Effect of Ambroxol in Diabetic Peripheral Neuropathy

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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Effect of Ambroxol on the Inflammatory Markers and Clinical Outcome of Patients With Diabetic Peripheral Neuropathy

Conditions
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Diabetic Neuropathy Peripheral

Intervention / Treatment
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* Drug: Ambroxol Oral Product


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ambroxol (intervention arm)<br>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<br>* 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.<br>|
| No Intervention: Control arm<br>40 patients will receive conventional therapy for diabetic neuropathy for 3 months. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Ambroxol on Tumor necrosis factor alpha (TNF-α) | Blood samples will be drawn at baseline and end of study to track changes in TNF-α using ELISA technique | 3 months | 
| Effect of Ambroxol on NF-κB (or NF-kappaB, nuclear factor kappa-light-chain-enhancer of activated B cells) | Blood samples will be drawn at baseline and end of study to track changes in NF-kappaB levels using ELISA technique | 3 months | 
| Effect of Ambroxol on Superoxide dismutase | Blood samples will be drawn at baseline and end of study to track changes in Superoxide dismutase levels using spectrophotometric technique | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Ambroxol on clinical outcome : Toronto clinical scoring systems (TCSS) | Patient are going to be followed up every other week for detection of progression and severity of neuropathy. | 3 months | 
| Effect of Ambroxol on clinical outcome : Michigan diabetic neuropathy score (MDNS) | Patient are going to be followed up every other week for detection of progression and severity of neuropathy. | 3 months | 
| Effect of Ambroxol on clinical outcome : Pain assessment using the Numeric rating scale NRS | Patients are going to be followed up every other week to detect point decrease on pain scale | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Complications, Diabetic Peripheral Neuropathy, Inflammatory markers, Tumor necrosis alpha, nuclear factor kappa-light-chain-enhancer of activated B cells, Oxidative stress, Superoxide dismutase