on the neuropathic pain and neuropathy severity associated with treatment induced neuropathy (TIND). The investigators hypothesize that immune globulin, administered intravenously (IVIG), will reduce the pain associated with treatment induced neuropathy and reduce the neuropathy severity. Treatment induced neuropathy in diabetes, is an iatrogenic complications of diabetes. The preliminary data will be used to power a larger treatment trial, and to aid the understanding of the mitigating factors in the treatment response.

Timeline

Start

2017-09-11

Primary completion

2022-02-01

Completion

2022-02-01

Publications

• Background Bril V. NIS-LL: the primary measurement scale for clinical trial endpoints in diabetic peripheral neuropathy. Eur Neurol. 1999;41 Suppl 1:8-13. doi: 10.1159/000052074.
• Background Chantelau E, Meyer-Schwickerath R, Klabe K. Downregulation of serum IGF-1 for treatment of early worsening of diabetic retinopathy: a long-term follow-up of two cases. Ophthalmologica. 2010;224(4):243-6. doi: 10.1159/000260231. Epub 2009 Nov 24.
• Background Dabby R, Sadeh M, Lampl Y, Gilad R, Watemberg N. Acute painful neuropathy induced by rapid correction of serum glucose levels in diabetic patients. Biomed Pharmacother. 2009 Dec;63(10):707-9. doi: 10.1016/j.biopha.2008.08.011. Epub 2008 Sep 16.
• Background Dotson S, Freeman R, Failing HJ, Adler GK. Hypoglycemia increases serum interleukin-6 levels in healthy men and women. Diabetes Care. 2008 Jun;31(6):1222-3. doi: 10.2337/dc07-2243. Epub 2008 Mar 10.
• Background Freeman R, Baron R, Bouhassira D, Cabrera J, Emir B. Sensory profiles of patients with neuropathic pain based on the neuropathic pain symptoms and signs. Pain. 2014 Feb;155(2):367-376. doi: 10.1016/j.pain.2013.10.023. Epub 2013 Oct 25.
• Background Gibbons C, Freeman R. The evaluation of small fiber function-autonomic and quantitative sensory testing. Neurol Clin. 2004 Aug;22(3):683-702, vii. doi: 10.1016/j.ncl.2004.03.002.
• Background Gibbons CH, Adler GK, Bonyhay I, Freeman R. Experimental hypoglycemia is a human model of stress-induced hyperalgesia. Pain. 2012 Nov;153(11):2204-2209. doi: 10.1016/j.pain.2012.06.030. Epub 2012 Aug 23.
• Background Gibbons CH, Freeman R. Treatment-induced diabetic neuropathy: a reversible painful autonomic neuropathy. Ann Neurol. 2010 Apr;67(4):534-41. doi: 10.1002/ana.21952.
• Background Gibbons CH, Freeman R. Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes. Brain. 2015 Jan;138(Pt 1):43-52. doi: 10.1093/brain/awu307. Epub 2014 Nov 11.
• Background Gibbons CH, Illigens BM, Wang N, Freeman R. Quantification of sweat gland innervation: a clinical-pathologic correlation. Neurology. 2009 Apr 28;72(17):1479-86. doi: 10.1212/WNL.0b013e3181a2e8b8.
• Background Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol. 1998 Jul;116(7):874-86. doi: 10.1001/archopht.116.7.874.
• Background Hilton P, Spathis GS, Stanton SL. Transient autonomic and sensory neuropathy in newly diagnosed insulin dependent diabetes mellitus. Br Med J (Clin Res Ed). 1983 Feb 26;286(6366):686. doi: 10.1136/bmj.286.6366.686. No abstract available.
• Background Honma H, Podratz JL, Windebank AJ. Acute glucose deprivation leads to apoptosis in a cell model of acute diabetic neuropathy. J Peripher Nerv Syst. 2003 Jun;8(2):65-74. doi: 10.1046/j.1529-8027.2003.03009.x.
• Background Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies IS, Polydefkis M, Smith AG, Sommer C, Valls-Sole J; European Federation of Neurological Societies; Peripheral Nerve Society. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010 Jul;17(7):903-12, e44-9. doi: 10.1111/j.1468-1331.2010.03023.x.
• Background Ohshima J, Nukada H. Hypoglycaemic neuropathy: microvascular changes due to recurrent hypoglycaemic episodes in rat sciatic nerve. Brain Res. 2002 Aug 23;947(1):84-9. doi: 10.1016/s0006-8993(02)02910-4.
• Background Razavi Nematollahi L, Kitabchi AE, Stentz FB, Wan JY, Larijani BA, Tehrani MM, Gozashti MH, Omidfar K, Taheri E. Proinflammatory cytokines in response to insulin-induced hypoglycemic stress in healthy subjects. Metabolism. 2009 Apr;58(4):443-8. doi: 10.1016/j.metabol.2008.10.018.
• Background Singleton JR, Bixby B, Russell JW, Feldman EL, Peltier A, Goldstein J, Howard J, Smith AG. The Utah Early Neuropathy Scale: a sensitive clinical scale for early sensory predominant neuropathy. J Peripher Nerv Syst. 2008 Sep;13(3):218-27. doi: 10.1111/j.1529-8027.2008.00180.x.
• Background Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010 Oct;33(10):2285-93. doi: 10.2337/dc10-1303.
• Background Tesfaye S, Malik R, Harris N, Jakubowski JJ, Mody C, Rennie IG, Ward JD. Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis). Diabetologia. 1996 Mar;39(3):329-35. doi: 10.1007/BF00418349.
• Background Tesfaye S, Vileikyte L, Rayman G, Sindrup SH, Perkins BA, Baconja M, Vinik AI, Boulton AJ; Toronto Expert Panel on Diabetic Neuropathy. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011 Oct;27(7):629-38. doi: 10.1002/dmrr.1225.
• Background Veves A, Backonja M, Malik RA. Painful diabetic neuropathy: epidemiology, natural history, early diagnosis, and treatment options. Pain Med. 2008 Sep;9(6):660-74. doi: 10.1111/j.1526-4637.2007.00347.x.
• Background Wang N, Gibbons CH. Skin biopsies in the assessment of the autonomic nervous system. Handb Clin Neurol. 2013;117:371-8. doi: 10.1016/B978-0-444-53491-0.00030-4.

Drugs

Indications