Effect of Resveratrol and Pharmacist Intervention on Diabetes Mellitus and Its Neuropathic Complication

Study Overview
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Brief Summary
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Management of symptoms associated with diabetic neuropathy is a difficult issue for clinicians since it usually does not respond to standard analgesics. Resveratrol is a naturally occurring plant-derived, polyphenolic compound, it exerts pleiotropic activity. The investigators believed that the implementation of multidisciplinary approaches including pharmacotherapy and provision of healthcare professional services such as pharmacist intervention are needed for alleviation of diabetic associated neuropathy.Therefore, the hypothesis of the present protocol is that the administration of resveratrol and/or provision of pharmaceutical care in patients with diabetic neuropathy might be of value in improving quality of life and managing diabetic neuropathic pain.The study is designed as a four-arm randomized, placebo-controlled clinical trial. Group one will be given only conventional hypoglycemic drugs. Group two patients will receive conventional hypoglycemic drugs accompanied by pharmacist interventions. Group three; patients will receive resveratrol 500 mg orally once daily after meals for three months, in addition to their regular hypoglycemic drugs. Group four; patients will receive resveratrol 500 mg orally once daily after meals along with their regular hypoglycemic drugs for a period of three months, accompanied by pharmacist interventions. Neuropathic pain will be measured by various neuropathic pain assessment tools. Nerve conduction studies will be performed to assess the effect of interventional therapy. The expected outcome will be the improvement of diabetic neuropathy associated symptoms along with glycemic status.

Detailed Description
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Diabetic neuropathy is the most common microvascular complication of diabetes, resulting from prolonged periods of hyperglycemia, damaging fragile nerve fibers and the walls of their blood vessels. Despite clinical developments in the treatment of diabetes complications, especially diabetic neuropathy, it still remains a clinical challenge with no effective solution. Conventional therapies such as anti-epileptics, opioid analgesics, and antidepressants for the treatment of neuropathic pain are quite challenging due to their serious adverse effects. There is a need to investigate novel effective and safe options. Recently, polyphenols have also been introduced as potential neuroprotective agents in diabetes. Alleviation of the symptoms associated with diabetic neuropathy and exerting preventive measures to halt the emergence of neuropathy complications are crucial priorities, and this requires multidisciplinary approaches including pharmacotherapy and provision of healthcare professional services such as pharmacist intervention. Aim of the study: to evaluate the effects of resveratrol and pharmaceutical care on the severity of diabetic neuropathy and improvement in the quality of life of diabetic patients. Study design: four-arm randomized, double-blind, placebo-controlled clinical trial. Interventions:Therapeutic intervention and Pharmacist intervention. Number of participants = 120 Number of groups = 4 groups each of 30 patients

Official Title
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Impact of Resveratrol and Pharmaceutical Care on Diabetes Mellitus and Its Neuropathic Complication

Conditions
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Diabetic Neuropathies

Intervention / Treatment
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* Drug: Resveratrol
* Drug: Placebo
* Other: Resveratrol plus Pharmaceutical care
* Other: Placebo+Pharmaceutical care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with pain due to bilateral peripheral neuropathy caused by type 2 diabetes mellitus. HbA1c of greater than 7% The daily pain must be present for at least 6 months, and the diagnosis will be confirmed by a score >4 on the Michigan Neuropathy Screening Instrument (MNSI), Douleur Neuropathique 4 (DN4). The severity of pain when evaluated for the past 24 was ≥4 on the 10 cm Visual Analogue Scale (VAS) at baseline without the use of analgesic for 48 hours. Exclusion Criteria: Older subjects with high risks of cardiovascular diseases, Pregnant or breastfeeding, Having a prior renal transplant or current renal dialysis, Patients have a diagnosis of major depressive disorder, generalized anxiety disorder, heavy alcohol drinkers, Significant hepatic or renal disease, Patients on antioxidant therapy, or pentoxyphylline within the last month.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 65 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
Interventional Model Description: Eligible patients assigned to either conventional hypoglycemic drugs without pharmaceutical care, or conventional hypoglycemic drugs accompanied with pharmacist interventions or patients will receive resveratrol 500 mg capsules orally once daily with their regular hypoglycemic drugs or resveratrol 500 mg capsule orally along with their regular hypoglycemic drugs for a period of three months, accompanied with pharmacist interventions.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Resveratrol<br>Interventional group, participants in this group are receiving Resveratrol 500mg capsule once daily for 3 months. | Drug: Resveratrol<br>* This group received resveratrol with the conventional therapy<br>|
| Placebo Comparator: Placebo<br>Non-interventional group, participants are receiving only Placebo once daily for 3 months. Placebo formulated as capsule match the color and size of the active comparator, | Drug: Placebo<br>* This group received placebo with the conventional therapy<br>|
| Other: Resveratrol plus Pharmaceutical care<br>Interventional group, participants in this group are receiving Resveratrol 500mg capsule once daily for 3 months with pharmaceutical care. | Other: Resveratrol plus Pharmaceutical care<br>* This group received Resveratrol with Pharmaceutical care in addition to the conventional therapy<br>|
| Other: Placebo with pharmaceutical care<br>Interventional group, participants are receiving placebo along with pharmaceutical care for 3 months. | Other: Placebo+Pharmaceutical care<br>* This group received placebo with Pharmaceutical care in addition to the conventional therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| visual analog scale (VAS) | to assess neuropathic pain, VAS scale ranges between 0-10 , 0 indicates no pain while 10 indicates severe pain. | up to 3 months | 
| Douleur Neuropathique 4 questionnaire (DN4) | to assess the severity of diabetic peripheral neuropathy. | up to 3 months | 
| The Michigan Neuropathy Screening Instrument (MNSI) | to assess the severity of diabetic peripheral neuropathy | up to 3 months | 
| Electroneurography | Motor nerve conduction velocity (m/s), sensory nerve conduction velocity(m/s) will be measured using surface electrodes. | up to 3 months | 
| Assessment of Quality of Life | using the RAND-36 health survey questionnaire | up to 3 months | 
| Serum neopterin levels | biochemical marker for peripheral neuropathy | up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean change in fasting blood glucose | to assess glycemic status | up to 3 months | 
| Mean change of glycated hemoglobin (HbA1c)-mmol/l | to assess glycemic status | up to 3 months | 
| Measurement of serum level of LDL, cholesterol, HDL, Triglyceride | to assess the effect of the interventions on metabolic changes | up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic neuropathy, Neuropathic pain, pharmaceutical care, Resveratrol