Effect of Ambroxol in Diabetic Peripheral Neuropathy
Study Details
Study Description
Brief 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
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
N/A |
Detailed Description
All patients presenting to the Endocrinology department, Ain Shams University Hospitals, will be assessed for eligibility as follow:
Inclusion criteria:
-
Patients aged 18-75 years diagnosed with Type 2 Diabetes.
-
Patients diagnosed with Peripheral Diabetic Neuropathy.
Exclusion criteria:
-
Patients with autoimmune disorders (Sjogren's syndrome, lupus, rheumatoid arthritis),inherited disorders causing PN (Charcot-Marie-Tooth), thyroid diseases, patients undergone gastroplasty surgery and cancer patients.
-
Pressure on or injury to the nerves
-
Patients with severe kidney or liver dysfunction.
-
Patients with recent history of / or ongoing infection.
-
Patients with cerebral vascular disease, vasculitis, peripheral arterial disease or claudication symptoms, toxic neuritis, vitamin B12 or folate deficiency, spondyloarthropathy, foot edema or ulcer and diagnosis of other neuromuscular disorders or neurodegenerative diseases.
-
Use of medications or supplements known to cause peripheral neuropathy.
-
Patients consuming alcohol, any antioxidant supplements or anti-inflammatory medicines and drug abuse.
-
Ketoacidosis or hypoglycemia resulting in hospital admission within the last 3 months.
-
Pregnancy or lactation or expecting to get pregnant during the study.
-
Medical, psychological, behavioral or pharmacological factors interfering with ability to participate in trial, collection or interpretation of study data.
-
Allergy to ambroxol.
Eligible patients will be randomly assigned to one of 2 groups:
Group 1, Ambroxol group (n=40): Patients will receive conventional therapy for diabetic neuropathy in addition to ambroxol 450 mg/day divided into 3 doses (each dose consists of two 75mg tablets) daily for 3 months.
Group 2, Control group (n= 40): Patients will receive conventional therapy for diabetic neuropathy for 3 months.
All subjects will sign an informed consent statement prior to inclusion in the study.
Follow up evaluation :
All patients in both groups will be followed up every other week & will be assessed for the following:
Diabetic neuropathy scoring, occurrence of side effects & Pain assessment.
End of study evaluation :
After 3 months, all patients will be assessed for the same parameters assessed at baseline.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Ambroxol (intervention arm) 40 patients will receive conventional therapy for diabetic neuropathy in addition to ambroxol 450 mg/day divided into 3 doses (each dose consists of 2 75mg capsules) daily for 3 months. |
Drug: Ambroxol Oral Product
Drug: Ambroxol (75 mg capsule)
Ambroxol is a mucolytic and expectorant drug. Ambroxol has been approved as lozenges for topical analgesia of sore throat in pharyngitis owing to its local anesthetic properties. Anti-inflammatory properties of ambroxol were confirmed by numerous studies. Ambroxol affect neuronal transduction by blocking (TTX)-resistant Na+ channels (Nav1.8) in small (pain-sensing) dorsal root ganglion neurons more potently than TTX-sensitive channels.
|
No Intervention: Control arm 40 patients will receive conventional therapy for diabetic neuropathy for 3 months. |
Outcome Measures
Primary Outcome Measures
- Effect of Ambroxol on Tumor necrosis factor alpha (TNF-α) [3 months]
Blood samples will be drawn at baseline and end of study to track changes in TNF-α using ELISA technique
- Effect of Ambroxol on NF-κB (or NF-kappaB, "nuclear factor kappa-light-chain-enhancer of activated B cells") [3 months]
Blood samples will be drawn at baseline and end of study to track changes in NF-kappaB levels using ELISA technique
- Effect of Ambroxol on Superoxide dismutase [3 months]
Blood samples will be drawn at baseline and end of study to track changes in Superoxide dismutase levels using spectrophotometric technique
Secondary Outcome Measures
- Effect of Ambroxol on clinical outcome : Toronto clinical scoring systems (TCSS) [3 months]
Patient are going to be followed up every other week for detection of progression and severity of neuropathy.
- Effect of Ambroxol on clinical outcome : Michigan diabetic neuropathy score (MDNS) [3 months]
Patient are going to be followed up every other week for detection of progression and severity of neuropathy.
- Effect of Ambroxol on clinical outcome : Pain assessment using the Numeric rating scale NRS [3 months]
Patients are going to be followed up every other week to detect point decrease on pain scale
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients aged 18-75 years diagnosed with Type 2 Diabetes.
-
Patients diagnosed with Peripheral Diabetic Neuropathy.
Exclusion Criteria:
-
Patients with autoimmune disorders (Sjogren's syndrome, lupus, rheumatoid arthritis),inherited disorders causing PN (Charcot-Marie-Tooth), thyroid diseases, patients undergone gastroplasty surgery and cancer patients.
-
Pressure on or injury to the nerves
-
Patients with severe kidney or liver dysfunction.
-
Patients with recent history of / or ongoing infection.
-
Patients with cerebral vascular disease, vasculitis, peripheral arterial disease or claudication symptoms, toxic neuritis, vitamin B12 or folate deficiency, spondyloarthropathy, foot edema or ulcer and diagnosis of other neuromuscular disorders or neurodegenerative diseases.
-
Use of medications or supplements known to cause peripheral neuropathy.
-
Patients consuming alcohol, any antioxidant supplements or anti-inflammatory medicines and drug abuse.
-
Ketoacidosis or hypoglycemia resulting in hospital admission within the last 3 months.
-
Pregnancy or lactation or expecting to get pregnant during the study.
-
Medical, psychological, behavioral or pharmacological factors interfering with ability to participate in trial, collection or interpretation of study data.
-
Allergy to ambroxol.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Ain Shams university Hospital | Cairo | Egypt |
Sponsors and Collaborators
- Ain Shams University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
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- Association, American Diabetes.
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- 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.
- 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.
- 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.
- 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.
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- 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.
- 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
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- 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.
- 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.
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- Weiser T (2000) The secretolytic ambroxol blocks neuronal Na+channels. Soc Neurosci Abstr 454.14.
- 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.
- 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.
- 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.
- Ambroxol in DPN