A Study on the Safety and Efficacy of Nitric Oxide Gel in Subjects With Painful Diabetic Neuropathy

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, 2-period crossover, 12-week trial to be conducted in 50 subjects with painful diabetic neuropathy. The objective of this trial is to assess the safety and efficacy of NO gel, a NO donor, as compared with a placebo gel, in symptom relief of subjects with painful diabetic neuropathy.

Detailed Description
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Neuropathic pain is a common symptom of diabetic neuropathy, and predominantly involves the lower limbs. Current strategies for the management of painful diabetic neuropathy include improved glycemic control, use of analgesics and addition of tricyclic antidepressants and anticonvulsants. However, many patients experience unsatisfactory responses and some undesired side effects. Considerable evidence implicates impaired nitric oxide synthesis plays an important role in the pathogenesis of diabetic neuropathic pain. Several small studies have shown that topical nitroglycerin ointment has local vasodilating properties, and a previous study has demonstrated that isosorbide dinitrate in spray form as a nitric oxide donor relieved some neuropathic symptoms in patients with painful diabetic neuropathy. Based on the findings, the investigators hypothesize that nitric oxide gel could be used as an alternative pain-relieving agent for patients with resistant diabetic neuropathic pain.

Official Title
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A Study on the Safety and Efficacy of Nitric Oxide Gel in Subjects With Painful Diabetic Neuropathy

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Drug: nitric oxide gel
* Drug: placebo gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects>=30 and<=80 years of age. Subjects with type 1 or type 2 diabetes mellitus with painful diabetic neuropathy. Subjects without undergoing treatment for painful diabetic neuropathy or with treatment for at least 3 months but still presenting neuropathic pain prior to randomization. Subjects who are healthy without any serious diseases that require hospitalization during the study period. Subjects who are capable of understanding and having signed the Informed Consent Form after detailed description of the treatment procedures and potential risks and benefits. Exclusion Criteria: Subjects with diagnosis of cancer and are still on active therapies. Subjects with diagnosis of an active disease (e.g. hyper-or-hypothyroidism, advanced chronic renal failure, severe anemia, liver cirrhosis, active infectious disease etc.) and are still under regular treatment for this disease Subjects with peripheral neuropathy caused by a known acute or chronic disease or injury Subjects who are on other medications with pharmacological actions that may lead to excessive formation of nitric oxide (e.g. sublingual nitroglycerin, sildanafil etc.) or may accentuate drug effects due to excessive formation of nitric oxide. Subjects with severe peripheral artery disease leading to absence of foot pulses. Subjects with erratic glycemic control (HbA1c 12). Subjects with an active foot ulceration or infection. Subjects with any known allergic reaction to any ingredient in the 2 gel preparations. Subjects who have been enrolled into any clinical study in the preceding 3 months prior to randomization. Subjects with current substance or alcohol abuse that in the opinion of the investigator would interfere with compliance or with interpretation of the study result Female subject of childbearing potential who is lactating or has positive urine pregnancy test at V0 or refuses to adop reliable method of contraception during the study.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: nitric oxide gel<br>st gel: sodium nitrites nd gel: maleic/ascorbic acids | Drug: nitric oxide gel<br>* st gel: sodium nitrites,BID local use X 28 days nd gel: maleic/ascorbic acids ,BID local use X 28 days<br>|
| Placebo Comparator: Placebo gel<br>st gel: phosphate-buffered saline nd gel: maleic/ascorbic acids | Drug: placebo gel<br>* placebo gel,BID local use X 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuopathic Pain Scale |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| vascular duplex parameters |  | 12 weeks | 
| the likelihood of reusing the nitric oxide gel recorded |  | 12weeks |