Effect of Ambroxol in Diabetic Peripheral Neuropathy

Summary

A prospective, randomized, controlled study will be conducted at Department of Endocrinology, Faculty of Medicine, Ain Shams University, assessing the efficacy of Ambroxol addition on the clinical outcome and inflammatory markers in Diabetic peripheral neuropathy patients

Timeline

Start

2022-10-01

Primary completion

2023-10

Completion

2023-11

Publications

• Background Association, American Diabetes.
• Background Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D, Williams R; IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019 Nov;157:107843. doi: 10.1016/j.diabres.2019.107843. Epub 2019 Sep 10.
• Background Candrilli SD, Davis KL, Kan HJ, Lucero MA, Rousculp MD. Prevalence and the associated burden of illness of symptoms of diabetic peripheral neuropathy and diabetic retinopathy. J Diabetes Complications. 2007 Sep-Oct;21(5):306-14. doi: 10.1016/j.jdiacomp.2006.08.002.
• Background Gregg EW, Sorlie P, Paulose-Ram R, Gu Q, Eberhardt MS, Wolz M, Burt V, Curtin L, Engelgau M, Geiss L; 1999-2000 national health and nutrition examination survey. Prevalence of lower-extremity disease in the US adult population >=40 years of age with and without diabetes: 1999-2000 national health and nutrition examination survey. Diabetes Care. 2004 Jul;27(7):1591-7. doi: 10.2337/diacare.27.7.1591.
• Background Albers JW, Pop-Busui R. Diabetic neuropathy: mechanisms, emerging treatments, and subtypes. Curr Neurol Neurosci Rep. 2014 Aug;14(8):473. doi: 10.1007/s11910-014-0473-5.
• Background Boulton AJ, Malik RA. Diabetic neuropathy. Med Clin North Am. 1998 Jul;82(4):909-29. doi: 10.1016/s0025-7125(05)70029-8.
• Background Soliman E,Gellido C.Diabetic Neuropathy. eMedicine.com March 29, 2002.
• Background Ang L, Cowdin N, Mizokami-Stout K, Pop-Busui R. Update on the Management of Diabetic Neuropathy. Diabetes Spectr. 2018 Aug;31(3):224-233. doi: 10.2337/ds18-0036.
• Background Boulton AJ, Malik RA, Arezzo JC, Sosenko JM. Diabetic somatic neuropathies. Diabetes Care. 2004 Jun;27(6):1458-86. doi: 10.2337/diacare.27.6.1458. No abstract available.
• Background Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D; American Diabetes Association. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005 Apr;28(4):956-62. doi: 10.2337/diacare.28.4.956. No abstract available.
• Background Dyck PJ, Albers JW, Andersen H, Arezzo JC, Biessels GJ, Bril V, Feldman EL, Litchy WJ, O'Brien PC, Russell JW; Toronto Expert Panel on Diabetic Neuropathy. Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev. 2011 Oct;27(7):620-8. doi: 10.1002/dmrr.1226.
• Background Thomas PK. Classification, differential diagnosis, and staging of diabetic peripheral neuropathy. Diabetes. 1997 Sep;46 Suppl 2:S54-7. doi: 10.2337/diab.46.2.s54.
• Background American Diabetes Association. Standardized measures in diabetic neuropathy. Diabetes Care 1996;19(1S):72S-92S.
• Background Pang L, Lian X, Liu H, Zhang Y, Li Q, Cai Y, Ma H, Yu X. Understanding Diabetic Neuropathy: Focus on Oxidative Stress. Oxid Med Cell Longev. 2020 Jul 31;2020:9524635. doi: 10.1155/2020/9524635. eCollection 2020.
• Background Elmarakby AA, Sullivan JC. Relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy. Cardiovasc Ther. 2012 Feb;30(1):49-59. doi: 10.1111/j.1755-5922.2010.00218.x. Epub 2010 Aug 16.
• Background Sandireddy R, Yerra VG, Areti A, Komirishetty P, Kumar A. Neuroinflammation and oxidative stress in diabetic neuropathy: futuristic strategies based on these targets. Int J Endocrinol. 2014;2014:674987. doi: 10.1155/2014/674987. Epub 2014 Apr 30.
• Background Kasznicki J, Kosmalski M, Sliwinska A, Mrowicka M, Stanczyk M, Majsterek I, Drzewoski J. Evaluation of oxidative stress markers in pathogenesis of diabetic neuropathy. Mol Biol Rep. 2012 Sep;39(9):8669-78. doi: 10.1007/s11033-012-1722-9. Epub 2012 Jun 21.
• Background Ganesh Yerra V, Negi G, Sharma SS, Kumar A. Potential therapeutic effects of the simultaneous targeting of the Nrf2 and NF-kappaB pathways in diabetic neuropathy. Redox Biol. 2013 Aug 1;1(1):394-7. doi: 10.1016/j.redox.2013.07.005.
• Background Sheikh, W. M. E., Alahmar, I. E., Salem, G. M., & El-Sheikh, M. A. (2019). Tumor necrosis factor alpha in peripheral neuropathy in type 2 diabetes mellitus. Egyptian Journal of Neurology, Psychiatry and Neurosurgery, 55(1), 1-7. https://doi.org/10.1186/s41983-019-0080-0
• Background Heidari N, Sajedi F, Mohammadi Y, Mirjalili M, Mehrpooya M. Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy. J Pain Res. 2019 Nov 19;12:3147-3159. doi: 10.2147/JPR.S228255. eCollection 2019.
• Background Vallianou N, Evangelopoulos A, Koutalas P. Alpha-lipoic Acid and diabetic neuropathy. Rev Diabet Stud. 2009 Winter;6(4):230-6. doi: 10.1900/RDS.2009.6.230. Epub 2009 Dec 30.
• Background Beeh KM, Beier J, Esperester A, Paul LD. Antiinflammatory properties of ambroxol. Eur J Med Res. 2008 Dec 3;13(12):557-62.
• Background Su X, Wang L, Song Y, Bai C. Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide. Intensive Care Med. 2004 Jan;30(1):133-40. doi: 10.1007/s00134-003-2001-y. Epub 2003 Sep 20.
• Background Xia DH, Xi L, Xv C, Mao WD, Shen WS, Shu ZQ, Yang HZ, Dai M. The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor beta1 and tumor necrosis factor alpha. Med Oncol. 2010 Sep;27(3):697-701. doi: 10.1007/s12032-009-9271-3. Epub 2009 Jul 28.
• Background Sunkari S, Thatikonda S, Pooladanda V, Challa VS, Godugu C. Protective effects of ambroxol in psoriasis like skin inflammation: Exploration of possible mechanisms. Int Immunopharmacol. 2019 Jun;71:301-312. doi: 10.1016/j.intimp.2019.03.035. Epub 2019 Mar 29.
• Background Puschmann S, Engelhorn R. [Pharmacological study on the bromhexine metabolite ambroxol (author's transl)]. Arzneimittelforschung. 1978;28(5a):889-98. No abstract available. German.
• Background Schutz A, Gund HJ, Pschorn U, Aicher B, Peil H, Muller A, de Mey C, Gillissen A. Local anaesthetic properties of ambroxol hydrochloride lozenges in view of sore throat. Clinical proof of concept. Arzneimittelforschung. 2002;52(3):194-9. doi: 10.1055/s-0031-1299879.
• Background Weiser T (2000) The secretolytic ambroxol blocks neuronal Na+channels. Soc Neurosci Abstr 454.14.
• Background Weiser T, Wilson N. Inhibition of tetrodotoxin (TTX)-resistant and TTX-sensitive neuronal Na(+) channels by the secretolytic ambroxol. Mol Pharmacol. 2002 Sep;62(3):433-8. doi: 10.1124/mol.62.3.433.
• Background Weiser T. Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant Nav1.2 channels. Neurosci Lett. 2006 Mar 13;395(3):179-84. doi: 10.1016/j.neulet.2005.10.058. Epub 2005 Nov 15.
• Background Gaida W, Klinder K, Arndt K, Weiser T. Ambroxol, a Nav1.8-preferring Na(+) channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain. Neuropharmacology. 2005 Dec;49(8):1220-7. doi: 10.1016/j.neuropharm.2005.08.004. Epub 2005 Sep 21.
• Background Pawlinski L, Krawczyk M, Fiema M, Tobor E, Kiec-Wilk B. Dual-action ambroxol in treatment of chronic pain in Gaucher Disease. Eur J Pain. 2020 May;24(5):992-996. doi: 10.1002/ejp.1538. Epub 2020 Mar 9.
• Background Kern KU, Weiser T. Topical ambroxol for the treatment of neuropathic pain. An initial clinical observation. Schmerz. 2015 Dec;29 Suppl 3(Suppl 3):S89-96. doi: 10.1007/s00482-015-0060-y.
• Background Mullin S, Smith L, Lee K, D'Souza G, Woodgate P, Elflein J, Hallqvist J, Toffoli M, Streeter A, Hosking J, Heywood WE, Khengar R, Campbell P, Hehir J, Cable S, Mills K, Zetterberg H, Limousin P, Libri V, Foltynie T, Schapira AHV. Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial. JAMA Neurol. 2020 Apr 1;77(4):427-434. doi: 10.1001/jamaneurol.2019.4611.
• Background Narita A, Shirai K, Itamura S, Matsuda A, Ishihara A, Matsushita K, Fukuda C, Kubota N, Takayama R, Shigematsu H, Hayashi A, Kumada T, Yuge K, Watanabe Y, Kosugi S, Nishida H, Kimura Y, Endo Y, Higaki K, Nanba E, Nishimura Y, Tamasaki A, Togawa M, Saito Y, Maegaki Y, Ohno K, Suzuki Y. Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study. Ann Clin Transl Neurol. 2016 Feb 2;3(3):200-15. doi: 10.1002/acn3.292. eCollection 2016 Mar.

Drugs

Indications